WorldWideScience

Sample records for 188re 177lu 51cr

  1. Monte Carlo Calculation of Radioimmunotherapy with (90)Y-, (177)Lu-, (131)I-, (124)I-, and (188)Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts.

    Science.gov (United States)

    Lucas, S; Feron, O; Gallez, B; Masereel, B; Michiels, C; Vander Borght, T

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like (131)I or (90)Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of (90)Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as (90)Y, (177)Lu, (131)I, (124)I, and (188)Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). (90)Y and (188)Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  2. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Directory of Open Access Journals (Sweden)

    S. Lucas

    2015-01-01

    Full Text Available Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP and normal tissue complication probability (NTCP curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC. 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases.

  3. Monte Carlo Calculation of Radioimmunotherapy with 90Y-, 177Lu-, 131I-, 124I-, and 188Re-Nanoobjects: Choice of the Best Radionuclide for Solid Tumour Treatment by Using TCP and NTCP Concepts

    Science.gov (United States)

    Lucas, S.; Feron, O.; Gallez, B.; Masereel, B.; Michiels, C.; Vander Borght, T.

    2015-01-01

    Radioimmunotherapy has shown that the use of monoclonal antibodies combined with a radioisotope like 131I or 90Y still remains ineffective for solid and radioresistant tumour treatment. Previous simulations have revealed that an increase in the number of 90Y labelled to each antibody or nanoobject could be a solution to improve treatment output. It now seems important to assess the treatment output and toxicity when radionuclides such as 90Y, 177Lu, 131I, 124I, and 188Re are used. Tumour control probability (TCP) and normal tissue complication probability (NTCP) curves versus the number of radionuclides per nanoobject were computed with MCNPX to evaluate treatment efficacy for solid tumours and to predict the incidence of surrounding side effects. Analyses were carried out for two solid tumour sizes of 0.5 and 1.0 cm radius and for nanoobject (i.e., a radiolabelled antibody) distributed uniformly or nonuniformly throughout a solid tumour (e.g., Non-small-cell-lung cancer (NSCLC)). 90Y and 188Re are the best candidates for solid tumour treatment when only one radionuclide is coupled to one carrier. Furthermore, regardless of the radionuclide properties, high values of TCP can be reached without toxicity if the number of radionuclides per nanoobject increases. PMID:26136812

  4. Preparation and Preliminary Evaluation of 177Lu-EDTMP

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    <正>The study on 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-EDTMP is possible to be an effective radiopharmaceutical for pain

  5. Compartmental and dosimetric studies of anti-CD20 labelled with {sup 188}Re; Estudo compartimental e dosimetrico do Anti-CD20 marcado com {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Kuramoto, Graciela Barrio

    2016-10-01

    The radioimmunotherapy (RIT) uses MAbs conjugated to radionuclides α or β{sup -} emitters, both for therapy. Your treatment is based on the irradiation and tumor destruction, preserving the normal organs as the excess radiation. Radionuclides β{sup -} emitters as {sup 131}I, {sup 90}Y, {sup 188}Re {sup 177}Lu and are useful for the development of therapeutic radiopharmaceuticals and, when coupled with MAb and Anti-CD20 it is important mainly for the treatment of non-Hodgkin's lymphomas (NHL). {sup 188}Re (E{sub β} = 2.12 MeV; E{sub γ} = 155 keV; t1/2 = 16.9 h) is an attractive radionuclide for RIT. However, {sup 188}Re can be obtained from a radionuclide generator of {sup 188}W/{sup 188}Re, commercially available, making it convenient for use in research and for clinical routine. The CR of IPEN has a project aimed at the production of radiopharmaceutical {sup 188}Re-Anti-CD20, where the radionuclide can be obtained from a generator system {sup 188}W/{sup 188}Re. With this proposed a study to assess the efficiency of this labeling technique for treatment in accordance compartmental and dosimetry. The objective of this study was to compare the marking of anti-CD20 MAb with {sup 188}Re with the marking of the antibody with {sup 90}Y, {sup 131}I, {sup 177}Lu and {sup 99m}Tc (for their similar chemical characteristics) and {sup 211}At, {sup 213}Bi, {sup 223}Ra and {sup 225}Ac); through the study of labeling techniques reported in literature, the proposal of a compartmental model to evaluate its pharmacokinetic and dosimetric studies, high interest for therapy. The result of the study shows a favorable kinetics for {sup 188}Re, by their physical and chemical characteristics compared to the other evaluated radionuclides. The compartment proposed study describes the metabolism of {sup 188}Reanti- CD20 through a compartment mammillary model, which by their pharmacokinetic analysis, performed compared to products emitters β{sup -131}I-labeled anti CD20, {sup 177

  6. Preparation and Biodistribution Evaluation in Mice of ~(177)Lu-DOTA-TOC

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    The study of 177Lu labeled radiopharmaceuticals for cancer therapy is fast emerging as an important part of nuclear medicine. 177Lu-labelling of DOTA derivatized peptide DOTA-TOC (Tyr3-Octreotide) was carried out and biodistribution of 177Lu-DOTA-TOC in normal

  7. Biokinetic study of free {sup 177}Lu in NIH mice

    Energy Technology Data Exchange (ETDEWEB)

    Villarreal Jimenez, V.; Crudo, J., E-mail: josierys@yahoo.com [Comision Nacional de Energia Atomica (CNEA), Buenos Aires (Argentina); Rojo, A.M.; Deluca, G.M. [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina)

    2008-07-01

    Full text: {sup 177}Lu has been identified, by the scientific community, as a radionuclide with interesting advantages compared with {sup 90}Y and other beta emitters used in nuclear medicine. This paper analyses the free {sup 177}Lu biokinetic behavior in NIH male mice from activity measurements performed by the Radiopharmacy Division of CNEA (Comision Nacional de Energia Atomica) in the frame of an IAEA (International Atomic Energy Agency) Coordinated Research Project. The study of experimental data is a previous condition that allows drawing the activity-time curves for organs and to know the biodistribution of {sup 177}Lu. The cumulated activity in organs of interest in NIH male mice are calculated and critical organs are identified. The organs selected for analysis in this paper are the liver, kidneys, spleen, stomach, intestine, lungs, skeleton and red marrow. The last one is estimated from the activity measured in blood based on a recognized method published by Sgouros (2000). The results has been extrapolated to human assuming the same biokinetic behaviour as mice being the applicability of the different extrapolation methods also discussed. The direct extrapolation from mice data was the method of election from a radiological protection point of view. The measurement procedures, the data processing, the extrapolation techniques and the analysis performed in this study will contribute as a basis for future research of this group in the area of antibodies and other radiopharmaceutical labeled with {sup 177}Lu. The cumulated activity calculated in each organ is relevant because it makes possible to perform the dose assessment through the application of appropriate dose coefficients. It is a necessary step in order to evaluate the toxicity risk that is required in a pre-clinical study. (author)

  8. {sup 188}Re-Labeled Radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Jae Min [Seoul National University, Seoul (Korea, Republic of)

    2001-10-01

    The search for an ideal radioisotope for radiotherapy continues. As a generator-produced radioisotope emitting both beta and gamma rays with a short physical half-life of 16.9 hr, {sup 188}Re is an excellent candidate for radiotherapy. Its applications include the irradiation of coronary artery to prevent restenosis, treatment of rheumatoid arthritis, treatment of peritoneal effusion. palliation of metastatic bone pain, and treatment of liver cancer.

  9. Production of {sup 186}Re and {sup 188}Re, and synthesis of {sup 188}Re-DTPA

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kazuyuki; Motoishi, Shoji; Kobayashi, Katsutoshi; Izumo, Mishiroku [Department of Radioisotopes, Japan Atomic Energy Research Institute, Tokai, Ibaraki (Japan); Musdja, Muhammad Yanis

    1999-08-01

    Production of radioactive rhenium isotopes {sup 186}Re and {sup 188}Re, and synthesis of {sup 188}Re-DTPA have been studied. For {sup 186}Re, a production method by the {sup 185}Re(n, {gamma}) {sup 186}Re reaction in a reactor has been established. For {sup 188}Re, a production method by the double neuron capture reaction of {sup 186}W, which produces a {sup 188}W/{sup 188}Re generator, has been established. For synthesis of {sup 188}Re-DTPA, the optimum conditions, including pH, the amounts of regents and so on, have been determined. (author)

  10. [{sup 177}Lu]DOTA-anti-CD20: Labeling and pre-clinical studies

    Energy Technology Data Exchange (ETDEWEB)

    Audicio, Paola F., E-mail: paudicio@cin.edu.u [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Castellano, Gustavo, E-mail: gcas@famaf.unc.edu.a [FaMAF, Universidad Nacional de Cordoba, Ciudad Universitaria, 5016 Cordoba (Argentina); Tassano, Marcos R.; Rezzano, Maria E.; Fernandez, Marcelo [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay); Riva, Eloisa [Clinica Hematologica ' Prof. Dra. L. Diaz' , Hospital de Clinicas. Av. Italia. sn, Montevideo (Uruguay); Robles, Ana; Cabral, Pablo; Balter, Henia; Oliver, Patricia [Departamento de Radiofarmacia, Centro de Investigaciones Nucleares, Facultad de Ciencias, Universidad de la Republica, Mataojo 2055, 11400 Montevideo (Uruguay)

    2011-07-15

    Anti-CD20 (Rituximab), a specific chimeric monoclonal antibody used in CD20-positive Non-Hodgkin's Lymphoma, was conjugated to a bifunctional quelate (DOTA) and radiolabeled with {sup 177}Lu through a simple method. [{sup 177}Lu]-DOTA-anti-CD20 was obtained with a radiochemical purity higher than 97%, and showed good chemical and biological stability, maintaining its biospecificity to CD20 antigens. Monte Carlo simulation showed high doses deposited on a spheroid tumor mass model. This method seems to be an appropriate alternative for the production of [{sup 177}Lu]-DOTA-anti-CD20 as therapeutic radiopharmaceutical.

  11. Development of 177Lu-phytate Complex for Radiosynovectomy

    Directory of Open Access Journals (Sweden)

    Hassan Yousefnia

    2013-05-01

    Full Text Available Objective(s: In this work a new possible agent for radiosynovectomy has been targeted for articular pain palliation. Materials and Methods: Lu-177 of 2.6-3 GBq/mg specific activity was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4 × 1013 n.cm-2.s-1. The product was converted into chloride form which was further used for labeling of 177Lu-phytate complex and checked using ITLC (MeOH: H2O: acetic acid, 4: 4: 2, as mobile phase. The complex stability and viscosity were checked in the final solution up to seven days. The prepared complex solution (100 µCi/100 µl was injected intra-articularly to male rat knee joint. Leakage of radioactivity from injection site and its distribution in organs were investigated up to seven days. Results: The complex was successfully prepared with high radiochemical purity (>99.9 %. Approximately, the whole injected dose has remained in injection site seven days after injection. Conclusion: The complex was proved to be a feasible agent for cavital radiotherapy in oncology and rheumatology

  12. Synthesis of {sup 188}Re-DMSA complex using carrier-free {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Kazuyuki; Izumo, Mishiroku [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment; Islam, M.S.

    1997-03-01

    The synthesis of rhenium-DMSA labelled compound using carrier-free {sup 188}Re from the {sup 188}W/{sup 188}Re generator has been carried out. Stannous chloride was used as the reducing agent for reduction of rhenium and ascorbic acid was used as an antioxidant in the reaction media. The dependence of the yield of Re-DMSA complex upon the concentration of reducing agent, pH, reaction time, anti-oxidant, carrier and temperature was investigated. Under optimum conditions, the yield of Re-DMSA complexes were more than 98% for the carrier-free as well as carrier-added {sup 188}Re. The stability of the Re-DMSA complexes at different pH and time were also investigated. It was found that the Re-DMSA complex was very stable and did not undergo any changes or decomposition with the changes of pH from its initial values even after 48 hours of pH change for carrier-free as well as carrier-added complexes. (author)

  13. Radiolabeling parameters of {sup 177}Lu-DOTA-RITUXIMAB

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de, E-mail: adriana.avfernandes@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-07-01

    Cancer treatment using radioimmunotherapy (RIT) has been the focus of much research in the last two decades. In RIT, a radioisotope is coupled to a monoclonal antibody (mAb) to form a tumor-specific target agent to improve the cytocidal effect of the mAbs. RIT allows the systemic delivery of radiation to disease target by mAbs while sparing normal tissues. Rituximab® (Mabthera - Roche) is a chimeric mouse-human monoclonal antibody; it selectively binds with high affinity to the CD20 antigen, a hydrophobic transmembrane protein, which is expressed on B-lymphocytes and in more than 90% of B cell non-Hodgkin's lymphomas (NHL). The conjugation and radiolabeling process involve special conditions of pH and temperature, long processes of manipulation and mixing. All this process can damage the antibody structure and compromise its clinical application. Therefore, these parameters must be largely studied. The aim of this work was to evaluate the best radiolabeling conditions of DOTA-rituximab. Briefly, 10 mg of antibody previously purified by ultrafiltration device was conjugated with DOTA-NHS-ester (Macrocyclics) in 50 fold molar excess. The reaction was conducted for 1 hour in phosphate buffer pH 8.0 and gently mixing at room temperature, remaining for 24 hours under refrigeration. The immunoconjugated was purified by size exclusion column and ultrafiltration device. The radiolabeled parameters studied were: immunoconjugated mass, activity of {sup 177}LuCl{sub 3}, reaction time, temperature and pH. The radiochemical purity of the preparations was determined using analysis by thin layer chromatography (TLC-SG plates). The best studied condition presented radiochemical purity above 95% and the integrity of antibody was preserved. (author)

  14. 188W/188Re Generator System and Its Therapeutic Applications

    Directory of Open Access Journals (Sweden)

    A. Boschi

    2014-01-01

    Full Text Available The 188Re radioisotope represents a useful radioisotope for the preparation of radiopharmaceuticals for therapeutic applications, particularly because of its favorable nuclear properties. The nuclide decay pattern is through the emission of a principle beta particle having 2.12 MeV maximum energy, which is enough to penetrate and destroy abnormal tissues, and principle gamma rays (Eγ=155 keV, which can efficiently be used for imaging and calculations of radiation dose. 188Re may be conveniently produced by 188W/188Re generator systems. The challenges related to the double neutron capture reaction route to provide only modest yield of the parent 188W radionuclide indeed have been one of the major issues about the use of 188Re in nuclear medicine. Since the specific activity of 188W used in the generator is relatively low (<185 GBq/g, the eluted Re188O4- can have a low radioactive concentration, often ineffective for radiopharmaceutical preparation. However, several efficient postelution concentration techniques have been developed, which yield clinically useful Re188O4- solutions. This review summarizes the technologies developed for the preparation of 188W/188Re generators, postelution concentration of the 188Re perrhenate eluate, and a brief discussion of new chemical strategies available for the very high yield preparation of 188Re radiopharmaceuticals.

  15. Potential therapeutic radiotracers: preparation, biodistribution and metabolic characteristics of 177Lu-labeled cyclic RGDfK dimer.

    Science.gov (United States)

    Shi, Jiyun; Liu, Zhaofei; Jia, Bing; Yu, Zilin; Zhao, Huiyun; Wang, Fan

    2010-06-01

    In this study, we reported the preparation and evaluation of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2 (RGD2 = E[c(RGDfK)](2)) as a potential therapeutic radiotracers for the treatment of integrin alpha(v)beta(3)-positive tumors. The BALB/c nude mice bearing the U87MG human glioma xenografts were used to evaluate the biodistribution characteristics and excretion kinetics of (177)Lu-DOTA-RGD2, (177)Lu-DOTA-Bz-RGD2 and (177)Lu-DTPA-Bz-RGD2. It was found that there were no major differences in their lipophilicity and biodistribution characteristics, particularly at latter time points. A major advantage of using DTPA-Bz as the bifunctional chelator (BFC) was its high radiolabeling efficiency (fast and high yield radiolabeling) at room temperature. Using DOTA and DOTA-Bz as BFCs, the radiolabeling kinetics was slow, and heating at 100 degrees C and higher DOTA-conjugate concentration were needed for successful (177)Lu-labeling. Therefore, DTPA-Bz is an optimal BFC for routine preparation of (177)Lu-labeled cyclic RGDfK peptides, and (177)Lu-DTPA-Bz-RGD2 is worthy of further investigation for targeted radiotherapy of integrin alpha(v)beta(3)-positive tumors.

  16. Standardization and measurement of gamma-ray probability per decay of 177Lu.

    Science.gov (United States)

    Dias, Mauro S; Silva, Fabrício F V; Koskinas, Marina F

    2010-01-01

    The procedure followed by the Nuclear Metrology Laboratory (LMN), at the Nuclear and Energy Research Institute (IPEN), for the primary standardization of (177)Lu is described. This radionuclide is widely used in radiopharmacy due to its convenient half-life and emitted beta ray energies. The (177)Lu solution was supplied during an international comparison sponsored by BIPM in 2009 and the primary standardization has been accomplished by the 4pibeta-gamma coincidence method using a proportional counter in 4pi geometry coupled with two NaI(Tl) scintillation counters. The beta efficiency was varied by placing Collodion and aluminum absorbers over and under the radioactive source. The (177)Lu calibrated sources were also measured in a previously calibrated HPGe spectrometer, in order to obtain the emission probability per decay for the selected gamma-ray transitions. The experimental extrapolation curves were also compared with Monte Carlo simulations by means of code ESQUEMA developed at the LMN.

  17. Toxicity of trastuzumab labeled {sup 177}Lu on MCF7 and SKBr3 cell lines

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Hossein Babaei, Mohammad; Johari Daha, Fariba [Department of Radioisotope, Nuclear Science and Technology Research Institute, Tehran (Iran, Islamic Republic of)

    2010-10-15

    In this study, we labeled trastuzumab with {sup 177}Lu to synthesize a new radiopharmaceutical for therapy of breast cancer and at the first stage investigated its therapeutic effects on SKBr3 and MCF7 breast cancer cell lines. Trastuzumab-{sup 177}Lu showed very good in-vitro characteristics such as high radiochemical purity (91{+-}0.9%), good stability in PBS buffer (86{+-}2.3%) and blood serum (81{+-}2.7%) up to 96 h, appropriate immunoreactivity (85.4{+-}1.1%) and high cytotoxicity in HER2 expression cells. 5 fold increase in toxicity of trastuzumab-{sup 177}Lu was observed when compared with unlabeled trastuzumab on SKBr3 cells.

  18. [177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.

    Science.gov (United States)

    Sundberg, Asa Liljegren; Gedda, Lars; Orlova, Anna; Bruskin, Alexander; Blomquist, Erik; Carlsson, Jörgen; Tolmachev, Vladimir

    2004-04-01

    Patients with glioblastoma multiforme have a poor prognosis due to recurrences originating from spread cells. The use of radionuclide targeting might increase the chance of inactivating single tumor cells with minimal damage to surrounding healthy tissue. As a target, overexpressed epidermal growth factor receptors (EGFR) may be used. A natural ligand to EGFR, the epidermal growth factor (EGF) is an attractive targeting agent due to its low molecular weight (6 kDa) and high affinity for EGFR. 177Lu (T(1/2) = 6.7 days) is a radionuclide well suited for treatment of small tumor cell clusters, since it emits relatively low-energy beta particles. The goal of this study was to prepare and preclinically evaluate both in vitro and in vivo the [177Lu]Bz-DTPA-EGF conjugate. The conjugate was characterized in vitro for its cell-binding properties, and in vivo for its pharmacokinetics and ability to target EGFR. [177Lu]Bz-DTPA-EGF bound to cultured U343 glioblastoma cells with an affinity of 1.9 nM. Interaction with EGFR led to rapid internalization, and more than 70% of the cell-associated radioactivity was internalized after 30 minutes of incubation. The retention of radioactivity was good, with more than 65% of the 177Lu still cell-associated after 2 days. Biodistribution studies of i.v. injected [177Lu]Bz-DTPA-EGF in NMRI mice demonstrated a rapid blood clearance. Most of the radioactivity was found in the liver and kidneys. The liver uptake was receptor-mediated, since it could be significantly reduced by preinjection of unlabeled EGF. In conclusion, [177Lu]Bz-DTPA-EGF seems to be a promising candidate for locoregional treatment of glioblastoma due to its high binding affinity, low molecular weight, and ability to target EGFR in vivo.

  19. Esthesioneuroblastoma (olfactory neuroblastoma) treated with 111In-octreotide and 177Lu-DOTATATE PRRT.

    Science.gov (United States)

    Makis, William; McCann, Karey; McEwan, Alexander J B

    2015-04-01

    A 51-year-old man with a recurrent metastatic esthesioneuroblastoma (olfactory neuroblastoma) was referred for peptide receptor radionuclide therapy (PRRT). He received 4 treatments of 111In-octreotide over 8 months and 3 treatments of 177Lu-DOTATATE over 4 months, which helped alleviate his symptoms and improved his quality of life; however, the tumor ultimately progressed and he passed away shortly thereafter. PRRT with 111In-octreotide or 177Lu-DOTATATE could play a role in the management of esthesioneuroblastoma.

  20. Pretargeted 177Lu radioimmunotherapy of carcinoembryonic antigen-expressing human colonic tumors in mice.

    NARCIS (Netherlands)

    Schoffelen, R.; Graaf, W.T.A. van der; Franssen, G.M.; Sharkey, R.M.; Goldenberg, D.M.; McBride, W.J.; Rossi, E.A.; Eek, A.; Oyen, W.J.G.; Boerman, O.C.

    2010-01-01

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies in combination with a radiolabeled peptide reduces the radiation dose to normal tissues, especially the bone marrow. In this study, the optimization, therapeutic efficacy, and toxicity of PRIT of colon cancer with a (177)Lu-labeled pep

  1. Preparation and Characterization of {sup 177}Lu Labeled Antibody against Tyrosine Kinase Receptor Her2

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So-Young; Hong, Young-Don; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-05-15

    The tyrosine kinase receptor Her2, also known in humans as erbB2, is a member of the epidermal growth factor receptor (EGFR or erbB1) family. The Her2 is highly expressed in many cancer types and over expressed in approximately 30% of all primary breast cancer. Overexpression of Her2 is associated with a poor prognosis. Her2 is a suitable target because it involves an extracellular domain that can be targeted by antibodies produced by B cells. Based on these advantages, we tried to prepare the {sup 177}Lu labeled Her2 antibody. This radioimmunoconjugate could act by not only blocking the Her2 signalling pathway using antibody but also killing the tumour cell using {beta} energy of {sup 177}Lu.

  2. Quantitative (177)Lu SPECT imaging using advanced correction algorithms in non-reference geometry.

    Science.gov (United States)

    D'Arienzo, M; Cozzella, M L; Fazio, A; De Felice, P; Iaccarino, G; D'Andrea, M; Ungania, S; Cazzato, M; Schmidt, K; Kimiaei, S; Strigari, L

    2016-12-01

    Peptide receptor therapy with (177)Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of (177)Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher (177)Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using μ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of (177)Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators.

  3. In Vivo Measurement and Characterization of a Novel Formulation of [177Lu]-DOTA-Octreotate

    Directory of Open Access Journals (Sweden)

    Dale Bailey

    2016-01-01

    Full Text Available Objective(s:Lutetium-177 can be made with high specific activity and with no other isotopes of lutetium present, referred to as “No Carrier Added” (NCA 177Lu. We have radiolabelled DOTA-conjugated peptide DOTA‐(Tyr3‐octreotate with NCA 177Lu (“NCA-LuTATE” and used it in nearly 40 therapeutic administrations for subjects with neuroendocrine tumours or meningiomas. In this paper, we report on our initial studies on aspects of the biodistribution and dosimetry of NCA-LuTATE from gamma camera 2D whole body (WB and quantitative 3D SPECT (qSPECT 177Lu imaging. Methods: Thirteen patients received 39 NCA-LuTATE injections. Extensive WB planar and qSPECT imaging was acquired at approximately 0.5, 4, 24 and 96 h to permit estimates of clearance and radiation dose estimation using MIRD-based methodology (OLINDA-EXM. Results:The average amount of NCA-Lutate administered per cycle was 7839±520 MBq. Bi-exponential modelling of whole body clearance showed half lives for the fast & slow components of t½=2.1±0.6 h and t½=58.1±6.6 h respectively. The average effective dose to kidneys was 3.1±1.0 Gy per cycle. In eight patients completing all treatment cycles the average total dose to kidneys was 11.7±3.6 Gy. Conclusions: We have shown that NCA-LuTATE has an acceptable radiation safety profile and is a suitable alternative to Carrier-Added 177Lu formulations. The fast component of the radiopharmaceutical clearance was closely correlated with baseline renal glomerular filtration rate, and this had an impact on radiation dose to the kidneys. In addition, it has less radioactive waste issues and requires less peptide per treatment.

  4. Subacute haematotoxicity after PRRT with {sup 177}Lu-DOTA-octreotate: prognostic factors, incidence and course

    Energy Technology Data Exchange (ETDEWEB)

    Bergsma, Hendrik; Konijnenberg, Mark W.; Kam, Boen L.R.; Teunissen, Jaap J.M.; Kooij, Peter P.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Franssen, Gaston J.H.; Eijck, Casper H.J. van [Erasmus Medical Center, Department of Surgery, Rotterdam (Netherlands)

    2016-03-15

    In peptide receptor radionuclide therapy (PRRT), the bone marrow (BM) is one of the dose-limiting organs. The accepted dose limit for BM is 2 Gy, adopted from {sup 131}I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients treated with PRRT with {sup 177}Lu-DOTA{sup 0}-Tyr{sup 3}-octreotate ({sup 177}Lu-DOTATATE). Also, absorbed BM dose estimates were evaluated and compared with the accepted 2 Gy dose limit. The incidence and duration of grade 3 or 4 haematological toxicity (according to CTCAE v3.0) and risk factors were analysed. Mean BM dose per unit (gigabecquerels) of administered radioactivity was calculated and the correlations between doses to the BM and haematological risk factors were determined. Haematological toxicity (grade 3/4) occurred in 34 (11 %) of 320 patients. In 15 of the 34 patients, this lasted more than 6 months or blood transfusions were required. Risk factors significantly associated with haematological toxicity were: poor renal function, white blood cell (WBC) count <4.0 x 10{sup 9}/l, age over 70 years, extensive tumour mass and high tumour uptake on the OctreoScan. Previous chemotherapy was not associated. The mean BM dose per administered activity in 23 evaluable patients was 67 ± 7 mGy/GBq, resulting in a mean BM dose of 2 Gy in patients who received four cycles of 7.4 GBq {sup 177}Lu-DOTATATE. Significant correlations between (cumulative) BM dose and platelet and WBC counts were found in a selected group of patients. The incidence of subacute haematological toxicity after PRRT with {sup 177}Lu-DOTATATE is acceptable (11 %). Patients with impaired renal function, low WBC count, extensive tumour mass, high tumour uptake on the OctreoScan and/or advanced age are more likely to develop grade 3/4 haematological toxicity. The BM dose limit of 2 Gy, adopted from {sup 131}I, seems not to be valid for PRRT with {sup 177}Lu-DOTATATE. (orig.)

  5. Gamma camera calibration and validation for quantitative SPECT imaging with (177)Lu.

    Science.gov (United States)

    D'Arienzo, M; Cazzato, M; Cozzella, M L; Cox, M; D'Andrea, M; Fazio, A; Fenwick, A; Iaccarino, G; Johansson, L; Strigari, L; Ungania, S; De Felice, P

    2016-06-01

    Over the last years (177)Lu has received considerable attention from the clinical nuclear medicine community thanks to its wide range of applications in molecular radiotherapy, especially in peptide-receptor radionuclide therapy (PRRT). In addition to short-range beta particles, (177)Lu emits low energy gamma radiation of 113keV and 208keV that allows gamma camera quantitative imaging. Despite quantitative cancer imaging in molecular radiotherapy having been proven to be a key instrument for the assessment of therapeutic response, at present no general clinically accepted quantitative imaging protocol exists and absolute quantification studies are usually based on individual initiatives. The aim of this work was to develop and evaluate an approach to gamma camera calibration for absolute quantification in tomographic imaging with (177)Lu. We assessed the gamma camera calibration factors for a Philips IRIX and Philips AXIS gamma camera system using various reference geometries, both in air and in water. Images were corrected for the major effects that contribute to image degradation, i.e. attenuation, scatter and dead- time. We validated our method in non-reference geometry using an anthropomorphic torso phantom provided with the liver cavity uniformly filled with (177)LuCl3. Our results showed that calibration factors depend on the particular reference condition. In general, acquisitions performed with the IRIX gamma camera provided good results at 208keV, with agreement within 5% for all geometries. The use of a Jaszczak 16mL hollow sphere in water provided calibration factors capable of recovering the activity in anthropomorphic geometry within 1% for the 208keV peak, for both gamma cameras. The point source provided the poorest results, most likely because scatter and attenuation correction are not incorporated in the calibration factor. However, for both gamma cameras all geometries provided calibration factors capable of recovering the activity in

  6. A study on indirect radiolabeling of IgG with carrier free 188Re

    Institute of Scientific and Technical Information of China (English)

    2003-01-01

    188Re labeled monoclonal antibodies are potential candidates for use in radioimmunotherapy. S-Bz-MAG3 as a bifunctional chelating agent was used for labeling of IgG with carrier free 188Re by pre-radiolabeling of the chelating approach. The conjugation conditions were optimized. The stability of 188Re-MAG3-IgG in vitro was high. The results may be useful to the studies of 188Re labeled MAbs for radioimmunotherapy.

  7. DNA damage in blood lymphocytes in patients after {sup 177}Lu peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Eberlein, Uta; Bluemel, Christina; Buck, Andreas Konrad; Werner, Rudolf Alexander; Lassmann, Michael [University of Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Nowak, Carina; Scherthan, Harry [Bundeswehr Institute of Radiobiology affiliated to the University of Ulm, Munich (Germany)

    2015-10-15

    The aim of the study was to investigate DNA double strand break (DSB) formation and its correlation with the absorbed dose to the blood lymphocytes of patients undergoing their first peptide receptor radionuclide therapy (PRRT) with {sup 177}Lu-labelled DOTATATE/DOTATOC. The study group comprised 16 patients receiving their first PRRT. At least six peripheral blood samples were obtained before, and between 0.5 h and 48 h after radionuclide administration. From the time-activity curves of the blood and the whole body, residence times for blood self-irradiation and whole-body irradiation were determined. Peripheral blood lymphocytes were isolated, fixed with ethanol and subjected to immunofluorescence staining for colocalizing γ-H2AX/53BP1 DSB-marking foci. The average number of DSB foci per cell per patient sample was determined as a function of the absorbed dose to the blood and compared with an in vitro calibration curve established in our laboratory with {sup 131}I and {sup 177}Lu. The average number of radiation-induced foci (RIF) per cell increased over the first 5 h after radionuclide administration and decreased thereafter. A linear fit from 0 to 5 h as a function of the absorbed dose to the blood agreed with our in vitro calibration curve. At later time-points the number of RIF decreased, indicating progression of DNA repair. Measurements of RIF and the absorbed dose to the blood after systemic administration of {sup 177}Lu may be used to obtain data on the individual dose-response relationships in vivo. Individual patient data were characterized by a linear dose-dependent increase and an exponential decay function describing repair. (orig.)

  8. (90) Y/(177) Lu-labelled Cetuximab immunoconjugates: radiochemistry optimization to clinical dose formulation.

    Science.gov (United States)

    Chakravarty, Rubel; Chakraborty, Sudipta; Sarma, Haladhar Dev; Nair, K V Vimalnath; Rajeswari, Ardhi; Dash, Ashutosh

    2016-07-01

    Radiolabelled monoclonal antibodies (mAbs) are increasingly being utilized in cancer theranostics, which is a significant move toward tailored treatment for individual patients. Cetuximab is a recombinant, human-mouse chimeric IgG1 mAb that binds to the epidermal growth factor receptor with high affinity. We have optimized a protocol for formulation of clinically relevant doses (~2.22 GBq) of (90) Y-labelled Cetuximab and (177) Lu-labelled Cetuximab by conjugation of the mAb with a suitable bifunctional chelator, N-[(R)-2-amino-3-(paraisothiocyanato-phenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-N,N,N',N″,N″-pentaacetic acid (CHX-A″-DTPA). The radioimmunoconjugates demonstrated reasonably high specific activity (1.26 ± 0.27 GBq/mg for (90) Y-CHX-A″-DTPA-Cetuximab and 1.14 ± 0.15 GBq/mg for (177) Lu-CHX-A″-DTPA-Cetuximab), high radiochemical purity (>95%) and appreciable in vitro stability under physiological conditions. Preliminary biodistribution studies with both (90) Y-CHX-A″-DTPA-Cetuximab and (177) Lu-CHX-A″-DTPA-Cetuximab in Swiss mice bearing fibrosarcoma tumours demonstrated significant tumour uptake at 24-h post-injection (p.i.) (~16%ID/g) with good tumour-to-background contrast. The results of the biodistribution studies were further corroborated by ex vivo Cerenkov luminescence imaging after administration of (90) Y-CHX-A″-DTPA-Cetuximab in tumour-bearing mice. The tumour uptake at 24 h p.i. was significantly reduced with excess unlabelled Cetuximab, suggesting that the uptake was receptor mediated. The results of this study hold promise, and this strategy should be further explored for clinical translation.

  9. {sup 177}Lu-DOTMP: a viable agent for palliative radiotherapy of painful bone metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Das, T.; Chakraborty, S.; Banerjee, S. [Radiopharmaceuticals Div., Bhabha Atomic Research Centre, Mumbai (India); Sarma, H.D. [Radiation Biology and Health Sciences Div., Bhabha Atomic Research Centre, Mumbai (India)

    2008-07-01

    The suitable nuclear decay characteristics [T{sub 1/2} = 6.73 d, E{sub {beta}}{sub (max)} = 497 keV, E{sub {gamma}} = 113 keV (6.4%), 208 keV (11%)] as well as the feasibility of large-scale production with adequate specific activity and radionuclidic purity using a moderate flux reactor are important attributes towards {sup 177}Lu to be considered as a promising radionuclide for palliative care in painful bone metastasis. The present study describes the preparation of {sup 177}Lu complex of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetramethylene phosphonic acid (DOTMP) and its preliminary biological evaluation in animal models with an aim to proposing it as a viable radiopharmaceutical for bone pain palliation. The choice DOTMP as the polyaminophosphonic acid carrier ligand is based on the enhanced thermodynamic stability and kinetic inertness of the metal-ligand complexes with macrocyclic chelators. {sup 177}Lu was produced with a specific activity of {proportional_to} 12 GBq/mg ({proportional_to} 324 mCi/mg) and radionuclidic purity of 99.98% by irradiation of natural Lu{sub 2}O{sub 3} target at a thermal neutron flux of {proportional_to} 6 x 10{sup 13} n/cm{sup 2} s for 21 d. {sup 177}Lu-DOTMP complex was prepared in high yield and excellent radiochemical purity (> 99%) using DOTMP synthesized and characterized in-house. The complex exhibited excellent in-vitro stability at room temperature. Biodistribution studies in Wistar rats showed rapid skeletal accumulation of the injected activity [(1.60{+-}0.19)% per gram in femur at 3 h post-injection] with fast clearance from blood and minimal uptake in any of the major organs. Scintigraphic studies carried out in normal Wistar rats and New Zealand white rabbits also demonstrated significant accumulation of the agent in skeleton and almost no retention in any other vital organs. (orig.)

  10. 177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Giusti, Anna Maria; Riccardi, Elena; Bruland, Øyvind S.; Selbo, Pål Kristian; Dahle, Jostein

    2014-01-01

    Background CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia cells (CLL). The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC) 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin). The present toxicity study was performed prior to initiation of clinical studieswith 177Lu-HH1. Methodology/Principal Findings Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group. Conclusions/Significance 177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients. PMID:25068508

  11. 177Lu-DOTA-HH1, a novel anti-CD37 radio-immunoconjugate: a study of toxicity in nude mice.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available CD37 is an internalizing B-cell antigen expressed on Non-Hodgkin lymphoma (NHL and chronic lymphocytic leukemia cells (CLL. The anti-CD37 monoclonal antibody HH1 was conjugated to the bifunctional chelator p-SCN-Bn-DOTA and labelled with the beta-particle emitting radionuclide 177Lu creating the radio-immunoconjugate (RIC 177Lu-DOTA-HH1 (177Lu-HH1, trade name Betalutin. The present toxicity study was performed prior to initiation of clinical studies with 177Lu-HH1.Nude mice with or without tumor xenografts were treated with 50 to 1000 MBq/kg 177Lu- HH1 and followed for clinical signs of toxicity up to ten months. Acute, life threatening bone marrow toxicity was observed in animals receiving 800 and 1000 MBq/kg 177Lu-HH1. Significant changes in serum concentrations of liver enzymes were evident for treatment with 1000 MBq/kg 177Lu-HH1. Lymphoid depletion, liver necrosis and atrophy, and interstitial cell hyperplasia of the ovaries were also observed for mice in this dose group.177Lu-DOTA-HH1 was well tolerated at dosages about 10 times above those considered relevant for radioimmunotherapy in patients with B-cell derived malignancies.The toxicity profile was as expected for RICs. Our experimental results have paved the way for clinical evaluation of 177Lu-HH1 in NHL patients.

  12. Realistic multi-cellular dosimetry for 177Lu-labelled antibodies: model and application

    Science.gov (United States)

    Marcatili, S.; Pichard, A.; Courteau, A.; Ladjohounlou, R.; Navarro-Teulon, I.; Repetto-Llamazares, A.; Heyerdahl, H.; Dahle, J.; Pouget, J. P.; Bardiès, M.

    2016-10-01

    Current preclinical dosimetric models often fail to take account of the complex nature of absorbed dose distribution typical of in vitro clonogenic experiments in targeted radionuclide therapy. For this reason, clonogenic survival is often expressed as a function of added activity rather than the absorbed dose delivered to cells/cell nuclei. We designed a multi-cellular dosimetry model that takes into account the realistic distributions of cells in the Petri dish, for the establishment of survival curves as a function of the absorbed dose. General-purpose software tools were used for the generation of realistic, randomised 3D cell culture geometries based on experimentally determined parameters (cell size, cell density, cluster density, average cluster size, cell cumulated activity). A mixture of Monte Carlo and analytical approaches was implemented in order to achieve as accurate as possible results while reducing calculation time. The model was here applied to clonogenic survival experiments carried out to compare the efficacy of Betalutin®, a novel 177Lu-labelled antibody radionuclide conjugate for the treatment of non-Hodgkin lymphoma, to that of 177Lu-labelled CD20-specific (rituximab) and non-specific antibodies (Erbitux) on lymphocyte B cells. The 3D cellular model developed allowed a better understanding of the radiative and non-radiative processes associated with cellular death. Our approach is generic and can also be applied to other radiopharmaceuticals and cell distributions.

  13. Preparation and biological evaluation of {sup 177}Lu conjugated PR81 for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Salouti, Mojtaba, E-mail: saloutim@yahoo.com [Department of Biology, Faculty of Sciences, Zanjan Branch, Islamic Azad University, Zanjan 45156-58145 (Iran, Islamic Republic of); Babaei, Mohammad Hossein [Nuclear Biomolecule Laboratory, Radioisotope Department, Nuclear Science and Technology Research Institute, Tehran 14144-1339 (Iran, Islamic Republic of); Rajabi, Hossein [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of); Rasaee, Mohammad javad [Department of Medical Biotechnology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran 14115-111 (Iran, Islamic Republic of)

    2011-08-15

    Aim: PR81 is a monoclonal antibody that binds with high affinity to MUC1 antigen that is over expressed in 80% of breast cancers. In this study, we developed a method for indirect labeling of PR81 with lutetium-177 and performed all preclinical qualifications in production of a biologic agent for radioimmunotherapy of breast cancer. Materials and Methods: The radiochemical purity and in vitro stability of {sup 177}Lu labeled PR81 was determined by instant thin layer chromatography. The immunoreactivity and cell toxicity of the complex were tested on MCF7 cell line. The biodistribution and scintigraphy studies were performed in BALB/c mice with breast tumor. Results: The radiochemical purity was 91.2{+-}3.8% after 2 h. The in vitro stabilities in phosphate buffer and human blood serum were 83.1{+-}3.4% and 76.2{+-}3.6% at 96 h, respectively. The immunoreactivity of the complex was 83.4{+-}2.4%. The cell toxicity study showed that the complex inhibited 85.2{+-}3.4% growth of MCF7 cells at a concentration of 2500 ng/ml after 96 h. The biodistribution and scintigraphy studies showed the accumulation of the complex at the site of tumors with high sensitivity and specificity. Conclusion: The results showed that one may consider {sup 177}Lu-DOTA-PR81 as a potential radiopharmaceutical for therapy of human breast cancer, which needs further investigations.

  14. Reducing Renal Uptake of {sup 177}Lu Labeled CCK Derivative using Basic Amino Acids

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Soyoung; Lim, Jaecheong; Joh, Eunha [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    Radiolabeled peptides have been designed to target the relative receptors overespressed in tumor cells, such as integrin αvβ3, gastrin-releasing peptide receptor (GRPR), melanocortin-1 receptor (MC1-R), glucagon-like peptide-a receptor (GLP-1R), and cholecystokinin (CCK) receptor. Most of these peptides are eliminated from the body via the kidney and are partly reabsorbed in the proximal tubular cells. However, the high renal uptake of the radiolabeled peptides may lead to renal toxicity. In this study we investigated various amino acid solutions to reduce the renal uptake of {sup 177}Lu-DOTA-CCK derivative. Renal uptake of {sup 177}Lu-DOTA-CCK derivative is effectively reduced by the administration of positively charged amino acids. The administration of 12 mg of L-lysine was as effective in reducing the renal uptake as 6 mg of lysine and 6 mg of arginine combinations. Further studies will be performed to identify the most potent inhibitor of renal reuptake of radiolabeled peptides and minimize the chance of unwanted side effects.

  15. Comparative Efficacy of 177Lu and 90Y for Anti-CD20 Pretargeted Radioimmunotherapy in Murine Lymphoma Xenograft Models

    Energy Technology Data Exchange (ETDEWEB)

    Frost, Sophia; Frayo, Shani; Miller, Brian W.; Orozco, Johnnie J.; Booth, Garrett C.; Hylarides, Mark; Lin, Yukang; Green, Damian J.; Gopal, Ajay K.; Pagel, John M.; Back, Tom; Fisher, Darrell R.; Press, Oliver W.

    2015-03-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice.

  16. Evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab as a radioimmunotherapy agent targeting VEGF expressing cancers.

    Science.gov (United States)

    Kameswaran, Mythili; Pandey, Usha; Gamre, Naresh; Vimalnath, K V; Sarma, Haladhar Dev; Dash, Ashutosh

    2016-08-01

    This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF.

  17. Multispecies animal investigation on biodistribution, pharmacokinetics and toxicity of {sup 177}Lu-EDTMP, a potential bone pain palliation agent

    Energy Technology Data Exchange (ETDEWEB)

    Mathe, Domokos [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)], E-mail: mdomokos@hp.osski.hu; Balogh, Lajos; Polyak, Andras; Kiraly, Reka [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary); Marian, Terez [Institute of Nuclear Medicine, Debrecen University, Debrecen (Hungary); Pawlak, Dariusz [Institute of Atomic Energy, Radioisotope Centre POLATOM, Swierk-Otwock (Poland); Zaknun, John J.; Pillai, Maroor R.A. [International Atomic Energy Agency (IAEA), Vienna (Austria); Janoki, Gyozo A. [Department of Applied Radioisotopes and Animal Experimentation, National ' Frederic Joliot-Curie' Institute of Radiobiology and Radiohygiene, H-1221 Budapest (Hungary)

    2010-02-15

    Introduction: Radionuclide therapy (RNT) is an effective method for bone pain palliation in patients suffering from bone metastasis. Due to the long half-life, easy production and relatively low {beta}- energy, {sup 177}Lu [T{sub 1/2}=6.73 days, E{sub {beta}}{sub max}=497 keV, E{sub {gamma}}=113 keV (6.4%), 208 keV (11%)]-based radiopharmaceuticals offer logistical advantage for wider use. This paper reports the results of a multispecies biodistribution and toxicity studies of {sup 177}Lu-EDTMP to collect preclinical data for starting human clinical trials. Methods: {sup 177}Lu-EDTMP with radiochemical purity greater than 99% was formulated by using a lyophilized kit of EDTMP (35 mg of EDTMP, 5.72 g of CaO and 14.1 mg of NaOH). Biodistribution studies were conducted in mice and rabbits. Small animal imaging was performed using NanoSPECT/CT (Mediso, Ltd., Hungary) and digital autoradiography. Gamma camera imaging was done in rabbits and dogs. Four levels of activity (9.25 through 37 MBq/kg body weight) of {sup 177}Lu-EDTMP were injected in four groups of three dogs each to study the toxicological effects. Results: {sup 177}Lu-EDTMP accumulated almost exclusively in the skeletal system (peak ca. 41% of the injected activity in bone with terminal elimination half-life of 2130 and 1870 h in mice and rabbits, respectively) with a peak uptake during 1-3 h. Excretion of the radiopharmaceutical was through the urinary system. Imaging studies showed that all species (mouse, rat, rabbit and dog) take up the compound in regions of remodeling bone, while kidney retention is not visible after 1 day postinjection (pi). In dogs, the highest applied activity (37 MBq/kg body weight) led to a moderate decrease in platelet concentration (mean, 160 g/L) at 1 week pi with no toxicity. Conclusion: The protracted effective half-life of {sup 177}Lu-EDTMP in bone supports that modifying the EDTMP molecule by introducing {sup 177}Lu does not alter its biological behaviour as a specific bone

  18. Potential Biomarkers for Radiation-Induced Renal Toxicity following 177Lu-Octreotate Administration in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The kidneys are one of the main dose-limiting organs in peptide receptor radionuclide therapy and due to large inter-individual variations in renal toxicity, biomarkers are urgently needed in order to optimize therapy and reduce renal tissue damage. The aim of this study was to investigate the transcriptional, functional, and morphological effects on renal tissue after 177Lu-octreotate administration in normal mice, and to identify biomarkers for radiation induced renal toxicity.C57BL/6N mice were i.v. injected with 0, 30, 60, 90, 120, or 150 MBq 177Lu-octreotate (0, 16, 29, 40, 48, and 54 Gy to the kidneys. At 4, 8, and 12 months after administration, radiation-induced effects were evaluated in relation to (a global transcriptional variations in kidney tissues, (b morphological changes in the kidneys, (c changes in white and red blood cell count as well as blood levels of urea, and (d changes in renal function using 99mTc-DTPA/99mTc-DMSA scintigraphy.In general, the highest number of differentially regulated transcripts was observed at 12 months after administration. The Cdkn1a, C3, Dbp, Lcn2, and Per2 genes displayed a distinct dose-dependent regulation, with increased expression level with increasing absorbed dose. Ifng, Tnf, and Il1B were identified as primary up-stream regulators of the recurrently regulated transcripts. Furthermore, previously proposed biomarkers for kidney injury and radiation damage were also observed. The functional investigation revealed reduced excretion of 99mTc-DTPA after 150 MBq, an increased uptake of 99mTc-DMSA at all dose levels compared with the controls, and markedly increased urea level in blood after 150 MBq at 12 months.Distinct dose-response relationships were found for several of the regulated transcripts. The Cdkn1a, Dbp, Lcn2, and Per2 genes are proposed as biomarkers for 177Lu-octreotate exposure of kidney. Correlations to functional and morphological effects further confirm applicability of these

  19. Hypocalcaemia after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Vliet, Esther I. van; Kam, Boen L.R.; Teunissen, Jaap J.M.; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus MC, University Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Zillikens, M.C.; Peeters, Robin P. [Erasmus MC, University Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus MC, University Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2013-12-15

    The aim of this study was to explore the possible mechanisms involved in an observed decline in serum calcium levels in patients with a neuroendocrine tumour (NET) treated with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). In 47 patients with NET who were normocalcaemic at baseline, serum calcium, albumin, creatinine, alkaline phosphatase, gamma glutamyl transpeptidase, magnesium, phosphate and 25-hydroxyvitamin D were prospectively analysed at baseline and up to 6 months after treatment. Parathyroid hormone (PTH), 1,25-dihydroxyvitamin D{sub 3}, type 1 aminoterminal propeptide of procollagen, bone-specific alkaline phosphatase, carboxyterminal crosslinking telopeptide of bone collagen, collagen type I crosslinked N-telopeptide, and creatinine and calcium in 24-h urine samples, were evaluated at baseline and at 3 and 6 months. Another 153 patients with NET were included in a retrospective study to estimate the occurrence of hypocalcaemia in a larger patient group. In the prospectively included patients, the mean serum calcium level decreased significantly after treatment (2.31 {+-} 0.01 to 2.26 {+-} 0.02 mmol/l, p = 0.02). Eight patients (17 %) showed a marked decrease in serum calcium levels with a nadir of {<=}2.10 mmol/l. In five patients (11 %), calcium substitution therapy was prescribed. PTH increased significantly (5.9 {+-} 0.6 to 6.7 {+-} 0.8 pmol/l, p = 0.02), presumably in response to the decreasing serum calcium levels. 25-Hydroxyvitamin D remained stable after treatment. Creatinine levels increased significantly (73 {+-} 3 to 77 {+-} 3 {mu}mol/l, p = 0.01), but not enough to explain the hypocalcaemia. Phosphate levels remained unaffected. In the retrospectively analysed patients, the mean serum calcium level decreased significantly from 2.33 {+-} 0.01 at baseline to a nadir of 2.24 {+-} 0.01 mmol/l at 18 months after treatment (p < 0.001). Of the 153 patients, 33 (22 %) showed a serum calcium nadir of {<=}2.10 mmol/l, and 11

  20. Photon strength functions in 177Lu: Study of scissors resonance in high-spin region

    Directory of Open Access Journals (Sweden)

    Bečvář F.

    2015-01-01

    Full Text Available The nucleus 177Lu is characteristic by an unusually high value of the thermal-neutron capturing state spin, J = 13/2, and by distinct low-energy rotational bands built on the 7/2+ ground state and the 9/2− level at 150 keV. The γ cascades connecting the capturing state with the members of these bands carry unique information about the role of identical M1 scissors-mode resonances, built according to Brink hypothesis assumingly on each energy level, even in conditions of fast nuclear rotation. With this motivation we measured a set of spectra of two-step γ cascades following the thermal neutron capture in 176Lu. The measurement was performed at neutron beam of the LWR-15 Reactor in Řež. From the analysis of these spectra the common parameters of the scissors resonances were deduced. The obtained results are discussed.

  1. Effect of amplified spontaneous emission on selectivity of laser photoionisation of the 177Lu radioisotope

    Science.gov (United States)

    D'yachkov, A. B.; Gorkunov, A. A.; Labozin, A. V.; Mironov, S. M.; Panchenko, V. Ya; Firsov, V. A.; Tsvetkov, G. O.

    2016-06-01

    A significant deselecting effect of amplified spontaneous emission has been observed in the experiments on selective laser photoionisation of the 177Lu radioisotope according to the scheme 5d6s2 2D3/2 → 5d6s6p 4Fo5/2 (18505 cm-1) → 5d6s7s 4D3/2(37194 cm-1) → autoionisation state (53375 cm-1). The effect is conditioned by involvement of non-target isotopes from the lower metastable level 5d6s2 2D5/2(1994 cm-1) into the ionisation process. Spectral filtering of spontaneous emission has allowed us to significantly increase the selectivity of the photoionisation process of the radioisotope and to attain a selectivity value of 105 when using saturating light intensities.

  2. Preparation and Biological Evaluation of 188Re Labeled Monoclonal Antibody TGLA

    Institute of Scientific and Technical Information of China (English)

    WEN; Kai; ZHANG; Jun-li; CHEN; Bao-jun; CUI; Hai-ping

    2012-01-01

    <正>Monoclonal antibody TGLA is a specific targeting CD20 chimeric antibody. It can kill tumor cells and inhibit tumor cells’ growth effectively, which has been applied to clinical therapy of lymphoma cell B. 188 Re is easy to get, and emits both β and γ rays. 188Re labeled monoclonal antibody TGLA can be used for the study of lymphoma therapy and imaging. This work got the product 188Re-TGLA by direct labeling

  3. Preparation and bioevaluation of {sup 177}Lu-labelled anti-CD44 for radioimmunotherapy of colon cancer

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-12-15

    CD44 is a particular adhesion molecule and facilitates both cell-cell and cell-matrix interactions. In particular, splice variants of CD44 are particularly overexpressed in a large number of malignancies and carcinomas. In this study, the {sup 177}Lu-labelled CD44 targeting antibody was prepared and bioevaluated in vitro and in vivo. Anti-CD44 was immunoconjugated with the equivalent molar ratio of cysteine-based dtPA-ncS and radioimmunoconjugated with {sup 177}Lu at room temperature within 15 minutes. the stability was tested in human serum. An in vitro study was carried out in Ht-29 human colon cancer cell lines. For the biodistribution study {sup 177}Lu-labelled anti-CD44 was injected in xenograft mice. Anti-CD44 was immunoconjugated with cysteinebased dtPA-ncS and purified by a centricon filter system having a molecular cut-off of 50 kda. radioimmunoconjugation with {sup 177}Lu was reacted for 15 min at room temperature. the radiolabeling yield was >99%, and it was stable in human serum without any fragmentation or degradation. The radioimmunoconjugate showed a high binding affinity on HT-29 colon cancer cell surfaces. In a biodistribution study, the tumor-to-blood ratio of the radioimmunoconjugate was 43 : 1 at 1 day post injection (p.i) in human colon cancer bearing mice. the anti-CD44 monoclonal antibody for the targeting of colon cancer was effectively radioimmunoconjugated with {sup 177}Lu. the in vitro high immunoactivity of this radioimmunoconjugate was determined by a cell binding assay. In addition, the antibody's tumor targeting ability was demonstrated with very high uptake in tumors. this radioimmunoconjugate is applicable to therapy in human colon cancer with highly expressed CD44.

  4. Preparation and primary biological evaluation of novel nitrido-188Re complexes/lipiodol

    Institute of Scientific and Technical Information of China (English)

    WANG Guanquan; WEI Hongyuan; LUO Shunzhong; HE Jiaheng; YANG Yuqing; WANG Wenjin; XIONG Xiaoling

    2008-01-01

    Two new nitrido-188Re complexes were prepared by a modified method in high yield.These complexes were stable in vitro.The biodistribution in normal mice showed that these nitrido-188Re complexes could accumulate in liver and dissipate quickly from almost all organs.TAE was performed with the use of lipiodol solutions of two complexes to rabbit VX2 liver tumor models.SPECT images showed that the two lipiodol solutions could remain in tumor for about 9 h (188ReN-NEPTDD/lipiodol) and 12 h (188ReN-NEMMPTDD/Iipiodol),respectively.

  5. Preparation and bio-distribution of bone tumor therapeutic agent 188Re-TCTMP

    Institute of Scientific and Technical Information of China (English)

    JIANG Shu-Bin; LUO Shun-Zhong; DENG Hou-Fu; BIN Wen-Zeng; WANG Wen-Jin; WEI Hong-Yuan; LIU Guo-Ping

    2004-01-01

    TCTMP ( 1,4,8,11-tetraaza cyclotetradecyl- 1,4,8,11-tetramethylene phosphonate) was synthesized and coupled with 188Re. The 188Re-TCTMP's coupling condition, stability and bio-distribution in mice were investigated.The results showed that satisfactory yield of 188Re could be obtained under the conditions of media pH=2.0, 0.8~1.6 mg of SnCl2 and 50 mg of ligand. 188Re-TCTMP was stable (complexation yield >95%) in 8 d without protection of N2. The result of bio-distribution indicated that 188Re-TCTMP had a strong affinity to skeleton and very low non-target tissue's uptake, and the amount of 188Re-TCTMP in blood was (0.06±0.02)%ID/g 6 h after injection,whereas the concentration of 188Re-HEDP (1-hydroxy-ethylidene diphosphonate) in blood was (0.28±0.05)%ID/g 6 hafter injection. Compared with 188Re-HEDP, 188Re-TCTMP exhibits better potential for the treatment of metastases.

  6. Levels of 188Re nucleus populated in thermal neutron capture reaction

    Science.gov (United States)

    Běrziņš, J.; Krasta, T.; Simonova, L.; Balodis, M.; Bondarenko, V.; Jentschel, M.; Urban, W.; Tomandl, I.

    2016-03-01

    Levels of 188Re populated in thermal neutron capture reaction with enriched 187Re targets have been studied. Single γ-ray spectrum of 188Re, measured with the high-resolution crystal diffraction spectrometer GAMS5, as well as γγ-coincidence experiments performed with high efficiency Ge detectors, allowed to develop model-independent level scheme of the doubly-odd 188Re nucleus up to ˜ 1.5 MeV excitation energy. Analysis of the established 188Re level scheme in terms of the quasiparticle-plus-rotor model indicates coexistence of axially-deformed and triaxial structures in the energy range above 400 keV.

  7. Exploitation of nano alumina for the chromatographic separation of clinical grade 188Re from 188W: a renaissance of the 188W/188Re generator technology.

    Science.gov (United States)

    Chakravarty, Rubel; Shukla, Rakesh; Ram, Ramu; Venkatesh, Meera; Tyagi, Avesh Kumar; Dash, Ashutosh

    2011-08-15

    The (188)W/(188)Re generator using an acidic alumina column for chromatographic separation of (188)Re has remained the most popular procedure world over. The capacity of bulk alumina for taking up tungstate ions is limited (∼50 mg W/g) necessitating the use of very high specific activity (188)W (185-370 GBq/g), which can be produced only in very few high flux reactors available in the world. In this context, the use of high-capacity sorbents would not only mitigate the requirement of high specific activity (188)W but also facilitate easy access to (188)Re. A solid state mechanochemical approach to synthesize nanocrystalline γ-Al(2)O(3) possessing very high W-sorption capacity (500 mg W/g) was developed. The structural and other investigations of the material were carried out using X-ray diffraction (XRD), transmission electron microscopy (TEM), Brunauer Emmett Teller (BET) surface area analysis, thermogravimetric-differential thermal analysis (TG-DTA), and dynamic light scattering (DLS) techniques. The synthesized material had an average crystallite size of ∼5 nm and surface area of 252 ± 10 m(2)/g. Sorption characteristics such as distribution ratios (K(d)), capacity, breakthrough profile, and elution behavior were investigated to ensure quantitative uptake of (188)W and selective elution of (188)Re. A 11.1 GBq (300 mCi) (188)W/(188)Re generator was developed using nanocrystalline γ-Al(2)O(3), and its performance was evaluated for a period of 6 months. The overall yield of (188)Re was >80%, with >99.999% radionuclidic purity and >99% radiochemical purity. The eluted (188)Re possessed appreciably high radioactive concentration and was compatible for the preparation of (188)Re labeled radiopharmaceuticals.

  8. Tumoral fibrosis effect on the radiation absorbed dose of {sup 177}Lu-Tyr{sup 3}-octreotate-gold nanoparticles and {sup 177}Lu-Tyr{sup 3}-octreotate radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Zambrano R, O. D.

    2015-07-01

    In this work was comparatively evaluated the effect of tumoral fibrosis in the radiation absorbed dose of the radiopharmaceutical {sup 177}Lu-Tyr{sup 3}-octreotate with and without gold nanoparticles. For this, was used an experimental array of tumoral fibrosis and computer models based on Monte Carlo calculations to simulate tumoral micro environments without fibrosis and with fibrosis. The computer simulation code Penelope (Penetration Energy Loss of Positron and Electrons) and MCNP (Monte Carlo N-particle Transport Code System) which are based on the Monte Carlo methodology were used to create the computer models for the simulation of the transport of particles (emitted by {sup 177}Lu) in the micro environments (without fibrosis and with fibrosis) with the purpose of calculating the radiation absorbed dose in the interstitial space and in the nucleus of cancer cells. The first computational model consisted of multiple concentric spheres (as onion shells) with the radioactive source homogeneously distributed in the shell between 5 and 10 μm in diameter which represents the internalization of the radioactive source into the cell cytoplasm as it occurs in target specific radiotherapy. The concentric spheres were useful to calculate the radiation absorbed dose in depth in the models without fibrosis and with fibrosis. Furthermore, there were constructed other computer models using two different codes that simulate the transport of radiation (Penelope and MCNP). These models consist of seven spheres that represent cancer cells (HeLa cells) of 10 μm in diameter and each one of them contain another smaller sphere in the center that represents the cell nucleus. A comparison was done of the radiation absorbed dose in the nucleus of the cells, calculated with both codes, Penelope and MCNP. The radioactive source ({sup 177}Lu) used for the simulations was given to the codes by means of a convoluted spectrum of the most important beta particles (high percentage emission

  9. Formulation of an inhibitor radiopharmaceutical of prostatic antigen of {sup 177}Lu-Glu-Nh-CO-Nh-Lys membrane; Formulacion de un radiofarmaco inhibidor del antigeno prostatico de membrana {sup 177}Lu-Glu-NH-CO-NH-Lys

    Energy Technology Data Exchange (ETDEWEB)

    Ortega S, D.

    2015-07-01

    The prostate specific membrane antigen (PSMA) is a zinc metalloenzyme that is expressed on the cell membrane and highly expressed in prostate cancer. Recently, it has been demonstrated that the peptide sequence Glu-Nh-CO-Nh-Lys inhibit PSMA activity through an electrostatic interaction with the Zn. Several theragnostic radiopharmaceuticals with base in {sup 177}Lu have been developed for radiotherapy of specific molecular targets because gamma and beta emissions of the radionuclide (β = 0.498 MeV and γ= 0.133 MeV). However, there is currently no label a formulation for preparing a radiopharmaceutical of {sup 177}Lu-Glu-Nh-CO-Nh-Lys useful treatment of prostate cancer. The aim of this research was to optimize and document the process of production of the radiopharmaceutical {sup 177}Lu-Glu-Nh-CO-Nh-Lys for sanitary registration application before the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). The optimization of the production process was assessed a factorial design of three variables with mixed levels (3 x 3 x 2) where the dependent variable is the radiochemical purity, the analytical method was validated by UV-Vis spectrophotometry. Next, process validation was carried out by labeling 3 lots of the optimized formulation of the radiopharmaceutical (5.55 GBq (2.16 μg) of {sup 177}LuCl{sub 3}, 90 mg peptide PSMA, 50 mg ascorbic acid and 150 μL of acetate buffer 1 M ph 5), long-term stability was performed by high resolution liquid chromatography) to determine its useful shelf life. 3 validation batches were prepared under protocols of Good Manufacturing Practice (GMP) in the Production Plant of Radiopharmaceuticals of the Instituto Nacional de Investigaciones Nucleares (ININ), meet specifications preset by obtaining a sterile and free development of bacterial endotoxin yields of labeled 100% and which retains its quality characteristics radiochemical purity greater than 90% for at least 15 days. (Author)

  10. 177Lu-DTPA-BIS-BIOTIN的制备及正常鼠体内生物分布%Preparation of 177Lu-DTPA-BIS-BIOTIN and Biodistribution Evaluation in Normal Mice

    Institute of Scientific and Technical Information of China (English)

    邓新荣; 杜进; 罗志福

    2010-01-01

    研究了DTPA-BIS-BIOTIN的177Lu标记方法,优化了标记条件,并进行了标记物在正常小鼠体内分布实验.在最佳标记条件下(DTPA-BIS-BIOTIN 25 μg,标记介质pH=4.5,80℃反应20 min),177Lu-DTPA-BIS-BIOTIN标记率大于99.0%,室温下放置96 h,标记物体外稳定性良好.正常小鼠体内分布实验结果表明,177Lu-DTPA-BIS-BIOTIN在血液中清除快,主要浓集于肝、脾和肾,经肾脏排泄.本研究为进一步采用177Lu-DTPA-BIS-BIOTIN进行肿瘤预定位显像及治疗研究提供了实验基础.

  11. 177Lu-Dendrimer Conjugated to Folate and Bombesin with Gold Nanoparticles in the Dendritic Cavity: A Potential Theranostic Radiopharmaceutical

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

    Full Text Available 177Lu-labeled nanoparticles conjugated to biomolecules have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this research was to synthesize 177Lu-dendrimer(PAMAM-G4-folate-bombesin with gold nanoparticles (AuNPs in the dendritic cavity and to evaluate the radiopharmaceutical potential for targeted radiotherapy and the simultaneous detection of folate receptors (FRs and gastrin-releasing peptide receptors (GRPRs overexpressed in breast cancer cells. p-SCN-Benzyl-DOTA was conjugated in aqueous-basic medium to the dendrimer. The carboxylate groups of Lys1Lys3(DOTA-bombesin and folic acid were activated with HATU and also conjugated to the dendrimer. The conjugate was mixed with 1% HAuCl4 followed by the addition of NaBH4 and purified by ultrafiltration. Elemental analysis (EDS, particle size distribution (DLS, TEM analysis, UV-Vis, and infrared and fluorescence spectroscopies were performed. The conjugate was radiolabeled using 177LuCl3 or 68GaCl3 and analyzed by radio-HPLC. Studies confirmed the dendrimer functionalization with high radiochemical purity (>95%. Fluorescence results demonstrated that the presence of AuNPs in the dendritic cavity confers useful photophysical properties to the radiopharmaceutical for optical imaging. Preliminary binding studies in T47D breast cancer cells showed a specific cell uptake (41.15±2.72%. 177Lu-dendrimer(AuNP-folate-bombesin may be useful as an optical and nuclear imaging agent for breast tumors overexpressing GRPR and FRs, as well as for targeted radiotherapy.

  12. Distinct microRNA expression profiles in mouse renal cortical tissue after 177Lu-octreotate administration.

    Directory of Open Access Journals (Sweden)

    Emil Schüler

    Full Text Available The aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers.Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples.In total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively. No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways.In conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration.

  13. Therapeutic Efficacy with Treatment-related Toxicities of {sup 177}Lu-labeled Bombesin Derivative for the Peptide Receptor Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Cheong; Cho, Eun Ha; Lee, So Young [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-05-15

    The gastrin-releasing peptide receptor (GRPR) has been shown to be overexpressed in many human tumours, including breast cancer, prostate cancer, small cell lung cancer, ovarian cancers, endometrial cancers, and gastrointestinal stromal tumors. In particular, GRPR expression is high in 83 % of invasive primary prostatic carcinomas. These results suggest that {sup 177}Lu-labeled bombesin derivative has promising characteristics as a novel nuclear medicine, especially for the treatment of GRPR over-expressing prostate tumors.

  14. Long-term toxicity of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Bijster, Magda; Jong, Marion de [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Visser, Theo J. [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC Rotterdam, Department of Pathology, Rotterdam (Netherlands); Lindemans, Jan [Erasmus MC Rotterdam, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2007-02-15

    Studies on peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues have shown promising results with regard to tumour control. The efficacy of PRRT is limited by uptake and retention in the proximal tubules of the kidney, which might lead to radiation nephropathy. We investigated the long-term renal toxicity after different doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate and the effects of dose fractionation and lysine co-injection in two tumour-bearing rat models. Significant renal toxicity was detected beyond 100 days after start of treatment as shown by elevated serum creatinine and proteinuria. Microscopically, tubules were strongly dilated with flat epithelium, containing protein cylinders. Creatinine levels rose significantly after 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, but were significantly lower after 278 MBq (single injection) or two weekly doses of 278 MBq. Renal damage scores were maximal after 555 MBq and significantly lower in the 278 and 2 x 278 MBq groups. Three doses of 185 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469{+-}18, 134{+-}70 and 65{+-}15 {mu}mol/l, respectively; p<0.001). Renal histological damage scores were not significantly influenced by dose fractionation. Lysine co-administration with three weekly treatments of 185 MBq significantly lowered serum creatinine and proteinuria. Injection of high doses of [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. (orig.)

  15. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M. [Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga No. 15, 14000 Mexico D.F. (Mexico); Ferro F, G. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, 06000 Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses after administration of {sup 177}Lu-DOTA-TATE in mice as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (n=18) to obtain the {sup 177}Lu-DOTA-TATE biokinetics and dosimetry. To estimate its therapeutic efficacy 87 MBq were injected in a tail vein of 3 mice and 19 days p.i. there were a partial relapse. There was an epithelial and sarcoma mixed tumour in the kidneys of mouse III. The absorbed dose to tumour, kidney and pancreas was 50.5 {+-} 7.2 Gy, 17.5 {+-} 2.5 Gy and 12.6 {+-} 2.3 Gy respectively. These studies justify further therapeutic and dosimetry estimations to ensure that {sup 177}Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

  16. {sup 177}Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to {sup 213}Bi-immunotherapy, but causes toxicity not observed with {sup 213}Bi

    Energy Technology Data Exchange (ETDEWEB)

    Seidl, Christof; Zoeckler, Christine; Beck, Roswitha; Senekowitsch-Schmidtke, Reingard [Technische Universitaet Muenchen, Department of Nuclear Medicine, Munich (Germany); Quintanilla-Martinez, Leticia [Universitaetsklinikum Tuebingen, Institute for Pathology, Tuebingen (Germany); Bruchertseifer, Frank [Institute for Transuranium Elements, European Commission, Joint Research Centre, Karlsruhe (Germany)

    2011-02-15

    {sup 213}Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the {beta}-emitter {sup 177}Lu has proven to be beneficial in targeted therapy, {sup 177}Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of {sup 213}Bi-d9MAb. Nude mice were inoculated intraperitoneally with HSC45-M2 gastric cancer cells expressing d9-E-cadherin and were treated intraperitoneally 1 or 8 days later with different activities of specific {sup 177}Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific {sup 177}Lu-d8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of {sup 177}Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Treatment with {sup 177}Lu-immunoconjugates (1.85, 7.4, 14.8 MBq) significantly prolonged survival. As expected, treatment on day 1 after tumour cell inoculation was more effective than treatment on day 8, and specific {sup 177}Lu-d9MAb conjugates were superior to nonspecific {sup 177}Lu-d8MAb. Treatment with 7.4 MBq of {sup 177}Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of {sup 177}Lu-d9MAb was not free of toxic side effects. In some animals lymphoblastic lymphoma, proliferative glomerulonephritis and hepatocarcinoma were seen but were not observed after treatment with {sup 213}Bi-d9MAb at comparable therapeutic efficacy. The therapeutic efficacy of {sup 177}Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with {sup 213}Bi-d9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis. (orig.)

  17. {sup 177}Lu-DOTATATE therapy in patients with neuroendocrine tumours: 5 years' experience from a tertiary cancer care centre in India

    Energy Technology Data Exchange (ETDEWEB)

    Danthala, Madhav; Raghavendra Rao, M. [HCG Oncology Hospitals, Bangalore, Karnataka (India); Kallur, K.G.; Prashant, G.R.; Rajkumar, K. [HCG Oncology Hospitals, Department of Nuclear Medicine, Bangalore, Karnataka (India)

    2014-07-15

    The choice of an appropriate treatment option in patients with inoperable or metastatic neuroendocrine tumours (NETs) is limited, and approximately 50 % of patients have advanced NET at diagnosis, and 65 % die within 5 years. Treatment with {sup 177}Lu-DOTATATE ({sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}] octreotate) is a promising new option in the treatment of metastatic NETs. Patients with metastatic NET who underwent {sup 177}Lu-DOTATATE during the period 2009 to 2013 were included in this retrospective study. Follow-up imaging studies including a {sup 68}Ga-DOTANOC PET/CT scan and a posttherapy {sup 177}Lu-DOTATATE scan were compared with baseline imaging to determine response to treatment. Progression-free survival (PFS) was calculated using the Kaplan-Meier method and Cox regression analysis was also done. Ten patients (25 %) had a minimal response, 13 (32.5 %) had a partial response and 9 (22.5 %) had stable disease. Progressive disease was seen in 8 patients (20 %), including 6 patients who died during or after the treatment period. The estimated mean PFS in those who received one or two cycles of {sup 177}Lu-DOTATATE was 8.3 months (95 % CI 6.2 to 10.3 months) compared to an estimated mean PFS of 45.6 months (95 % CI 40.9 to 50.2 months) in those who received more than two cycles of {sup 177}Lu-DOTATATE (log-rank Mantel-Cox Χ {sup 2} = 8.01, p = 0.005). Our study showed that treatment with {sup 177}Lu-DOTATATE should be considered in the management of NETs, considering the limited success of alternative treatment modalities. Treatment response and PFS is determined primarily by the dose delivered and best results are obtained when more than two cycles of {sup 177}Lu-DOTATATE are given, with careful monitoring for possible side effects. (orig.)

  18. Somatostatin-based radiopeptide therapy with [{sup 177}Lu-DOTA]-TOC versus [{sup 90}Y-DOTA]-TOC in neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Marincek, N.; Walter, M.A. [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Koller, M.T. [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); Maecke, H.R. [University Hospital Basel, Division of Radiochemistry, Basel (Switzerland); Rochlitz, C. [University Hospital Basel, Department of Oncology, Basel (Switzerland); Briel, M. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland); McMaster University, Department of Clinical Epidemiology and Biostatistics, Hamilton (Canada); Schindler, C. [University of Basel, Swiss Tropical and Public Health Institute, Basel (Switzerland)

    2014-02-15

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides {sup 90}Y or {sup 177}Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. In a comparative cohort study, patients with advanced neuroendocrine tumours underwent repeated cycles of [{sup 90}Y-DOTA]-TOC or [{sup 177}Lu-DOTA]-TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were employed to examine predictors of survival and adverse events for both treatment groups. Overall, 910 patients underwent 1,804 cycles of [{sup 90}Y-DOTA]-TOC and 141 patients underwent 259 cycles of [{sup 177}Lu-DOTA]-TOC. The median survival after [{sup 177}Lu-DOTA]-TOC and after [{sup 90}Y-DOTA]-TOC was comparable (45.5 months versus 35.9 months, hazard ratio 0.91, 95 % confidence interval 0.63-1.30, p = 0.49). Subgroup analyses revealed a significantly longer survival for [{sup 177}Lu-DOTA]-TOC over [{sup 90}Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [{sup 177}Lu-DOTA]-TOC treatment (1.4 vs 10.1 %, p = 0.001), while the rate of severe permanent renal toxicities was similar in both treatment groups (9.2 vs 7.8 %, p = 0.32). The present results revealed no difference in median overall survival after [{sup 177}Lu-DOTA]-TOC and [{sup 90}Y-DOTA]-TOC. Furthermore, [{sup 177}Lu-DOTA]-TOC was less haematotoxic than [{sup 90}Y-DOTA]-TOC. (orig.)

  19. Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs in vivo

    Directory of Open Access Journals (Sweden)

    Tang QS

    2011-11-01

    Full Text Available Qiu-Sha Tang1,*, Dao-Zhen Chen2,*, Wen-Qun Xue2, Jing-Ying Xiang2, Yong-Chi Gong1, Li Zhang2, Cai-Qin Guo21Department of Pathology and Pathophysiology, Medical College, Southeast University, Nanjing, Jiangsu; 2Central Laboratory, Wuxi Hospital for Maternal and Child Health Care, Affiliated Medical School of Nanjin, Wuxi, Jiangsu, China *Authors contributed equally to this workBackground: The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide 188Re-labeled folic acid ligand (188Re-folate-CDDP/HSA.Methods: Human serum albumin was labeled with 188Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g was measured in vital organs. The biodistribution of 188Re-folate-CDDP/HAS magnetic nanoparticles was assessed.Results: Optimal conditions for 188Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L, 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL, 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L, 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and 188ReO4 eluent (0.1 mL. The rate of 188Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the 188Re-folate-CDDP/HSA magnetic nanoparticles

  20. Rhenium-188: Availability from the W-188/Re-188 Generator and Status of Current Applications

    Energy Technology Data Exchange (ETDEWEB)

    Pillai, M R A [Bhabha Atomic Research Centre, Mumbai, India; Dash, A [Bhabha Atomic Research Centre, Mumbai, India; Knapp Jr, Russ F [ORNL

    2012-01-01

    Rhenium-188 is one of the most readily available generator derived and useful radionuclides for therapy emitting - particles (2.12 MeV, 71.1% and 1.965 MeV, 25.6%) and imageable gammas (155 KeV, 15.1%). The 188W/188Re generator is an ideal source for the long term (4-6 months) continuous availability of no carrier added (nca) 188Re suitable for the preparation of radiopharmaceuticals for radionuclide therapy. The challenges associated with the double neutron capture route of production of the parent 188W radionuclide have been a major impediment in the progress of application of 188Re. Tungsten-188 of adequate specific activity can be prepared only in 2-3 of the high flux reactors operating in the World. Several useful technologies have been developed for the preparation of clinical grade 188W/188Re generator. Since the specific activity of 188W used in the generator is relatively low (<5 Ci/g), the eluted 188ReO4- can have low radioactive concentration often insufficient for radiopharmaceutical preparation. However, several efficient post elution concentration techniques have been developed that yield clinically useful 188ReO4-. Rhenium-188 has been used for the preparation of therapeutic radiopharmaceuticals for the management of diseases such as bone metastasis, rheumatoid arthritis and primary cancers. Several early phase clinical studies using radiopharmaceuticals based on 188Re-labeled phosphonates, antibodies, peptides, lipiodol and particulates have been reported. This article reviews the availability, and use of188Re including a discussion of why broader use of 188Re has not progressed as ecpected as a popular radionuclide for therapy.

  1. The challenges of treating paraganglioma patients with {sup 177}Lu-DOTATATE PRRT: Catecholamine crises, tumor lysis syndrome and the need for modification of treatment protocols

    Energy Technology Data Exchange (ETDEWEB)

    Makis, William; Mccann, Karey; Mcewan, Alexander J. B. [Dept. of Diagnostic Imaging, Cross Cancer Institute, Alberta (China)

    2015-09-15

    A high percentage of paragangliomas express somatostatin receptors that can be utilized for targeted radioisotope therapy. The aim of this study was to describe and discuss the challenges of treating these tumors with {sup 177}Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of {sup 177}Lu-DOTATATE and were evaluated for side effects and response to therapy. Two of the three patients developed severe adverse reactions following their first {sup 177}Lu-DOTATATE treatment. One patient developed a catecholamine crisis and tumor lysis syndrome within hours of treatment, requiring intensive care unit (ICU) support, and another developed a catecholamine crisis 3 days after treatment, requiring hospitalization. The treatment protocols at our institution were subsequently modified by increasing the radioisotope infusion time from 15 to 30 min, as recommended in the literature, to 2–4 h and by reducing the administered dose of {sup 177}Lu-DOTATATE. Subsequent {sup 177}Lu-DOTATATE treatments utilizing the modified protocols were well tolerated, and response to therapy was achieved in all three patients, resulting in significantly improved quality of life. {sup 177}Lu-DOTATATE is an exciting new therapeutic option in the management of paragangliomas; however, current treatment protocols described in the literature may need to be modified by lengthening the infusion time and/or lowering the initial treatment dose to prevent or reduce the severity of adverse reactions.

  2. Dosimetry for {sup 177}Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Delker, Andreas; Fendler, Wolfgang Peter; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Bartenstein, Peter; Boening, Guido [Ludwig-Maximilians-University of Munich, Department of Nuclear Medicine, Munich (Germany); Kratochwil, Clemens; Haberkorn, Uwe [Heidelberg University Hospital, Department for Nuclear Medicine, Heidelberg (Germany); Tritschler, Stefan; Stief, Christian Georg [Ludwig-Maximilians-University of Munich, Department of Urology, Munich (Germany); Kopka, Klaus [German Cancer Research Center (dkfz), Division of Radiopharmaceutical Chemistry, Heidelberg (Germany)

    2016-01-15

    Dosimetry is critical to achieve the optimal therapeutic effect of radioligand therapy (RLT) with limited side effects. Our aim was to perform image-based absorbed dose calculation for the new PSMA ligand {sup 177}Lu-DKFZ-PSMA-617 in support of its use for the treatment of metastatic prostate cancer. Whole-body planar images and SPECT/CT images of the abdomen were acquired in five patients (mean age 68 years) for during two treatment cycles at approximately 1, 24, 48 and 72 h after administration of 3.6 GBq (range 3.4 to 3.9 GBq) {sup 177}Lu-DKFZ-PSMA-617. Quantitative 3D SPECT OSEM reconstruction was performed with corrections for photon scatter, photon attenuation and detector blurring. A camera-specific calibration factor derived from phantom measurements was used for quantitation. Absorbed doses were calculated for various organs from the images using a combination of linear approximation, exponential fit, and target-specific S values, in accordance with the MIRD scheme. Absorbed doses to bone marrow were estimated from planar and SPECT images and with consideration of the blood sampling method according to the EANM guidelines. The average (± SD) absorbed doses per cycle were 2.2 ± 0.6 Gy for the kidneys (0.6 Gy/GBq), 5.1 ± 1.8 Gy for the salivary glands (1.4 Gy/GBq), 0.4 ± 0.2 Gy for the liver (0.1 Gy/GBq), 0.4 ± 0.1 Gy for the spleen (0.1 Gy/GBq), and 44 ± 19 mGy for the bone marrow (0.012 Gy/GBq). The organ absorbed doses did not differ significantly between cycles. The critical absorbed dose reported for the kidneys (23 Gy) was not reached in any patient. At 24 h there was increased uptake in the colon with 50 - 70 % overlap to the kidneys on planar images. Absorbed doses for tumour lesions ranged between 1.2 and 47.5 Gy (13.1 Gy/GBq) per cycle. The salivary glands and kidneys showed high, but not critical, absorbed doses after RLT with {sup 177}Lu-DKFZ-PSMA-617. We suggest that {sup 177}Lu-DKFZ-PSMA-617 is suitable for radiotherapy, offering tumour

  3. Nanocrystalline zirconia: a novel sorbent for the preparation of (188)W/(188)Re generator.

    Science.gov (United States)

    Chakravarty, Rubel; Shukla, Rakesh; Tyagi, A K; Dash, Ashutosh; Venkatesh, Meera

    2010-02-01

    Nanocrystalline zirconia, a novel high capacity sorbent material was synthesized and tested for its utility in the preparation of (188)W/(188)Re generators. The structural investigation of the material was carried out using X-ray diffraction, surface area determination, FTIR and TEM micrograph analysis. Various experimental parameters were optimized to separate (188)Re from (188)W. The capacity of the material was found to be approximately 325mgW/g at the optimum pH. A chromatographic (188)W/(188)Re generator was developed using this material from which >80% of (188)Re generated could be eluted with 0.9% saline solution, with high radionuclidic, radiochemical and chemical purity and appreciably high radioactive concentration suitable for radiopharmaceutical applications.

  4. Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} and {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α; Evaluacion de la eficacia terapeutica y radiotoxicidad de los conjugados {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} y {sup 177}Lu-DOTA-GGC-AuNP-c[RGDfK(C)] en un modelo murino y su relacion con la inhibicion de los factores angiogenicos VEGF y HIF-1α

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2013-07-01

    Molecular targeting therapy has become a relevant therapeutic strategy for cancer. The principle that peptide receptors can be used successfully for in vivo targeting of human cancers has been proven, and radiolabeled peptides have been demonstrated to be effective in patients with malignant tumors. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been designed to antagonize the function of α(v)β(3) integrin, thereby inhibiting angio genesis. The conjugation of RGD peptides to radiolabeled gold nanoparticles (AuNP) produces biocompatible and stable m ultimeric systems with target-specific molecular recognition. The aim of this research was to evaluate the therapeutic response of {sup 177}Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of {sup 177}Lu-AuNP or {sup 177}Lu-RGD. The radiation absorbed dose, metabolic activity (SUV, [18F]fluor-deoxy-glucose-micro PET/CT), renal radiotoxicity, renal and tumoral histological characteristics as well as tumoral VEGF and HIF-1? gene expression (by realtime polymerase chain reaction) following treatment with {sup 177}Lu-AuNP-RGD, {sup 177}Lu-AuNP or {sup 177}Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, {sup 177}Lu-AuNP-RGD delivered the highest tumor radiation absorbed dose (63.8 ± 7.9 Gy) vs other treatments. These results correlated with the observed therapeutic response, in which {sup 177}Lu-AuNP-RGD significantly (p<0.05) reduced tumor progression, tumor metabolic activity, intratumoral vessels and VEGF gene expression compared to the other radiopharmaceuticals. This was consequence of high tumor retention and a combination of molecular targeting therapy (m ultimeric RGD system) and radiotherapy ({sup 177}Lu). There was a low uptake in non-target organs and no induction of renal toxicity. {sup 177}Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

  5. External beam radiotherapy synergizes 188Re-liposome against human esophageal cancer xenograft and modulates 188Re-liposome pharmacokinetics

    Directory of Open Access Journals (Sweden)

    Chang CH

    2015-05-01

    Full Text Available Chih-Hsien Chang,1,2 Shin-Yi Liu,3 Chih-Wen Chi,3 Hsiang-Lin Yu,1 Tsui-Jung Chang,1 Tung-Hu Tsai,4 Te-Wei Lee,1 Yu-Jen Chen3–5 1Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan; 2Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, 3Department of Medical Research MacKay Memorial Hospital, 4Institute of Traditional Medicine, National Yang-Ming University, 5Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan Abstract: External beam radiotherapy (EBRT treats gross tumors and local microscopic diseases. Radionuclide therapy by radioisotopes can eradicate tumors systemically. Rhenium 188 (188Re-liposome, a nanoparticle undergoing clinical trials, emits gamma rays for imaging validation and beta rays for therapy, with biodistribution profiles preferential to tumors. We designed a combinatory treatment and examined its effects on human esophageal cancer xenografts, a malignancy with potential treatment resistance and poor prognosis. Human esophageal cancer cell lines BE-3 (adenocarcinoma and CE81T/VGH (squamous cell carcinoma were implanted and compared. The radiochemical purity of 188Re-liposome exceeded 95%. Molecular imaging by NanoSPECT/CT showed that BE-3, but not CE81T/VGH, xenografts could uptake the 188Re-liposome. The combination of EBRT and 188Re-liposome inhibited tumor regrowth greater than each treatment alone, as the tumor growth inhibition rate was 30% with EBRT, 25% with 188Re-liposome, and 53% with the combination treatment at 21 days postinjection. Combinatory treatment had no additive adverse effects and significant biological toxicities on white blood cell counts, body weight, or liver and renal functions. EBRT significantly enhanced the excretion of 188Re-liposome into feces and urine. In conclusion, the combination of EBRT with 188Re-liposome might be a potential treatment modality for esophageal cancer. Keywords: Radionuclide

  6. Comparative studies of antibody anti-CD20 labeled with {sup 188}Re; Estudo comparativo da marcacao do anticorpo anti-CD20 com {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta de Barros Rodrigues

    2010-07-01

    Nuclear Medicine is an unique and important modality in oncology and the development of new tumor-targeted radiopharmaceuticals for both diagnosis and therapy is an area of interest for researchers. Rituximab (RTX) is a quimeric monoclonal antibody (mAb) (IgG 1) that specifically binds to CD20 antigen with high affinity and has been successfully used for the treatment of Non-Hodgkin Lymphoma (NHL) of cell B. The CD20 antigen is expressed over more than 90% of cell B NHL. Technetium-99m ({sup 99m}Tc) and rhenium-188 ({sup 188}Re) are an attractive radionuclide pair for clinical use due to their favorable decay properties for diagnosis ({sup 99m}Tc: T{sub 1/2} = 6 h, {gamma} radiation = 140 keV) and therapy ({sup 188}Re: T{sub 1/2} = 17 h, maximum {beta} energy = 2.12 MeV) and to their availability in the form of {sup 99}Mo/{sup 99}mTc and {sup 188}W/{sup 188}Re generators. The radionuclides can be conjugated to mAb using similar chemical procedures. The aim of this work was to study the labeling of anti-CD20 mAb (RTX) with {sup 188}Re using two techniques: the direct labeling method [{sup 188}Re(V)] and the labeling method via the carbonyl nucleus [{sup 188}Re(I)]. Besides the quality control, the radiolabeled mAb was submitted to in vivo, in vitro and ex vivo biological studies. For the direct labeling, RTX was reducing by incubation with 2-mercaptoethanol for generating sulphydryl groups (-SH) and further labeled with {sup 188}Re(V), in a study of several parameters in order to reach an optimized formulation. The labeling via the carbonyl nucleus both {sup 99}mTc and {sup 188}Re were employed through 2 different procedures: (1) labeling of intact RTX with {sup 99}mTc(I) and (2) reduced RTX (RTX{sub red}) labeled with {sup 99}mTc(I)/{sup 188}Re(I). Also a parameter study was performed to obtain an optimized formulation. The quality control method for evaluating the radiochemical purity showed a good labeling yield (93%) for the direct method. The labeling method

  7. In vivo quantification of {sup 177}Lu with planar whole-body and SPECT/CT gamma camera imaging

    Energy Technology Data Exchange (ETDEWEB)

    Bailey, Dale L. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Faculty of Health Sciences, University of Sydney, Cumberland, NSW (Australia); Sydney Medical School, University of Sydney, Camperdown, NSW (Australia); NETwork, Sydney Vital, St Leonards, Sydney, NSW (Australia); Hennessy, Thomas M.; Willowson, Kathy P.; Henry, E. Courtney [Institute of Medical Physics, University of Sydney, Camperdown, NSW (Australia); Chan, David L.H. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); NETwork, Sydney Vital, St Leonards, Sydney, NSW (Australia); Aslani, Alireza [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Roach, Paul J. [Department of Nuclear Medicine, Royal North Shore Hospital, St Leonards, NSW 2065 (Australia); Sydney Medical School, University of Sydney, Camperdown, NSW (Australia)

    2015-09-17

    Advances in gamma camera technology and the emergence of a number of new theranostic radiopharmaceutical pairings have re-awakened interest in in vivo quantification with single-photon-emitting radionuclides. We have implemented and validated methodology to provide quantitative imaging of {sup 177}Lu for 2D whole-body planar studies and for 3D tomographic imaging with single-photon emission computed tomography (SPECT)/CT. Whole-body planar scans were performed on subjects to whom a known amount of [{sup 177}Lu]-DOTA-octreotate had been administered for therapy. The total radioactivity estimated from the images was compared with the known amount of the radionuclide therapy administered. In separate studies, venous blood samples were withdrawn from subjects after administration of [{sup 177}Lu]-DOTA-octreotate while a SPECT acquisition was in progress and the concentration of the radionuclide in the venous blood sample compared with that estimated from large blood pool structures in the SPECT reconstruction. The total radioactivity contained within an internal SPECT calibration standard was also assessed. In the whole-body planar scans (n = 28), the estimated total body radioactivity was accurate to within +4.6 ± 5.9 % (range −17.1 to +11.2 %) of the correct value. In the SPECT reconstructions (n = 12), the radioactivity concentration in the cardiac blood pool was accurate to within −4.0 ± 7.8 % (range −16.1 to +7.5 %) of the true value and the internal standard measurements (n = 89) were within 2.0 ± 8.5 % (range −16.3 to +24.2 %) of the known amount of radioactivity contained. In our hands, state-of-the-art hybrid SPECT/CT gamma cameras were able to provide accurate estimates of in vivo radioactivity to better than, on average, ±10 % for use in biodistribution and radionuclide dosimetry calculations.

  8. Application of analytic methodologies for image quantification in neuroendocrine tumor therapy with {sup 177}Lu-DOTA

    Energy Technology Data Exchange (ETDEWEB)

    Kubo, T.T.A.; Oliveira, S.M.V. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Marco, L.; Mamede, M., E-mail: tadeukubo@gmail.com [Instituto Nacional do Cancer, Rio de Janeiro, RJ (Brazil)

    2012-07-01

    Neuroendocrine tumors have annual incidence of 1 to 2 cases per one hundred thousand inhabitants. The {sup 177}Lu-DOTA-octreotate treatments in 3 or 4 cycles has been effective in controlling disease progression and, in some cases, promote tumor remission. To estimate radiation side effects in healthy organs, image quantification techniques have been broadcast for individualized patient dosimetry. In this paper, image data processing methods are presented to allowing comparisons between different image conjugate views, combined with attenuation correction and system sensitivity. Images were acquired 24, 72 and 192 h after administration of 74 GBq of {sup 177}Lu-DOTA using a dual-head gamma camera detection system and they were evaluated with ImageJ software. 4 female patients underwent to two cycles of treatment. The kidneys, liver and whole-body regions of interest were separately assessed by 4 techniques for counts method and 12 techniques for pixel intensity method, considering the main photopeak separately and aided by the attenuation correction map and adjacent windows to photopeak energy. The pixel intensity method was combined with mathematical correction for pixels with null value. The results obtained by the two methods were strongly correlated (r>0.9) (p<0.001). The paired t-test accepted the null hypothesis of compatibility between the two methods (with and without attenuation correction map) (p<0.05), but rejected it when the adjacent windows were combined. No significant tumor reduction (p>0.05) was found between the treatment cycles. In conclusion, the pixel intensity method is faster and allows macros, minimizing operator error, and may optimize dosimetry in tumor therapies with {sup 177}Lu-DOTA-octreotate. (author)

  9. 188Re-LABELED HYPERBRANCHED POLYSULFONAMINE AS A ROBUST TOOL FOR TARGETED CANCER DIAGNOSIS AND RADIOIMMUNOTHERAPY

    Institute of Scientific and Technical Information of China (English)

    Nan Li; Yue Jin; Li-zhe Xue; Pei-yong Li; De-yue Yan; Xin-yuan Zhu

    2013-01-01

    Hyperbranched polysulfonamine (HPSA) is a promising biomaterial due to its highly branched spherical architecture and efficient intracellular translocation.To realize the functionalization of HPSA,both N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP) for tethering the human-mouse chimeric monoclonal antibody CH12 and N-hydroxy succinimidyl S-acetylmercaptoacetyltriglycinate (NHS-MAG3) for labeling 188Re were sequentially grafted onto the primary amine terminals of HPSA via covalent linkages,attaining the SPDP-HPSA-MAG3 intermediate.In order to reserve the structural integrity of CH12,the fragment crystallizable (Fc) region was also processed by oxidation of oligosaccharide moieties with sodium periodate and then reacted with N-(κ-maleimidoundecanoic acid) hydrazide (KMUH).After chelating 188Re with MAG3 group,the SPDP was reduced to PDP and connected onto the maleinimide group at the Fc region.As a result,both the epidermal growth factor receptor vIII (EGFRvIII) targeted monoclonal antibody CH12 and the radionuclide 188Re were conjugated to the HPSA-based vehicles,forming the 188Re-labeled and CH12-tethered HPSA (CH12-HPSA-188Re).The molecular weight and in vitro stability of CH12-HPSA-l88Re were evaluated by gel electrophoresis and paper chromatography.On one hand,the CH12-HPSA-188Re could specifically bind to the EGFRvIII-positive human hepatocarcinoma cells in vitro.On the other hand,it could also target at the tumor tissue of nude mice in vivo.Hence,the CH12-HPSA-188Re could effectively target at the human hepatocarcinoma and facilitate the tumor detection and targeted radioimmunotherapy.

  10. Report on short-term side effects of treatments with {sup 177}Lu-octreotate in combination with capecitabine in seven patients with gastroenteropancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Kam, Boen L.; Kwekkeboom, Dik J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Aken, Maarten O. van [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2008-04-15

    Treatment with the radiolabelled somatostatin analogue {sup 177}Lu-octreotate results in tumour remission in 47% of patients with gastroenteropancreatic neuroendocrine tumours. Adding capecitabine to {sup 177}Lu-octreotate, as a radio-sensitiser, may enhance these anti-tumour effects. We now present the short-term toxicity profile of this novel combination. Seven patients were treated with 7.4 GBq {sup 177}Lu-octreotate and capecitabine (1650 mg/m{sup 2} per day) for 2 weeks with an intended number of four cycles. Toxicity, and especially haematological and renal parameters, were monitored on a weekly basis for the first two cycles and 4 and 6 weeks after subsequent cycles. None of the patients had hand-foot syndrome. One patient had grade 1 stomatitis occurring after one of four cycles. Grade 3 or 4 leukopenia or neutropenia did not occur. One patient had grade 3 anaemia, but none had grade 4 anaemia. One patient had grade 2 thrombocytopenia after the fourth cycle, and one had grade 3 thrombocytopenia. Grade 4 thrombocytopenia did not occur. No significant changes in serum creatinine levels were observed. None of the patients had symptoms of cardiac ischaemia. Treatment with the combination of {sup 177}Lu-octreotate and capecitabine was feasible and safe considering acute and subacute side effects. We therefore started a randomised, controlled clinical trial to compare this combination with {sup 177}Lu-octreotate as single agent with regard to anti-tumour effects and side effects. (orig.)

  11. 177Lu标记单克隆抗体Rituximab及其初步生物学评价%Preparation and Preliminary Biological Evaluation of 177Lu Labelled Rituximab

    Institute of Scientific and Technical Information of China (English)

    马秀凤; 张君丽; 李洪玉; 梁积新; 杨云; 杨春慧; 杜进

    2014-01-01

    以CHX-A'-DTPA和p-SCN-Bz-DTPA为双功能螯合剂,分别对Rituximab进行偶联,用177Lu进行标记,制备177 Lu-Rituximab.在优化条件下,177 Lu对单抗偶联物CHX-A"-DTPA-Rit uximab和p-SCN-Bz-DT-PA-Rituximab的标记率和放化纯度均大于99%.室温及37℃条件下,177Lu-Rituximab在各种测试体系中均显示良好的体外稳定性.在正常小鼠体内的生物分布结果显示,177Lu-Rituximab发生了分解,游离的177Lu在骨中形成较高浓集.177Lu-p-SCN-Bz-DTPA-Rituximab比177Lu-CHX-A"-DTPA-Rituximab的体内清除快,而且游离177 Lu的骨摄取低,结果表明,p-SCN-Bz-DTPA更适于作为双功能螯合剂用于单抗的177Lu标记.

  12. Targeted radiotherapy with {sup 177} Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Energy Technology Data Exchange (ETDEWEB)

    Murphy, M. A de; Pedraza L, M. [Department of Nuclear Medicine, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Mexico D.F. (Mexico); Rodriguez C, J. [Faculty of Medicine, UAEM, Toluca, Estado de Mexico (Mexico); Ferro F, G. [ININ, 52045 Estado de Mexico (Mexico); Murphy S, E. [Hospital Santelena, Mexico D.F. (Mexico)

    2006-07-01

    Malignant pancreas tumours induced in athymic mice are a good model for targeted radiotherapy. The objective of this research was to estimate pancreatic tumour absorbed radiation doses and to evaluate {sup 177}Lu-DOTA-TATE as a therapeutic radiopharmaceutical that could be used in humans. AR42J murine pancreas cancer cells, which over-express somatostatin receptors, were injected in athymic mice and 20 days later the mean tumour size was 3.08 square cm (n=3). A mean of 86.3 MBq {sup 177}Lu-DOTA-TATE, was injected in a tail vein and 19 days after therapy the size of the tumours was 0.81 square cm. There was a partial relapse and after 16 days, when sacrificed, the mean tumour size was 8.28 cubic cm. An epithelial and sarcoma mixed tumour in the kidney of one treated mouse was found. The tumour of the control mouse was 8.61 cubic cm when sacrificed 14 days after tumour induction. Radiotherapy estimates to the tumours was 35.9-39.7 Gy and the tumours might have been completely reduced with a second therapy dose. These preliminary studies justify further therapeutic and dosimetry estimations to ensure that Lu-{sup 177}-DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

  13. Mechanisms of Cell Killing Response from Low Linear Energy Transfer (LET Radiation Originating from 177Lu Radioimmunotherapy Targeting Disseminated Intraperitoneal Tumor Xenografts

    Directory of Open Access Journals (Sweden)

    Kwon Joong Yong

    2016-05-01

    Full Text Available Radiolabeled antibodies (mAbs provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day a suitable radionuclide for radioimmunotherapy (RIT of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB, caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease.

  14. Preparation and preliminary studies on {sup 177}Lu-labeled hydroxyapatite particles for possible use in the therapy of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chakraborty, Sudipta; Das, Tapas [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Sarma, Haladhar D. [Radiation Biology and Health Sciences Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Banerjee, Sharmila [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)], E-mail: sharmila@barc.gov.in

    2008-07-15

    Introduction: Intra-arterial administration of particulates labeled with suitable {beta}{sup -}-emitting radionuclides has emerged as one of the most successful modality for the treatment of primary and metastatic liver cancer. {sup 177}Lu [T{sub 1/2}=6.73 d, E{sub {beta}}(max)=0.49 MeV, E{sub {gamma}}=208 keV (11%)] could be envisaged as a viable radionuclide for use in liver cancer therapy with wider acceptability owing to its feasibility of production in large-scale and relatively longer half-life providing logistic advantages. Hydroxyapatite (HA) particles of 20-60 {mu}m size range are chosen as the particulate carrier due to its excellent biocompatibility and ease of labeling with lanthanides. Methods: {sup 177}Lu was produced by thermal neutron bombardment on enriched Lu target. HA particles of desired size range were synthesized and characterized. Radiolabeling of HA particles was achieved at room temperatures within 30 min. The biological behavior of {sup 177}Lu-labeled HA particles prepared under optimized conditions was tested in Wistar rats. Results: {sup 177}Lu was produced with a specific activity of 444.2{+-}41.8 GBq/mg and radionuclidic purity of 99.98%. {sup 177}Lu-HA was prepared with high radiochemical purity of >99%, and the radiolabeled agent showed excellent in vitro stability. The agent exhibited {approx}73% retention of injected activity in liver after 14 days postadministration with insignificant uptake in any other major organ/tissue except skeleton in biodistribution and imaging studies. Conclusion: {sup 177}Lu-HA exhibited promising features in radiochemical studies. However, preliminary biodistribution studies in normal Wistar rats exhibited suboptimum liver retention and an undesirable skeletal uptake.

  15. Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE of neuroendocrine tumours refractory to conventional therapy

    Energy Technology Data Exchange (ETDEWEB)

    Seregni, E.; Maccauro, M.; Chiesa, C.; Pascali, C.; Lorenzoni, A.; Bogni, A.; Coliva, A.; Bombardieri, E. [Fondazione IRCCS Istituto Nazionale Tumori, Nuclear Medicine, Milan (Italy); Mariani, L.; Vullo, S.Lo [Fondazione IRCCS Istituto Nazionale Tumori, Statistics and Biometry Unit, Milan (Italy); Mazzaferro, V. [Fondazione IRCCS Istituto Nazionale Tumori, Surgery and Liver Transplantation, Milan (Italy); De Braud, F.; Buzzoni, R. [Fondazione IRCCS Istituto Nazionale Tumori, Medical Oncology, Milan (Italy); Milione, M. [Fondazione IRCCS Istituto Nazionale Tumori, Pathology Department, Milan (Italy)

    2014-02-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues has been demonstrated to be an effective therapeutic option in patients with disseminated neuroendocrine tumours (NET). Treatment with tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE may improve the efficacy of PRRT without increasing the toxicity. In a phase II study we evaluated the feasibility of combined PPRT with a high-energy beta emitter ({sup 90}Y) and a medium-energy beta/gamma emitter ({sup 177}Lu) in patients with metastatic NET refractory to conventional therapy. A group of 26 patients with metastatic NET were treated with four therapeutic cycles of alternating [{sup 177}Lu]DOTA-TATE (5.55 GBq) and [{sup 90}Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [{sup 177}Lu]DOTA-TATE to calculate the absorbed doses in healthy organs. The acute and long-term toxicities of repeated treatment were analysed. PRRT efficacy was evaluated according to RECIST. Administration of tandem [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE induced objective responses in 42.3 % of patients with metastatic NET with a median progression-free survival longer than 24 months. Of patients with pretreatment carcinoid syndrome, 90 % showed a symptomatic response or a reduction in tumour-associated pain. The cumulative biologically effective doses (BED) were below the toxicity limit in the majority of patients, in the absence of renal function impairment The results of our study indicates that combined [{sup 90}Y]DOTA-TATE and [{sup 177}Lu]DOTA-TATE therapy is a feasible and effective therapeutic option in NET refractory to conventional therapy. Furthermore, the absence of kidney damage and the evaluated cumulative BEDs suggest that increasing the number of tandem administrations is an interesting approach. (orig.)

  16. High treatment efficacy by dual targeting of Burkitt's lymphoma xenografted mice with a {sup 177}Lu-based CD22-specific radioimmunoconjugate and rituximab

    Energy Technology Data Exchange (ETDEWEB)

    Weber, Tobias; Boetticher, Benedikt; Keller, Armin; Schlegelmilch, Anne; Jaeger, Dirk; Krauss, Juergen [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); Mier, Walter; Kraemer, Susanne; Leotta, Karin [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); Sauter, Max; Haberkorn, Uwe [Heidelberg University Hospital, Department of Nuclear Medicine, Heidelberg (Germany); German Cancer Research Center (DKFZ), Clinical Cooperation Unit Nuclear Medicine, Heidelberg (Germany); Grosse-Hovest, Ludger [University of Tuebingen, Department of Immunology, Tuebingen (Germany); Arndt, Michaela A.E. [Heidelberg University Hospital, Department of Medical Oncology, National Center for Tumor Diseases, Heidelberg (Germany); German Cancer Research Center (DKFZ), Immunotherapy Program, National Center for Tumor Diseases, Heidelberg (Germany)

    2016-03-15

    Dual-targeted therapy has been shown to be a promising treatment option in recurrent and/or refractory B-cell non-Hodgkin's lymphoma (B-NHL). We generated radioimmunoconjugates (RICs) comprising either a novel humanized anti-CD22 monoclonal antibody, huRFB4, or rituximab, and the low-energy β-emitter {sup 177}Lu. Both RICs were evaluated as single agents in a human Burkitt's lymphoma xenograft mouse model. To increase the therapeutic efficacy of the anti-CD22 RIC, combination therapy with unlabelled anti-CD20 rituximab was explored. The binding activity of CHX-A''-DTPA-conjugated antibodies to target cells was analysed by flow cytometry. To assess tumour targeting of {sup 177}Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1{sup null}) interleukin-2 receptor common gamma chain (IL2r γ {sup null}) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. {sup 177}Lu-conjugated antibodies were administered at a single dose of 9.5 MBq per mouse. For dual-targeted therapy, rituximab was injected at weekly intervals (0.5 - 1.0 mg). Tumour accumulation of RICs was monitored by planar scintigraphy. Conjugation of CHX-A''-DTPA resulted in highly stable RICs with excellent antigen-binding properties. Biodistribution experiments revealed higher tumour uptake of the {sup 177}Lu-labelled anti-CD22 IgG than of {sup 177}Lu-labelled rituximab. Treatment with {sup 177}Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with {sup 177}Lu-conjugated rituximab. The therapeutic efficacy of the anti-CD22 RIC could be markedly enhanced by combination with unlabelled rituximab. These findings suggest that dual targeting with {sup 177}Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for

  17. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with {sup 177}Lu-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [Charite, University Medicine Berlin, Campus Virchow Clinic, Department of Hepatology and Gastroenterology, Berlin (Germany); Nagarajah, James [University Hospital, Department of Nuclear Medicine, Essen (Germany)

    2014-03-15

    Renal radiation during peptide receptor radionuclide therapy (PRRT) may result in glomerular damage, a potential reduction of glomerular filtration rate (GFR) and ultimately lead to renal failure. While reported PRRT nephrotoxicity is limited to data derived from serum creatinine - allowing only approximate estimates of GFR - the aim of this study is to accurately determine PRRT-induced long-term changes of renal function and associated risk factors according to state-of-the-art GFR measurement. Nephrotoxicity was analysed using {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with {sup 177}Lu-octreotate. The mean follow-up period was 21 months (range 12-50) with a median of five GFR measurements per patient. The change of GFR was analysed by linear curve fit. Potential risk factors including diabetes mellitus, arterial hypertension, previous chemotherapy, renal impairment at baseline and cumulative administered activity were analysed regarding potential impact on renal function loss. In addition, Common Terminology Criteria for Adverse Events (CTCAE) v3.0 were used to compare nephrotoxicity determined by {sup 99m}Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m{sup 2} per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m{sup 2} per year) and 16 patients (22 %) a significant (>10 ml/min/m{sup 2} per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m{sup 2} per year. Relevant nephrotoxicity according to CTCAE (grade ≥3) was observed in one patient (1.3 %) with arterial hypertension and history of chemotherapy. Nephrotoxicity according to serum creatinine was discordant to that defined by GFR in 15 % of the assessments and led to underestimation in 12 % of

  18. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE: the IEO phase I-II study

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M.; Baio, Silvia M.; Lombardo, Dario; Chinol, Marco; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Cremonesi, Marta; Ferrari, Mahila E. [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Fazio, Nicola [European Institute of Oncology, Division of Medical Oncology, Milan (Italy); Iodice, Simona [European Institute of Oncology, Division of Epidemiology and Biostatistics, Milan (Italy); Bartolomei, Mirco [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); M. Bufalini Hospital, Division of Nuclear Medicine, Cesena, FC (Italy); Sansovini, Maddalena [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, Unit of Radiometabolic Medicine, Meldola, FC (Italy)

    2011-12-15

    Peptide receptor radionuclide therapy (PRRT) is used in tumours expressing type 2 somatostatin receptors (sst{sub 2}), mainly neuroendocrine. The aim of this prospective phase I-II study was to evaluate the toxicity and efficacy of {sup 177}Lu-DOTATATE in multiple cycles. Fifty-one consecutive patients with unresectable/metastatic sst{sub 2}-positive tumours, divided into two groups, received escalating activities (3.7-5.18 GBq/cycle, group 1; 5.18-7.4 GBq/cycle, group 2) of {sup 177}Lu-DOTATATE. Cumulative activities ranged from 3.7 to 29.2 GBq (median 26.4 GBq in median 6 cycles, group 1, 21 patients) and 5.55 to 28.9 GBq (median 25.2 GBq in 4 cycles, group 2, 30 patients), based on dosimetry. No major acute or delayed renal or haematological toxicity occurred (one grade 3 leukopenia and thrombocytopenia). Cumulative renal absorbed doses were 8-37 Gy (9-41 Gy bioeffective doses). A median decrease of creatinine clearance of 21.7% 6 months after PRRT, 23.9% after 1 year and 27.6% after 2 years was observed. Higher losses (>20%) occurred in patients with risk factors for renal toxicity, particularly hypertension and diabetes. Cumulative bone marrow doses were <1.5 Gy. Blood elements showed a progressive mild drop during cycles and recovered during follow-up (median 30 months). Thirty-nine patients were progressive at enrolment. Partial and complete responses occurred in 15 of 46 (32.6%) assessable patients. The median time to progression was 36 months. Overall survival was 68% at 36 months. Non-responders and patients with extensive tumour involvement had lower survival. {sup 177}Lu-DOTATATE was well tolerated up to 29 GBq cumulative activity (up to 7.4 GBq/cycle). The maximum tolerated dose/cycle was not reached. However, considering the individual bone marrow function and the presence of risk factors for kidney toxicity, it seems safer to divide cumulative activities into lower activity cycles. (orig.)

  19. Renal function affects absorbed dose to the kidneys and haematological toxicity during {sup 177}Lu-DOTATATE treatment

    Energy Technology Data Exchange (ETDEWEB)

    Svensson, Johanna; Berg, Gertrud [Sahlgrenska University Hospital, Department of Oncology, Goeteborg (Sweden); Waengberg, Bo [Sahlgrenska University Hospital, Department of Surgery, Goeteborg (Sweden); Larsson, Maria [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Forssell-Aronsson, Eva; Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Institute of Clinical Sciences, The Sahlgrenska Academy, Goeteborg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengineering, Goeteborg (Sweden)

    2015-05-01

    Peptide receptor radionuclide therapy (PRRT) has become an important treatment option in the management of advanced neuroendocrine tumours. Long-lasting responses are reported for a majority of treated patients, with good tolerability and a favourable impact on quality of life. The treatment is usually limited by the cumulative absorbed dose to the kidneys, where the radiopharmaceutical is reabsorbed and retained, or by evident haematological toxicity. The aim of this study was to evaluate how renal function affects (1) absorbed dose to the kidneys, and (2) the development of haematological toxicity during PRRT treatment. The study included 51 patients with an advanced neuroendocrine tumour who received {sup 177}Lu-DOTATATE treatment during 2006 - 2011 at Sahlgrenska University Hospital in Gothenburg. An average activity of 7.5 GBq (3.5 - 8.2 GBq) was given at intervals of 6 - 8 weeks on one to five occasions. Patient baseline characteristics according to renal and bone marrow function, tumour burden and medical history including prior treatment were recorded. Renal and bone marrow function were then monitored during treatment. Renal dosimetry was performed according to the conjugate view method, and the residence time for the radiopharmaceutical in the whole body was calculated. A significant correlation between inferior renal function before treatment and higher received renal absorbed dose per administered activity was found (p < 0.01). Patients with inferior renal function also experienced a higher grade of haematological toxicity during treatment (p = 0.01). The residence time of {sup 177}Lu in the whole body (range 0.89 - 3.0 days) was correlated with grade of haematological toxicity (p = 0.04) but not with renal absorbed dose (p = 0.53). Patients with inferior renal function were exposed to higher renal absorbed dose per administered activity and developed a higher grade of haematological toxicity during {sup 177}Lu-DOTATATE treatment. The study confirms the

  20. Preliminary study of metabolic radiotherapy with {sup 188}Re via small animal imaging

    Energy Technology Data Exchange (ETDEWEB)

    Antoccia, A. [Dept. of Biology, Univ. Roma3, V.le G. Marconi, I-00146 Rome (Italy); INFN, Sezione Roma3, Via della Vasca Navale 84, I-00146 Rome (Italy); Baldazzi, G. [Dept. of Physics, Univ. Bologna, V.le C. Berti-Pichat 6/2, I-40127 Bologna (Italy); INFN, Sezione Bologna, V.le C. Berti-Pichat 6/2, I-40127 Bologna (Italy); Bello, M. [Dept. of Physics, Univ. Padova, Via F. Marzolo 8, I-35131 Padova (Italy); INFN - LNL, V.le dell' Universita 2, I-35020 Legnaro(Italy)

    2006-01-15

    {sup 188}Re is a {beta}{sup -} (Emax=2.12 MeV) and {gamma} (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, {sup 99m}Tc, molecules of hyaluronic acid (HA) have been labelled with {sup 188}Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm{sup 3} pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of {sup 188}Re and with C57 black mice injected with the {sup 188}Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at 90 degrees. They use a CsI(Tl) matrix with 1x1x5 mm{sup 3} pixels read out by H8500 Hamamatsu Flat panel PMT.

  1. Preliminary study of metabolic radiotherapy with 188Re via small animal imaging

    CERN Document Server

    Baldazzi, G; Muciaccio, A; Navarria, Francesco Luigi; Pancaldi, G; Perrotta, A; Zuffa, M; Boccaccio, P; Uzunov, N; Bello, M; Bernardini, D; Mazzi, U; Moschini, G; Riondato, M; Rosato, A; Garibaldi, F; Pani, R; Antoccia, A; De Notaristefani, F; Hull, G; Cencelli, V O; Sgura, A; Tanzarella, C

    2006-01-01

    188Re is a beta- (Emax = 2.12 MeV) and gamma (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, 99mTc, molecules of hyaluronic acid (HA) have been labelled with 188Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm**3 pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of 188Re and with C57 black mice injected with the 188Re-HA solution are presented. To increase the space resolution and to obtain two orthogonal projections simultaneously we are building in parallel two new cameras to be positioned at...

  2. Formulation, radiopharmaceutical kinetics and dosimetry of the {sup 188}Re(V)-DMSA complex; Formulacion, radiofarmacocinetica y dosimetria del complejo {sup 188}Re(V)-DMSA

    Energy Technology Data Exchange (ETDEWEB)

    Garcia S, L.; Ferro F, G. [Departamento de Materiales Radiactivos. Instituto Nacional de Investigaciones Nucleares, C.P. 52045 Salazar, Estado de Mexico (Mexico); Murphy, C.A. de; Pedraza L, M. [Departamento de Medicina Nuclear, Instituto Nacional de la Nutricion, Salvador Zubiran, Mexico D.F. (Mexico); Azorin N, J. [Departamento de Fisica, Universidad Autonoma Metropolitana Iztapalapa, Mexico D.F. (Mexico)

    1999-07-01

    It was developed through experimental design (ANOVA), a formulation to prepare the {sup 188} Re(V)-Dmsa complex. Likewise, there were realized studies of radiopharmaceutical kinetics and internal dosimetry in animals, its normal and with induced tumors, considering an open bi compartmental model using the MIRD methodology. The {sup 188} Re(V)-Dmsa complex was obtained with a radiochemical purity greater than 95% incubating 30 min at 90 Centigrade under the following formulation: [SnCl{sub 2}] = 1.4 mg/ml, [ascorbic acid] = 0.5 mg/ml, p H = 2.0 - 3.0. The stability test of the formulation, shows that after 48 h of its preparation, does not produce radiolytic degradation neither chemical decomposition. The radiopharmaceutical kinetics data show an average residence time 7.2h, velocity constant {alpha} = 0.6508h{sup -1} and {beta} = 0.1046 h{sup -1} with an apparent distribution volume 6.9 l. The main elimination via was renal and it was observed osseous caption with an accumulated activity 522.049 {+-} 62 MBq h (residence time 14.1094 {+-} 1.69h). In according with the dosimetric calculations, by each 37 MBq injected, the equivalent dose at the tumor was 9.67{+-} 0.33 Sv/g, for an effective dose 0.292 {+-} 0.0017 mSv/MBq. The images obtained in the gamma camera of the mice with induced tumors, show that do not have significant accumulation in the metabolic organs. The caption in bone and in tumors induced of the {sup 188} Re(V)-Dmsa complex, show its potential for be used as a palliative agent for pain in patients with osseous metastasis and in the treatment of tumors of soft tissue. (Author)

  3. Effects of therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate on endocrine function

    Energy Technology Data Exchange (ETDEWEB)

    Teunissen, Jaap J.M.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de [Erasmus Medical Center, Department of Internal Medicine, Rotterdam (Netherlands); Rijke, Yolanda B. de [Erasmus Medical Center, Department of Clinical Chemistry, Rotterdam (Netherlands)

    2009-11-15

    Peptide receptor radionuclide therapy (PRRT) with radiolabelled somatostatin analogues is a novel therapy for patients with somatostatin receptor-positive tumours. We determined the effects of PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate) on glucose homeostasis and the pituitary-gonadal, pituitary-thyroid and pituitary-adrenal axes. Hormone levels were measured and adrenal function assessed at baseline and up to 24 months of follow-up. In 35 men, mean serum inhibin B levels were decreased at 3 months post-therapy (205 {+-} 16 to 25 {+-} 4 ng/l, p < 0.05) and follicle-stimulating hormone (FSH) levels increased (5.9 {+-} 0.5 to 22.7 {+-} 1.4 IU/l, p < 0.05). These levels returned to near baseline levels. Total testosterone and sex hormone binding globulin (SHBG) levels decreased (15.0 {+-} 0.9 to 10.6 {+-} 1.0 nmol/l, p < 0.05 and 61.8 {+-} 8.7 to 33.2 {+-} 3.7 nmol, p < 0.05), respectively, whereas non-SHBG-bound T did not change. An increase (5.2 {+-} 0.6 to 7.7 {+-} 0.7 IU/l, p < 0.05) of luteinizing hormone (LH) levels was found at 3 months of follow-up returning to baseline levels thereafter. In 21 postmenopausal women, a decrease in levels of FSH (74.4 {+-} 5.6 to 62.4 {+-} 7.7 IU/l, p < 0.05) and LH (26.8 {+-} 2.1 to 21.1 {+-} 3.0 IU/l, p < 0.05) was found. Of 66 patients, 2 developed persistent primary hypothyroidism. Free thyroxine (FT{sub 4}) levels decreased (17.7 {+-} 0.4 to 15.6 {+-} 0.6 pmol/l, p < 0.05), whereas thyroid-stimulating hormone (TSH) and triiodothyronine (T{sub 3}) levels did not change. Reverse triiodothyronine (rT{sub 3}) levels decreased (0.38 {+-} 0.03 to 0.30 {+-} 0.01 nmol/l, p < 0.05). Before and after therapy adrenocorticotropic hormone (ACTH) stimulation tests showed an adequate response of serum cortisol (> 550 nmol/l, n = 18). Five patients developed elevated HbA{sub 1c} levels (> 6.5%). In men {sup 177}Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non

  4. Dosimetric evaluation of anti-CD20 labelled with {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, Graciela; Osso Junior, Joao A., E-mail: gracielabarrio@usp.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    Radioimmunotherapy has the potential to deliver lethal radiation energy directly to malignant cells via targeting of radioisotope-conjugated monoclonal antibodies (MAbs) to specific antigens. B-cell lymphoma is a particularly good candidate for radioimmunotherapy because the disease is inherently radiosensitive, malignant cells in the blood, bone marrow, spleen and lymphonodes are accessible, and MAbs have been developed to B-cell surface antigens that do not shed or modulate. Rituximab (RTX), the human IgG1-type chimeric form of the parent murine antibody ibritumomab, is specifically targeted against CD20, a surface antigen expressed by pre-B and mature human B lymphocytes. The use of rhenium-188 from a {sup 188}W/{sup 188}Re generator system represents an attractive alternative radionuclide for therapy. {sup 188}Re is produced from beta decay of the {sup 188}W parent. In addition to the emission of high-energy electrons (E{beta}= 2118 keV), {sup 188}Re also decays with emission of a gamma photon with an energy of 155 keV in 15% abundance. Besides the therapeutic usefulness of {sup 188}Re, the emission of gamma photon is an added advantage since the biodistribution of {sup 188}Re-labeled antibodies can be evaluated in vivo with a gamma camera. Also, rhenium has chemical properties similar to technetium. Thus, both can be conjugated to antibodies using similar chemistry methods. The objective of this work is to prove the usefulness of this radiopharmaceutical based on dosimetric studies, that are also required by the Brazilian Regulatory Agency (ANVISA). (author)

  5. Labeling of MDP with {sup 188}Re for bone tumour therapy

    Energy Technology Data Exchange (ETDEWEB)

    Barbezan, Angelica B.; Osso Junior, Joao A., E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    {sup 188}Re is one of the most attractive radioisotopes for a variety of therapeutic applications in nuclear medicine, due to its physical decay properties, such as {beta}{sup -} emission of 2.12 MeV, {gamma} emission of 155 keV and half life of 16.9 hours. Biphosphonates are potent inhibitors of osteoclastic bone resorption and are effective in several diseases that cause bone fragility and bone metastases. Because of these characteristics, labeled biphosphonates have been studied for bone pathologies, also acting as palliation of bone pain in case of metastasis.The aim of this study was to optimize the labeling of a phosphonate-MDP (Sodium Methylene Diphosphonate) with {sup 188}Re for use in bone pain palliation. {sup 188}Re was obtained by eluting a {sup 188}W-{sup 188}Re generator from POLATOM. The labeling was performed at room temperature using MDP, SnCl{sub 2} as reducing agent and ascorbic acid. The variables studied were: Mass of ligand (3, 6 and 10 mg), reducing agent mass (5, 7, 10 and 11 mg), ascorbic acid mass (1, 3, 5 and 6 mg), pH (1 and 2) and time of reaction (15, 60, 120, 360 and 4320 minutes), that also reflected the stability of the radiopharmaceutical. The radiochemical control, that also measures the labeling efficiency was evaluated by paper chromatography using Whatman 3MM paper and the solvents acetone and 0.9%NaCl. The best formulation was the following: Mass of ligand MDP: 10 mg, mass of SnCl{sub 2}: 5 mg, ascorbic acid mass: 3 mg, time of reaction: 30 minutes, pH: 1. Under optimum conditions, {sup 188}Re MDP radiolabeling yield was 98,07% and the radiopharmaceutical was stable up to 72 h. (author)

  6. Optimization of radioimmunotherapy of renal cell carcinoma: labeling of monoclonal antibody cG250 with 131I, 90Y, 177Lu, or 186Re.

    NARCIS (Netherlands)

    Brouwers, A.H.; Eerd-Vismale, J.E.M. van; Frielink, C.; Oosterwijk, E.; Oyen, W.J.G.; Corstens, F.H.M.; Boerman, O.C.

    2004-01-01

    Radioimmunotherapy (RIT) can be performed with various radionuclides. We tested the stability, biodistribution, and therapeutic efficacy of various radioimmunoconjugates ((131)I, (88/90)Y, (177)Lu, and (186)Re) of chimeric antirenal cell cancer monoclonal antibody G250 (mAb cG250) in nude mice with

  7. An approach for conjugation of 177 Lu- DOTA-SCN- Rituximab (BioSim & its evaluation for radioimmunotherapy of relapsed & refractory B-cell non Hodgkins lymphoma patients

    Directory of Open Access Journals (Sweden)

    Parul Thakral

    2014-01-01

    Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim in patients of relapsed and refractory non Hodgkin′s lymphoma can be considered.

  8. {sup 177}Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Rasaneh, Samira [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Rajabi, Hossein, E-mail: hrajabi@modares.ac.i [Department of Medical Physics, Faculty of Medical Sciences, Tarbiat Modares University, P.O. Box 14115-331, Tehran (Iran, Islamic Republic of); Babaei, Mohammad Hossein; Daha, Fariba Johari [Department of Radioisotope, Nuclear Science and Technology Research Institute, 14115-331 Tehran (Iran, Islamic Republic of)

    2010-11-15

    Introduction: In the present study, Herceptin was labeled with lutetium-177 via DOTA, and the necessary preclinical quality control tests (in vitro and in vivo) were performed to evaluate its use as a radioimmunotherapy agent. Material and Methods: Herceptin was conjugated to DOTA as a chelator in three different conjugation buffers (ammonium acetate, carbonate and HEPES buffer); each of the resulting conjugates was compared with respect to in vitro characteristics such as number of chelates per antibody, incorporated activity, immunoreactivity and in vitro stability in PBS buffer and blood serum. The biodistribution study and gamma camera imaging were performed in mice bearing breast tumors. To assess the therapeutic effects of {sup 177}Lu-Herceptin, cytotoxicity was investigated for 7 days in a SKBr3 breast cancer cell line. Results: Carbonate buffer was the best conjugation buffer (number of chelates per antibody: 6; incorporated activity: 81%; immunoreactivity: 87%; buffer stability: 86%; serum stability: 81%, after 4 days). The efficient tumor uptake observed in the biodistribution studies was consistent with the gamma camera image results. At a concentration of 4 {mu}g ml{sup -1}, {sup 177}Lu-Herceptin (surviving cells: 5{+-}0.6% of the total cells) of the total cells corresponded to an approximately eightfold increase in cytotoxicity in comparison to unmodified Herceptin (surviving cells: 43{+-}3.9%). Conclusion: The new complex described herein could be considered for further evaluation in animals and potentially in humans as a radiopharmaceutical for use in the radioimmunotherapy of breast cancer. These results may be important for patients who cannot tolerate the therapeutic dosage of Herceptin currently used because of heart problems.

  9. Outcome and toxicity of salvage therapy with {sup 177}Lu-octreotate in patients with metastatic gastroenteropancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Haslerud, Torjan; Sabet, Amin; Ahmadzadehfar, Hojjat; Guhlke, Stefan; Biersack, Hans-Juergen; Ezziddin, Samer [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Pape, Ulrich-Frank [University Medicine Berlin, Department of Hepatology and Gastroenterology, Charite, Campus Virchow Clinic, Berlin (Germany); Gruenwald, Frank [University Hospital, Department of Nuclear Medicine, Frankfurt (Germany)

    2014-02-15

    We assessed the outcome and toxicity of salvage therapy (repeat treatment) with {sup 177}Lu-octreotate and high cumulative activities in patients with metastatic gastroenteropancreatic neuroendocrine tumours (GEP-NET). We retrospectively analysed a consecutive cohort of 33 patients with metastatic GEP-NET who underwent salvage peptide receptor radionuclide therapy (PRRT) in our institution. All patients had progressive NET prior to salvage treatment and had shown an initial response to PRRT. The mean cumulative activity was 44.3 GBq (30.0-83.7 GBq). Radiographic response was assessed using CT and/or MRI according to modified SWOG criteria. Toxicity was evaluated using laboratory data, including complete blood counts and renal function tests using CTCAE 3.0. Survival analysis was performed with the Kaplan-Meier curve method and a significance level at p < 0.05. Radiographic responses consisted of complete response in 1 patient (3.0 %), partial response in 6 patients (18.2 %), minor response in 1 patient (3.0 %), stable disease in 14 patients (42.4 %), and progressive disease in 11 patients (33.3 %). Median progression-free survival (PFS) from the start of salvage therapy was 13 months (95 % CI 9-18) and patients with a history of a durable PFS after initial PRRT tended to have long-lasting PFS after salvage treatment (p = 0.04). None of the patients developed severe nephrotoxicity (grade 3/4) or a myelodysplastic syndrome during follow-up. Relevant albeit reversible haematotoxicity (grade 3/4) occurred in 7 patients (21.2 %). The cumulative administered activity was not associated with an increased incidence of haematotoxicity. PRRT with {sup 177}Lu-octreotate in the re-treatment setting is safe and effective in patients with metastatic GEP-NET. (orig.)

  10. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with {sup 177}Lu for tumors therapy that expressing αβ integrin s; Sistema monomerico, dimerico y multimerico de peptidos de RGD radiomarcados con {sup 177}Lu para terapia de tumores que expresan integrinas αβ

    Energy Technology Data Exchange (ETDEWEB)

    Luna G, M. A.

    2014-07-01

    The conjugation of peptides to gold nanoparticles (AuNPs) produces biocompatible and stable multimeric systems with target-specific molecular recognition. Peptides based on the cyclic Arg-Gly-Asp (RGD) sequence have been reported as high affinity agents for the α(v)β(3) and α(v)β(5) integrin. The aim of this research was to prepare a multimeric system of {sup 177}Lu-labeled gold nanoparticles conjugated to c[RGDfK(C)] [cyclo(Arg-Gly-Asp-Phe-Lys(Cys)] peptides and to compare the radiation absorbed dose with that of {sup 177}Lu-labeled monomeric and dimeric RGD peptides to α(v)β(3) integrin-positive U87MG tumors in mice, as well as, evaluate the in vitro potential {sup 177}Lu-AuNP-c[RGDfK(C)] as a plasmonic photothermal therapy and targeted radiotherapy system in MCF7 breast cancer cells. DOTA-GGC (1,4,7,10-tetraaza cyclododecane-N,N,N-tetraacetic-Gly-Gly-Cys) and c[RGDfK(C)] peptides were synthesized and conjugated to AuNPs by the spontaneous reaction of the thiol groups. Tem, UV-Vis, XP S, Raman and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with the peptides. To obtain {sup 177}Lu-AuNP-c[RGDfK(C)], the {sup 177}Lu-DOTA-GGC radio peptide was first prepared and added to a solution of AuNPs followed by c[RGDfK(C)] (25 μL, 5 μM) at 18 grades C for 15 min. {sup 177}Lu-DOTA-GGC, {sup 177}Lu- DOTA-cRGDfK and {sup 177}Lu-DOTA-E-c(RGDfK){sub 2} were prepared by adding {sup 177}LuCl{sub 3} (370 MBq) to 5 μL (1 mg/ml) of the DOTA derivative diluted with 50 μL of 1 M acetate buffer at ph 5. The mixture was incubated at 90 grades C in a block heater for 30 min. Radiochemical purity was determined by ultrafiltration and HPLC analyses. After laser irradiation, the presence of c[RGDfK(C)]-AuNP in cells caused a significant increase in the temperature of the medium (50.5 grades C, compared to 40.3 grades C without AuNPs) resulting in a significant decrease in MCF7 cell viability down to 9 %. After treatment with {sup 177}Lu

  11. Anti-CD45 radioimmunotherapy with 90Y but not 177Lu is effective treatment in a syngeneic murine leukemia model.

    Directory of Open Access Journals (Sweden)

    Johnnie J Orozco

    Full Text Available Radioimmunotherapy (RIT for treatment of hematologic malignancies has primarily employed monoclonal antibodies (Ab labeled with 131I or 90Y which have limitations, and alternative radionuclides are needed to facilitate wider adoption of RIT. We therefore compared the relative therapeutic efficacy and toxicity of anti-CD45 RIT employing 90Y and 177Lu in a syngeneic, disseminated murine myeloid leukemia (B6SJLF1/J model. Biodistribution studies showed that both 90Y- and 177Lu-anti-murine CD45 Ab conjugates (DOTA-30F11 targeted hematologic tissues, as at 24 hours 48.8 ± 21.2 and 156 ± 14.6% injected dose per gram of tissue (% ID/g of 90Y-DOTA-30F11 and 54.2 ± 9.5 and 199 ± 11.7% ID/g of 177Lu-DOTA-30F11 accumulated in bone marrow (BM and spleen, respectively. However, 90Y-DOTA-30F11 RIT demonstrated a dose-dependent survival benefit: 60% of mice treated with 300 µCi 90Y-DOTA-30F11 lived over 180 days after therapy, and mice treated with 100 µCi 90Y-DOTA-30F11 had a median survival 66 days. 90Y-anti-CD45 RIT was associated with transient, mild myelotoxicity without hepatic or renal toxicity. Conversely, 177Lu- anti-CD45 RIT yielded no long-term survivors. Thus, 90Y was more effective than 177Lu for anti-CD45 RIT of AML in this murine leukemia model.

  12. In vitro characterization of {sup 177}Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Lohri, Andreas [Basel University Medical Clinic, Liestal (Switzerland); Moldenhauer, Gerhard [German Cancer Research Center, Division of Molecular Immunology, Heidelberg (Germany)

    2009-09-15

    {sup 131}I- and {sup 90}Y-labelled anti-CD20 antibodies have been shown to be effective in the treatment of low-grade, B-cell non-Hodgkin's lymphoma (NHL). However, the most appropriate radionuclide in terms of high efficiency and low toxicity has not yet been established. In this study we evaluated an immunoconjugate formed by the anti-CD20 antibody rituximab and the chelator DOTA (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid). DOTA-rituximab was prepared as a kit formulation and can be labelled in a short time (<20 min) with either {sup 177}Lu or {sup 90}Y. Immunoconjugates with different numbers of DOTA molecules per rituximab were prepared using p-SCN-Bz-DOTA. In vitro immunoreactivity and stability were tested and preliminary dosimetric results were acquired in two patients. The immunological binding properties of DOTA-rituximab to the CD20 antigen were found to be retained after conjugation with up to four chelators. The labelled product was stable against a 10{sup 5} times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m{sup 2} body surface {sup 177}Lu-DOTA-rituximab. Scintigraphic images showed specific uptake at tumour sites and acceptable dosimetric results. The mean whole-body dose was found to be 314 mGy. The administration of {sup 177}Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with {sup 177}Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. {sup 177}Lu-DOTA-rituximab is an interesting, well-tolerated radiolabelled antibody with clinical activity in a low dose range, and provides an approach to the efficient treatment with few side effects for patients with relapsed NHL. (orig.)

  13. Assessment of 188Re marked anti MHC class Ⅱ antibody by peripheral blood mononuclear cells stimulated by donor alloantigen

    Institute of Scientific and Technical Information of China (English)

    DING Guo-ping; CAO Li-ping; LIU Jie; LIU Da-ren; QUE Ri-sheng; ZHU Lin-hua; ZHOU Yi-ming; MAO Ke-jie; HU Jun-an

    2011-01-01

    Background Previous studies showed that anti MHC-Ⅱ monoclone antibody (MAb) only had partial inhibiting effect of alloreactive mixed lymphocyte reaction (MLR) in vitro and it was unsteady and non-persistent. The aim of this research was to determine whether radioactive isotope 188Re marked MHC-Ⅱ antibody could benefit the allograft acceptance in transplantation as compared to normal MHC-Ⅱ antibody.Methods 188Re was incorporated to 2E9/13F(ab')2 which is against swine MHC class Ⅱ antigen (MAb-188Re). Porcine peripheral blood mononuclear (PBMC) cells were examined for proliferation and cytokine mRNA expression after stimulation with MHC-Ⅱ MAb or MAb-188Re.Results The proliferative response of recipient PBMCs in mixed lymphocyte reaction (MLR) to donor alloantigen showed that the stimulation index of MAb-188Re group was significantly lower than the MHC-Ⅱ MAb group and control (P<0.05). mRNA expression of interleukin 2, interferon Y and tumor necrosis factor α (type 1 cytokines) was lower in MAb-188Re group than the MHC-Ⅱ MAb group, while interleukin 10 (type 2 cytokines) was higher in MAb-188Re group in the first 24 hours.Conclusion MAb-188Re could help the graft acceptance by inhibiting T cell proliferation, lowering the expression of type 1 cytokines and elevating the type 2 cytokines produced by PBMC.

  14. In vivo examination of {sup 188}Re(I)-tricarbonyl-labeled trastuzumab to target HER2-overexpressing breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Chen, K.-T. [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Lee, T.-W. [Institute of Nuclear Energy Research, Longtan 32546, Taiwan (China); Lo, Jem-Mau [Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan (China); Institute of Nuclear Engineering and Science, National Tsing Hua University, Hsinchu 30013, Taiwan (China)], E-mail: jmlo@mx.nthu.edu.tw

    2009-05-15

    Introduction: Trastuzumab (Herceptin), a humanized IgG1 monoclonal antibody directed against the extracellular domain of the HER2 protein, acts as an immunotherapeutic agent for HER2-overexpressing human breast cancers. Radiolabeled trastuzumab with {beta}- or {alpha} emitters can be used as radioimmunotherapeutic agent for the similar purpose but with additional radiation effect. Methods: In this study, trastuzumab was labeled with {sup 188}Re for radioimmunotherapy of HER2/neu-positive breast cancer. {sup 188}Re(I)-tricarbonyl ion, [{sup 188}Re(OH{sub 2}){sub 3}(CO){sub 3}]{sup +}, was employed as a precursor for directly labeling the monoclonal antibody with {sup 188}Re. The immunoreactivity of {sup 188}Re(I)-trastuzumab was estimated by competition receptor-binding assay using HER2/neu-overexpressive BT-474 human breast cancer cells. The localization properties of {sup 188}Re(I)-trastuzumab within both tumor and normal tissues of athymic mice bearing BT-474 human breast cancer xenografts (HER2/neu-overexpressive) and similar mice bearing MCF-7 human breast cancer xenografts (HER2/neu-low expressive) were investigated. Results: When incubated with human serum albumin and histidine at 25{sup o}C, {sup 188}Re(I)-trastuzumab was found to be stable within 24 h. The IC{sub 50} of {sup 188}Re(I)-trastuzumab was found to be 22.63{+-}4.57 nM. {sup 188}Re(I)-trastuzumab was shown to accumulate specifically in BT-474 tumor tissue in in vivo biodistribution studies. By microSPECT/CT, the image of {sup 188}Re localized BT-474 tumor was clearly visualized within 24 h. In contrast, {sup 188}Re(I)-trastuzumab uptake in HER2-low-expressing MCF-7 tumor was minimal, and the {sup 188}Re image at the localization of the tumor was dim. Conclusion: These results reveal that {sup 188}Re(I)-trastuzumab could be an appropriate radioimmunotherapeutic agent for the treatment of HER2/neu-overexpressing cancers.

  15. Preparation and quality control of clinic scale {sup 188}W-{sup 188}Re generator

    Energy Technology Data Exchange (ETDEWEB)

    Yin, Duanzhi; Zhou, Wei [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Hu, Weiqing; He, Weiyu; Zhang, Lei; Min, Xiafeng; Shi, Xichang; Cao, Benhong [Amersham Kexin Pharmaceutical Co. Ltd, Shanghai (China); Wang, Yongxian [Chinese Academy of Sciences, Shanghai (China). Shanghai Inst. of Applied Physics; Amersham Kexin Pharmaceutical Co. Ltd, Shanghai (China)

    2004-07-01

    {sup 188}Re is an excellent candidate for the radionuclide therapy, since it is easily obtained as a ''no-carrier-added'' radioisotope from a {sup 188}W-{sup 188}Re generator. The half-life of 16.9 hours is suitable for tumor treatment and of benefit to minimize toxicity to whole body; Beta emissions with energies of 2.12 MeV (71.6%) and 1.97 MeV (25.1%) are suitable for therapy and the gamma emission of 155 keV (15%) allows imaging and dosimetry. The drug for tumor therapy has been a highlight of the new drug development in recent years. The radionuclide therapy has shown significant effectiveness in the treatment of various cancers. {sup 188}W-{sup 188}Re generator could conveniently provide high levels of carrier-free rhenium-188 at low cost for the treatment of a variety of cancers, cardiovascular diseases as well as the marrow transplantation. (orig.)

  16. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Vermeij, Marcel [Erasmus MC, Department of Pathology, Rotterdam (Netherlands)

    2007-05-15

    In peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues, the kidneys are the major dose-limiting organs, because of tubular reabsorption and retention of radioactivity. Preventing renal uptake or toxicity will allow for higher tumour radiation doses. We tested the cytoprotective drug amifostine, which selectively protects healthy tissue during chemo- and radiotherapy, for its renoprotective capacities after PRRT with high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Male Lewis rats were injected with 278 or 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate to create renal damage and were followed up for 130 days. For renoprotection, rats received either amifostine or co-injection with lysine. Kidneys, blood and urine were collected for toxicity measurements. At 130 days after PRRT, a single-photon emission computed tomography (SPECT) scan was performed to quantify tubular uptake of {sup 99m}Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate resulted in body weight loss, elevated creatinine and proteinuria. Amifostine and lysine treatment significantly prevented this rise in creatinine and the level of proteinuria, but did not improve the histological damage. In contrast, after 278 MBq [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, creatinine values were slightly, but not significantly, elevated compared with the control rats. Proteinuria and histological damage were different from controls and were significantly improved by amifostine treatment. Quantification of {sup 99m}Tc-DMSA SPECT scintigrams at 130 days after [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate therapy correlated well with 1/creatinine (r {sup 2} = 0.772, p < 0.001). Amifostine and lysine effectively decreased functional renal damage caused by high-dose [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well

  17. Direct in vitro and in vivo comparison of {sup 161}Tb and {sup 177}Lu using a tumour-targeting folate conjugate

    Energy Technology Data Exchange (ETDEWEB)

    Mueller, Cristina; Reber, Josefine; Haller, Stephanie [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger; Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Laboratory of Radiochemistry and Environmental Chemistry, Department of Chemistry and Biochemistry, Bern (Switzerland); Bernhardt, Peter [The Sahlgrenska Academy, University of Gothenburg, Department of Radiation Physics, Gothenburg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Medical Bioengeneering, Gothenburg (Sweden); Zhernosekov, Konstantin [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2014-03-15

    The radiolanthanide {sup 161}Tb (T{sub 1/2} = 6.90 days, Eβ{sup -}{sub av} = 154 keV) was recently proposed as a potential alternative to {sup 177}Lu (T{sub 1/2} = 6.71 days, Eβ{sup -}{sub av} = 134 keV) due to similar physical decay characteristics but additional conversion and Auger electrons that may enhance the therapeutic efficacy. The goal of this study was to compare {sup 161}Tb and {sup 177}Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). {sup 161}Tb-cm09 and {sup 177}Lu-cm09 were tested in vitro on folate receptor (FR)-positive KB and IGROV-1 cancer cells using a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) viability assay. In vivo {sup 161}Tb-cm09 and {sup 177}Lu-cm09 (10 MBq, 0.5 nmol) were investigated in two different tumour mouse models with regard to the biodistribution, the possibility for single photon emission computed tomography (SPECT) imaging and the antitumour efficacy. Potentially undesired side effects were monitored over 6 months by determination of plasma parameters and examination of kidney function with quantitative SPECT using {sup 99m}Tc-dimercaptosuccinic acid (DMSA). To obtain half-maximal inhibition of tumour cell viability a 4.5-fold (KB) and 1.7-fold (IGROV-1) lower radioactivity concentration was required for {sup 161}Tb-cm09 (IC{sub 50} ∝0.014 MBq/ml and ∝2.53 MBq/ml) compared to {sup 177}Lu-cm09 (IC{sub 50} ∝0.063 MBq/ml and ∝4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies {sup 161}Tb-cm09 reduced tumour growth more efficiently than {sup 177}Lu-cm09. These findings were in line with the higher absorbed tumour dose for {sup 161}Tb-cm09 (3.3 Gy/MBq) compared to {sup 177}Lu-cm09 (2.4 Gy/MBq). None of the monitored parameters indicated signs of impaired kidney function over the whole time period of investigation after injection of the radiofolates. Compared to {sup 177}Lu-cm09 we demonstrated equal imaging

  18. Sequential radioimmunotherapy with 177Lu- and 211At-labeled monoclonal antibody BR96 in a syngeneic rat colon carcinoma model

    DEFF Research Database (Denmark)

    Eriksson, Sophie E; Elgström, Erika; Bäck, Tom

    2014-01-01

    for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96....... Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. RESULTS: Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases...

  19. Preparation and Preliminary Biological Evaluation of {sup 177}Lu-DOTA folate as Potential Folate Receptor Targeting Therapeutic Agent

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Kang-Hyuk; Hong, Young-Don; Pyun, Mi-Sun; Lee, So-Young; Felipe, Fenelope; Yoon, Sun-Ha; Choi, Sun-Ju [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2008-10-15

    Folic Acid (FA) and FA derivatives are overexpressed on several tumor cells. The cell-membrane folic acid receptors are known to be responsible for the cellular accumulation of FA and FA analogs, such as methotrexate and folic acid. Folate has been characterized to have high affinity for the folate-receptor positive cells and tissues and considered to be useful as diagnostic imaging and therapeutic agent. In 1940s, Folate analogue, aminopterin, was first used for treatment of leukemia and recently, many folate derivatives were tried for cancer-treatment agent as well as visualization of folate receptor. Many researchers tried to conjugate folic acid with macromolecules or low molecular weight chelators through its alpha or gamma carboxylate. However, despite the reduced binding affinity, FAs are still recognized by the folate receptor. Therefore, we focused to develop folate-based radiopharmaceutical that has the potential to be used as a therapeutic agent. We report here the synthesis and the radiolabeling of {sup 177}Lu-DOTA as well as the biodistribution data of our developed compound.

  20. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2012-09-01

    3.3 – 2184.6). 3 with ECOG PS 0, 27 PS 1, 2 PS 2; 97% had bone mets, 25% extra-osseous visceral mets (2 liver, 5 lung , 1 adrenal). The majority (18 pts...blinded 177Lu-J951 versus 111In-J591 (control) with a backbone of hormonal therapy (ketoconazole and hydro- cortisone ) and will undergo planar gamma camera

  1. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with {sup 177}Lu and evaluation in vitro and in vivo stability; Radiomarcado del peptido c-DOTA-RGD y c-DOTA-RGDf con {sup 177}Lu y evaluacion de su estabilidad in vitro e in vivo

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2010-07-01

    Integrin {alpha}v{beta}3 has a critical role in tumor angio genesis and metastasis. Radiolabelled peptides based on the Arg-Gly-Asp (RGD) sequence have been reported as radiopharmaceuticals with high affinity and selectivity for the {alpha}v{beta}3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with {sup 177}Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of {sup 177}LuCl{sub 3} with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90{sup o} C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive {alpha}v{beta}3) and in athymic mice with induced MCF7 tumors. Molecular mechanics and quantum mechanics calculations were performed to explain experimental results associated with the molecular recognition. {sup 177}Lu-DOTA-RGD and {sup 177}Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to {open_square}{sub v}{open_square}{sub 3} receptors. (Author)

  2. 奥曲肽-葡聚糖-亲和素的偶联及其与177Lu-DTPA-BIS-BIOTIN的体外结合%177Lu-DTPA-BIS-BIOTIN Binding of Octreotide-dextran-avidinated PANC-1 Cell Lines in Vitro

    Institute of Scientific and Technical Information of China (English)

    邓新荣; 杜进; 翟士桢; 沈亦佳; 罗志福

    2011-01-01

    以葡聚糖为载体,奥曲肽为导向分子合成了生长抑素配体化合物奥曲肽-葡聚糖-亲和素(Tyr3-oct-reotide-dxtran 40-avidin,TOC-Dx40-Av);在体外模拟肿瘤预定位二步法以177Lu-DTPA-BIS-BIOTIN对TOC-Dx40-Av培养的PANC-1细胞的结合特性进行了研究.将长满人源胰腺癌细胞PANC-1的24孔板置于含有TOC-Dx40-Av的缓冲液中培养,2h后洗去上清液,再用含不同浓度177Lu- DTPA-BIS-BIOTIN(177Lu-DT-PA-BIS-BIOTIN的摩尔质量范围为48.8~391 pmol)的缓冲液继续培养细胞,使177Lu-DTPA-BIS-BIOTIN 与细胞上的亲和素结合,测定细胞上结合的放射性计数,考察TOC-Dx40-Av与177 Lu-DTPA-BIS-BIOTIN的结合特性以评价合成的大分子亲和素连接物的活性.实验结果显示,奥曲肽-葡聚糖-亲和素的化学纯度>99%,其中亲和素的含量为6.46 g/L.体外细胞结合实验结果表明,177Lu-DTPA-BIS-BIOTIN能快速与细胞上连接的亲和素结合,生物素与亲和素的摩尔比约为1∶1达到平衡.%Tyr3-octreotide, dextran-40 and avidin were used to prepare octreotide-dextran-avidin (TOC-Dx40-Av). DTPA-BIS-BIOTIN was labelled with 177Lu. The in vitro soma-tostatin receptor binding study was carried out by pretargeted method using TOC-Dx40-Av and 177Lu-DTPA-BIS-BIOTIN. The 24 well cell culture plates were prepared with PANC-1 cell monolayer and then incubated with TOC-Dx40-Av. After two washed with PBS, the cells were incubated with different concentration of 177 Lu-DTPA-BIS-BIOTIN (48. 8~ 391 pmol). Cells uptake was evaluated with y counter. The results showed that the chemi- cal purity of TOC-Dx40-Av was over 99%. The results also showed that TOC-Dx40-Av remained high receptor binding affinity to somatostatin receptor which indicated that TOC-Dx40-Av could bind to 177 Lu-DTPA-BIS-BIOTIN with the molar ratio of 1 ? 1 on the cell surface.

  3. Automation of labelling of Lipiodol with high-activity generator-produced 188Re.

    Science.gov (United States)

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Boucher, Eveline; Raoul, Jean-Luc; Clément, Bruno; Garin, Etienne

    2011-02-01

    This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52±2.3% and extraction yield was 98.56±1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68±9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ((188)Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07±0.9%).

  4. Automation of labelling of Lipiodol with high-activity generator-produced {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Lepareur, Nicolas, E-mail: n.lepareur@rennes.fnclcc.f [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Ardisson, Valerie [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Noiret, Nicolas [Universite Europeenne de Bretagne, Rennes (France); Ecole Nationale Superieure de Chimie de Rennes, UMR CNRS 6226, Chimie Organique et Supramoleculaire, Avenue du General Leclerc, CS 50837, 35708 Rennes Cedex 7 (France); Boucher, Eveline; Raoul, Jean-Luc [INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France); Service d' Oncologie Digestive, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); Clement, Bruno [INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Garin, Etienne [Service de Medecine Nucleaire, Centre Regional de Lutte Contre le Cancer Eugene Marquis, CS 44229, 35042 Rennes (France); INSERM U-991, Foie, Metabolismes et Cancer, 35033 Rennes (France); Universite Europeenne de Bretagne, Rennes (France)

    2011-02-15

    This work describes optimisation of the kit formulation for labelling of Lipiodol with high-activity generator-produced rhenium-188. Radiochemical purity (RCP) was 92.52{+-}2.3% and extraction yield was 98.56{+-}1.2%. The synthesis has been automated with a TADDEO module (Comecer) giving a mean final yield of 52.68{+-}9.6%, and reducing radiation burden to the radiochemist by 80%. Radiolabelled Lipiodol ({sup 188}Re-SSS/Lipiodol) is stable for at least 7 days (RCP=91.07{+-}0.9%).

  5. {sup 177}Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity {sup 111}In-octreotide

    Energy Technology Data Exchange (ETDEWEB)

    Hubble, Daniel; Kong, Grace; Michael, Michael; Johnson, Val; Ramdave, Shakher; Hicks, Rodney John [Peter MacCallum Cancer Centre, Centre for Molecular Imaging, East Melbourne, VIC (Australia)

    2010-10-15

    The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity {sup 111}In-pentetreotide can be safely treated with {sup 177}Lu-octreotate and whether addition of radiosensitising chemotherapy increases the toxicity of this agent. Records of 27 patients (aged 17-75) who received 69 (median 3 per patient) {sup 177}Lu-octreotate administrations, including 29 in conjunction with radiosensitising infusional 5-fluorouracil (5-FU) (n = 27), or capecitabine (n = 2), between October 2005 and July 2007 subsequent to 1-8 prior cycles of {sup 111}In-pentetreotide therapy were analysed. Toxicity was assessed during and at 8-12 weeks post-treatment, with further long-term assessments including survival status reviewed till death or study close-out date of 1 November 2009. Reduction in blood counts was most marked following the first dose of {sup 177}Lu-octreotate but at early follow-up the only major haematological toxicity was a single case of grade 4 lymphopaenia. Both the presence of bone metastases and the administration of chemotherapy tended to result in greater reduction in blood counts, but these differences did not reach statistical significance. On long-term follow-up, 16 patients (59%) are alive with median overall survival of 36 months (32-44 months from first {sup 177}Lu-octreotate therapy). None of the recorded deaths was directly related to treatment toxicity. One patient had late grade 4 anaemia and thrombocytopaenia secondary to bone marrow failure from progressive infiltration by tumour. No other significant long-term haematological toxicities were recorded and no leukaemia was observed. No renal toxicity was observed on serial serum creatinine or radionuclide glomerular filtration rate (GFR) determination on initial or long-term follow-up. {sup 177}Lu-octreotate is a safe and well-tolerated therapy for patients who have previously been treated with {sup 111}In-pentetreotide and can

  6. {sup 177}Lu-EDTMP for palliation of pain from bone metastases in patients with prostate and breast cancer: a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Krishan Kant; Singla, Suhas; Arora, Geetanjali; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India)

    2015-01-15

    The purpose of this study was to evaluate the efficacy and safety of {sup 177}Lu-EDTMP for pain palliation in patients with bone metastases from castration-resistant prostate and breast cancer. The secondary objective was to compare low-dose and high-dose {sup 177}Lu-EDTMP in bone pain palliation. Included in the study were 44 patients with documented breast carcinoma (12 patients; age 47 ± 13 years) or castration-resistant prostate carcinoma (32 patients; age 66 ± 9 years) and skeletal metastases. Patients were randomized into two equal groups treated with {sup 177}Lu-EDTMP intravenously at a dose of 1,295 MBq (group A) or 2,590 MBq (group B). Pain palliation was evaluated using a visual analogue score (VAS), analgesic score (AS) and Karnofsky performance score (KPS) up to 16 weeks. Toxicity was assessed in terms of haematological and renal parameters. The overall response rate (in all 44 patients) was 86 %. Complete, partial and minimal responses were seen in 6 patients (13 %), 21 patients (48 %) and 11 patients (25 %), respectively. A favourable response was seen in 27 patients (84 %) with prostate cancer and in 11 patients (92 %) with breast cancer. There was a progressive decrease in the VAS from baseline up to 4 weeks (p < 0.05). Also, AS decreased significantly from 1.8 ± 0.7 to 1.2 ± 0.9 (p < 0.0001). There was an improvement in quality of life of the patients as reflected by an increase in mean KPS from 56 ± 5 to 75 ± 7 (p < 0.0001). The overall response rate in group A was 77 % compared to 95 % in group B (p = 0.188). There was a significant decrease in VAS and AS accompanied by an increase in KPS in both groups. Nonserious haematological toxicity (grade I/II) was observed in 15 patients (34 %) and serious toxicity (grade III/IV) occurred in 10 patients (23 %). There was no statistically significant difference in haematological toxicity between the groups. {sup 177}Lu-EDTMP was found to be a safe and effective radiopharmaceutical for bone pain

  7. Biokinetic and dosimetric studies of {sup 188}Re-hyaluronic acid: a new radiopharmaceutical for treatment of hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Melendez-Alafort, Laura [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)], E-mail: laura.melendez@unipd.it; Nadali, Anna; Zangoni, Elena [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy); Banzato, Alessandra; Rondina, Maria [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Rosato, Antonio [Dipartimento di Scienze Oncologiche e Chirurgiche, Universita degli Studi di Padova, Padua (Italy); Istituto Oncologico Veneto, IOV, Padova, Padua (Italy); Mazzi, Ulderico [Dipartimento di Scienze Farmaceutiche, Universita degli Studi di Padova, 35131 Padua (Italy)

    2009-08-15

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase (ALT) levels in mice were assessed and the liver maximum tolerated dose (MTD) of {sup 188}Re-HA was determined. Results: A stable complex of {sup 188}Re-HA was obtained with high radiochemical purity (>90%) and low serum protein binding (2%). Biokinetic studies showed a rapid blood clearance (T{sub 1/2}{alpha}=21 min). Four hours after administration, {sup 188}Re-HA was almost totally removed from the blood by the liver due to the selective uptake via HA-specific receptors (73.47{+-}5.11% of the injected dose). The liver MTD in mice was {approx}40 Gy after 7.4 MBq of {sup 188}Re-HA injection. Conclusions: {sup 188}Re-HA complex showed good stability, pharmacokinetic and dosimetric characteristics that confirm its potential as a new agent for HCC radiation therapy.

  8. 188Re-labeled McAb 3H11 used as preventive for the peritoneal micrometasis of gastric cancer

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    In advancing gastric cancer,especial1y when the serous is invaded,the p1antation of cancer cells in peritoneal is common and it affectspatients' survival time severe1y. Based on successfully labeledMcAb (monoclonal antibody) 3H11 with 188Re,we investigated the effect of RIT (Radioimmuno-Therapy) with188Re-3Hll on preventing the peritoneal micrometastasis ofgastric cancer cells in nude mice toincreasethe survival time. After 1×106 BGC-823 gastriccancer cel1s were injectedinto the peritoneal cavityof each mouse, 45BABL/C nude mice weredivided into 9groups. Each group receiveddifferent doses of 188Re-3Hll or188Re-IgG, or salineI.P.16 hours postoperation.The injected volume of each mouse was 1.0mL.The resultsshowed that the survival time depended on theinjected doses during 0 to 37 MBq.Thesurvival time was l70±25.3 dafter 37 MBq 188Re-3H11 were treated.It was over 5times more than that for the saline groupand about 3 times more than that for 37MBq188-Re IgG group (p<0.05).The mice hemogramwere reduced to lowest 14 days afterinjection,but they recovered after 28 d.Conclusion: with proper injection doses,early postoperative 188Re-3H11I.P. iseffective and safe for the prevention of intra-peritoneally injectedgastric cancer cells from surviving,growing and disseminating in nude mice.

  9. Design and optimization of the production process of radiopharmaceutical {sup 177}Lu-DOTA-Nal{sup 3}-Octreotide for the treatment of gastro-entero-pancreatic tumors; Diseno y optimizacion del proceso de produccion del radiofarmaco {sup 177}Lu-DOTA-Nal{sup 3}-Octreotido para el tratamiento de tumores gastroenteropancreaticos

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez G, M. F.

    2013-07-01

    The radiolabel peptides are molecules of interest in nuclear medicine for their therapeutic and diagnostic application in cancer. Among an impressing group of relevant peptides, those similar of the somatostatin, as the Nal{sup 3}-Octreotide (NOC), have established as potential radiopharmaceuticals when presenting significant affinity for the receptors of this peptide hormone that are over expressed and broadly distributed in tumors of neuroendocrine origin, as the gastro-entero-pancreatic tumors. On the other hand, the Lutetium-177 ({sup 177}Lu) is an ideal candidate for the peptides radiolabel and has favorable characteristics to be used in radionuclide therapy. The objective of this work was designing, optimizing and to document the production process of the radiopharmaceutical {sup 177}Lu-DOTA-Nal{sup 3}-Octreotide ({sup 177}Lu-DOTANOC) for the solicitude of its sanitary registration before the Comision Federal contra Riesgos Sanitarios (COFEPRIS). For the optimization of the production process a factorial design of three variables was evaluated with mixed levels (18 combinations), where the dependent variable is the radiochemical purity and the analytic method used to determine this parameter (High Performance Liquid Chromatography) was validated. Later on, by means of the production of 3 lots of the optimized formula of the radiopharmaceutical {sup 177}Lu-DOTANOC the production process was validated and the stability long term study to determine the period of useful life was carried out. The following pharmaceutical formulation was adopted as good: 1.85 GBq (0.5μg) of {sup 177}Lu, 250 μg of DOTANOC and 150 μL of acetates Buffer 1 M ph 5 in 5 m L of the medium. The analytic method used to determine the radiochemical purity of the formulation satisfied the requirements for the wished analytic application. We can conclude that the 3 validation lots prepared under protocols of Good Production Practices, in the Plant of Radiopharmaceuticals Production of the

  10. 188Re(V)-DMSA revisited: preparation and biodistribution of a potential radiotherapeutic agent with low kidney uptake.

    Science.gov (United States)

    Dadachova, E; Chapman, J

    1998-02-01

    Methods of preparation and biodistribution in mice of tin-free 99Tcm(V)-DMSA and 188Re(V)-DMSA, a potential matching pair of radiopharmaceuticals for diagnosis and therapy of certain cancers, are described. Preparation of tin-free 188Re(V)-DMSA (I) is based on reduction with either SO2-releasing compounds like Na2S2O4 (30 mg Na2S2O4, 10 mg DMSA, 1 mg L-ascorbic acid, 37 degrees C, 60 min incubation), Na2S2O5 (as before, 70 degrees C, 15 min incubation), or HBr (0.2 ml 48% HBr, 0.2 ml 7 M HCl, 10 mg DMSA, 1 mg L-ascorbic acid, 70 degrees C, 60 min incubation). I exhibits significantly lower kidney uptake than tin-containing 188Re(V)-DMSA (II) (2-3% and 49% injected dose per gram organ, 1 h post-injection, respectively). HPLC profiles of I and II are similar. DMSA excess in tin-free 188Re(V)-DMSA is not responsible for the low kidney uptake of I. High kidney uptake of II is explained by formation of a mixed 188Re(V)-Sn-DMSA complex in vivo. Age-linked bone uptake in mice dependent on the maturation of the bone is demonstrated for both I and II.

  11. A review on the current status and production technology for {sup 188}W-{sup 188}Re generator system

    Energy Technology Data Exchange (ETDEWEB)

    Kuznetsov, R. A.; Han, H. S.; Cho, W. K.; Park, U. J.; Kim, Y. M

    1998-11-01

    The current status of {sup 188}W-{sup 188}Re generator production technology were reviewed in PART 1. Main interests were given to the aspects of {sup 188}W reactor production, irradiated targets reprocessing and generator loading technologies, such as alumina type and gel type generators. In order to develop the more convenient and advanced {sup 188}W-{sup 188}Re generator, further studies must be carried out to get the precise evaluation of production and burn-up cross section of {sup 188}W, the more easily realizable generator loading procedure, and also to optimize the column and generator design to compensate the deterioration of generator performance because of parent radionuclide decay. By irradiation of {sup 186}W enriched sample, {sup 188}W-{sup 188}Re generator production experiments were performed to evaluate the possibility of {sup 188}W-{sup 188}Re generator production using HANARO, and PART 2 describes about the experiments. The experimental results shows the possibility of practical {sup 188}W-{sup 188}Re generator production using of low-specific activity {sup 188}W produced in HANARO. (author). 79 refs., 4 tabs., 26 figs.

  12. Peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Bakker, Willem H.; Kwekkeboom, Dik J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Krenning, Eric P. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands); Herder, Wouter W. de; Aken, Maarten O. van [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2007-08-15

    Foregut carcinoid tumours have a different embryological origin than other gastroenteropancreatic neuroendocrine tumours (GEP NETs). In the total group of GEP NETs (n = 131), treatment with {sup 177}Lu-octreotate resulted in tumour remission in 47% of patients, with a median time to progression (TTP) of >36 months. As patients with foregut carcinoids may respond differently, we here present the effects of this treatment in a subgroup of patients with foregut carcinoids of bronchial, gastric or thymic origin. Nine patients with bronchial, five with gastric and two with thymic carcinoids were treated. All patients had metastasised disease. The intended cumulative dose of {sup 177}Lu-octreotate was 22.2-29.6 GBq. Southwest Oncology Group criteria were used for response evaluation. Bronchial carcinoids: Five patients had partial remission, one had minor response (MR, tumour size reduction: {>=}25%, <50%), two had stable disease (SD) and one had progressive disease (PD). Median TTP was 31 months. Gastric carcinoids: One patient had complete remission, one had MR and two had SD, including one with PD at baseline. One patient developed PD. Thymic carcinoids: One patient had SD. In the other patient, disease remained progressive. All patients: Overall remission rate was 50%, including MR. {sup 177}Lu-octreotate treatment can be effective in patients with bronchial and gastric carcinoids. Its role in thymic carcinoids cannot be determined yet because of the limited number of patients. The overall remission rate of 50% in patients with the studied foregut carcinoids is comparable to that in the total group of GEP NETs. (orig.)

  13. Multimodal Somatostatin Receptor Theranostics Using [64Cu]Cu-/[177Lu]Lu-DOTA-(Tyr3)octreotate and AN-238 in a Mouse Pheochromocytoma Model

    Science.gov (United States)

    Ullrich, Martin; Bergmann, Ralf; Peitzsch, Mirko; Zenker, Erik F.; Cartellieri, Marc; Bachmann, Michael; Ehrhart-Bornstein, Monika; Block, Norman L.; Schally, Andrew V.; Eisenhofer, Graeme; Bornstein, Stefan R.; Pietzsch, Jens; Ziegler, Christian G.

    2016-01-01

    Pheochromocytomas and extra-adrenal paragangliomas (PHEO/PGLs) are rare catecholamine-producing chromaffin cell tumors. For metastatic disease, no effective therapy is available. Overexpression of somatostatin type 2 receptors (SSTR2) in PHEO/PGLs promotes interest in applying therapies using somatostatin analogs linked to radionuclides and/or cytotoxic compounds, such as [177Lu]Lu-DOTA-(Tyr3)octreotate (DOTATATE) and AN-238. Systematic evaluation of such therapies for the treatment of PHEO/PGLs requires sophisticated animal models. In this study, the mouse pheochromocytoma (MPC)-mCherry allograft model showed high tumor densities of murine SSTR2 (mSSTR2) and high tumor uptake of [64Cu]Cu-DOTATATE. Using tumor sections, we assessed mSSTR2-specific binding of DOTATATE, AN-238, and somatostatin-14. Therapeutic studies showed substantial reduction of tumor growth and tumor-related renal monoamine excretion in tumor-bearing mice after treatment with [177Lu]Lu-DOTATATE compared to AN-238 and doxorubicin. Analyses did not show agonist-dependent receptor downregulation after single mSSTR2-targeting therapies. This study demonstrates that the MPC-mCherry model is a uniquely powerful tool for the preclinical evaluation of SSTR2-targeting theranostic applications in vivo. Our findings highlight the therapeutic potential of somatostatin analogs, especially of [177Lu]Lu-DOTATATE, for the treatment of metastatic PHEO/PGLs. Repeated treatment cycles, fractionated combinations of SSTR2-targeting radionuclide and cytotoxic therapies, and other adjuvant compounds addressing additional mechanisms may further enhance therapeutic outcome. PMID:27022413

  14. Treatment of patients with gastro-entero-pancreatic (GEP) tumours with the novel radiolabelled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Kwekkeboom, D.J.; Bakker, W.H.; Kam, B.L.; Teunissen, J.J.M.; Kooij, P.P.M.; Jong, M. de [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Herder, W.W. de; Feelders, R.A. [Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands); Eijck, C.H.J. van [Department of Surgery, Erasmus Medical Center, Rotterdam (Netherlands); Srinivasan, A.; Erion, J.L. [Mallinckrodt Medical, St. Louis, Missouri (United States); Krenning, E.P. [Department of Nuclear Medicine, Erasmus Medical Center, Dr Molewaterplein 40, 3015 GD, Rotterdam (Netherlands); Department of Internal Medicine, Erasmus Medical Center, Rotterdam (Netherlands)

    2003-03-01

    Medical treatment and chemotherapy are seldom successful in achieving objective tumour reduction in patients with metastatic neuroendocrine tumours. Treatment with the radiolabelled somatostatin analogue [{sup 90}Y-DOTA{sup 0},Tyr{sup 3}]octreotide may result in partial remissions in 10-25% of patients. The newer analogue [DOTA{sup 0},Tyr{sup 3}]octreotate (octreotate) has a ninefold higher affinity for the somatostatin receptor subtype 2 as compared with [DOTA{sup 0},Tyr{sup 3}]octreotide. Also, labelled with the beta- and gamma-emitting radionuclide {sup 177}Lu, it has proved very successful in achieving tumour regression in animal models. The effects of {sup 177}Lu-octreotate therapy were studied in 35 patients with neuroendocrine gastro-entero-pancreatic (GEP) tumours who underwent follow-up for 3-6 months after receiving their final dose. Patients were treated with doses of 100, 150 or 200 mCi {sup 177}Lu-octreotate, to a final cumulative dose of 600-800 mCi, with treatment intervals of 6-9 weeks. Nausea and vomiting within the first 24 h after administration were present in 30% and 14% of the administrations, respectively. WHO toxicity grade 3 anaemia, leucocytopenia and thrombocytopenia occurred after 0%, 1% and 1% of the administrations, respectively. Serum creatinine and creatinine clearance did not change significantly. The effects of the therapy on tumour size were evaluable in 34 patients. Three months after the final administration, complete remission was found in one patient (3%), partial remission in 12 (35%), stable disease in 14 (41%) and progressive disease in seven (21%), including three patients who died during the treatment period. Tumour response was positively correlated with a high uptake on the octreoscan, limited hepatic tumour mass and a high Karnofsky Performance Score. Because of the limited efficacy of alternative therapies, many physicians currently adopt an expectant attitude when dealing with patients with metastatic GEP tumours

  15. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with (177)Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    DEFF Research Database (Denmark)

    Wu, Yin; Pfeifer, Andreas Klaus; Myschetzky, Rebecca;

    2013-01-01

    Peptide receptor radionuclide therapy (PRRT) is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs) via somatostatin receptors. Despite promising...... clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following...

  16. The efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy in patients with neuroendocrine tumours: a meta-analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong-Jang; Pak, Kyoungjune [Pusan National University Hospital, Department of Nuclear Medicine and Biomedical Research Institute, Busan (Korea, Republic of); Koo, Phillip J.; Kwak, Jennifer J.; Chang, Samuel [University of Colorado School of Medicine, Department of Radiology, Aurora, CO (United States)

    2015-12-15

    This study was performed to evaluate the efficacy of {sup 177}Lu-labelled peptide receptor radionuclide therapy (PRRT) in patients with inoperable or metastatic neuroendocrine tumours (NETs). Systematic searches of MEDLINE and EMBASE databases were performed using the keywords of ''neuroendocrine'', ''{sup 177}Lu'' and ''prognosis''. All published studies of neuroendocrine tumours treated with {sup 177}Lu-labelled radiopharmaceuticals and evaluated with either Response Evaluation Criteria in Solid Tumours (RECIST) 1.0 or Southwest Oncology Group (SWOG) criteria or both were included. If there was more than one published study from the same institution, only one report with the information most relevant to this study was included. Each response criteria group was analysed for disease response rates and disease control rates, defined as the percentages of patients with complete response (CR) + partial response (PR), and CR + PR + stable disease (SD), respectively, to a therapeutic intervention in clinical trials of anticancer agents. The pooled proportions are presented with both a fixed-effects model and random-effects model. Six studies with 473 patients (4 in RECIST criteria group with 356 patients, 3 in SWOG criteria group with 375 patients and 1 in both groups) were included. The RECIST criteria group demonstrated disease response rates ranging between 17.6 and 43.8 % with a pooled effect of 29 % [95 % confidence interval (CI) 24-34 %]. Disease control rates ranged from 71.8 to 100 %. The random-effects model showed an average disease control rate of 81 % (95 % CI 71-91 %). The SWOG criteria group demonstrated disease response rates ranging between 7.0 and 36.5 % with a pooled effect of 23 % (95 % CI 11-38 %). Disease control rates ranged from 73.9 to 89.1 %. The random-effects model showed an average disease control rate of 82 % (95 % CI 71-91 %). {sup 177}Lu-labelled PRRT is an effective treatment

  17. β-IRRADIATION WITH A LIQUID 188Re-FILLED BALLOON PREVENTS NEOINTIMAL PROLIFERATION IN THE CAROTID OF RABBIT

    Institute of Scientific and Technical Information of China (English)

    朱建国; 崔长琮; 崔翰斌; 胡国英; 马爱群; 王东琦; 付文

    2002-01-01

    Objective To evaluate the role of β-irradiatio n with a liquid 188Re-filled balloon for limiting neointimal prolifer ation. Methods Balloon-overstretched injury was performed in the rabb it carotid artery, then β-irradiation using the liquid 188Re-filled balloon was followed immediately, and the prescribed doses was 0, 15Gy or 20Gy a t 0.5mm from the surface of vessel. All animals survived and were sacrificed at three weeks. Histopathologic analysis was performed. Results In the control group, the neointimal area was larger ( 0.40±0.04)mm2, as compared with (0.23±0.06)mm2 of the 15Gy irradiated g roup and (0.15±0.02)mm2 in the 20Gy group (P<0.05). Conclusion The β-irradiation with a liquid 188Re-f illed balloon is safe and effective.

  18. Synthesis and application of {sup 188}Re-MN-16ET/Lipiodol in a hepatocellular carcinoma animal model

    Energy Technology Data Exchange (ETDEWEB)

    Tang, I-Chang [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Luo, Tsai-Yueh, E-mail: tylo@iner.gov.tw [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Liu, Show-Wen [Chemistry Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Chan, Sun-Ho [Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 40705 (China); Kung, Hong-Chang [Department of Electronic Engineering, Tung Nan University, Taipei, Taiwan 22202 (China); Peng, Cheng-Liang [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China); Lin, Wan-Yu; Chang, Yu [Department of Nuclear Medicine, Taichung Veterans General Hospital, Taichung, Taiwan 40705 (China); Lin, Wuu-Jyh [Isotope Application Division, Institute of Nuclear Energy Research, Taoyuan, Taiwan 32546 (China)

    2011-10-15

    Introduction: Hepatocellular carcinoma is the most common form of primary hepatic carcinoma. A new N{sub 2}S{sub 2} tetradentate ligand, N-[2-(triphenylmethyl)thioethyl]-3-aza-19-ethyloxycarbonyl-3- [2-(triphenylmethyl)thioethyl]octadecanoate (H{sub 3}MN-16ET), was introduced and labeled with {sup 188}Re to create {sup 188}Re-MN-16ET in the Lipiodol phase. The potential of {sup 188}Re-MN-16ET/Lipiodol for hepatoma therapy was evaluated in a hepatocellular carcinoma animal model of Sprague-Dawley rats implanted with the N1S1 cell line. Methods: Synthesis of H{sub 3}MN-16ET was described, and characterization was identified by infrared, nuclear magnetic resonance and mass spectra. We compared the effects of transchelating agents (glucoheptonate or tartaric acid) and a reducing agent (stannous chloride) on the complexing of {sup 188}Re-perrhenate and H{sub 3}MN-16ET. Twenty-four rats implanted with hepatoma were injected with 3.7 MBq/0.1 ml of {sup 188}Re-MN-16ET/Lipiodol or {sup 188}Re-MN-16ET via transcatheter arterial embolization. Biodistribution experiments and single-photon emission computed tomography imaging were performed to investigate tumor accumulation. Results: H{sub 3}MN-16ET was proved to easily conjugate with the Re isotope and showed good solubility in Lipiodol. The radiochemical purity of {sup 188}Re-MN-16ET/Lipiodol with 10 mg tartaric acid and stannous chloride was shown to be more than 90%. The major distribution sites of {sup 188}Re-MN-16ET in Sprague-Dawley rats were hepatoma and the liver. However, the radioactivity at the tumor site postadministered with {sup 188}Re-MN-16ET was quickly decreased from 9.15{+-}0.23 (at 1 h) to 2.71%{+-}0.18% of injected dose/g (at 48 h). The biodistribution and micro-single-photon emission computed tomography/computed tomography image data showed that {sup 188}Re-MN-16ET/Lipiodol was selectively retained at the tumor site, with 11.55{+-}1.44, 13.16{+-}1.46 and 10.67%{+-}0.95% of injected dose/g at 1, 24 and 48 h

  19. Lipiodol solution of a lipophilic agent, {sup 188}Re-TDD, for the treatment of liver cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Jae Min E-mail: jmjng@snu.ac.kr; Kim, Young Joo; Lee, Yoon Sang; Ko, Jun Il; Son, Miwon; Lee, Dong Soo; Chung, June-Key; Park, Jae Hyung; Lee, Myung Chul

    2001-02-01

    Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of {sup 188}Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of {sup 188}Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of {sup 188}Re-TDD is a promising agent for liver cancer therapy.

  20. Evaluating the potential of {sup 188}Re-SOCTA-trastuzumab as a new radioimmunoagent for breast cancer treatment

    Energy Technology Data Exchange (ETDEWEB)

    Luo, T.-Y. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China)], E-mail: tylo@iner.gov.tw; Tang, I-C.; Wu, Y.-L.; Hsu, K.-L. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China); Liu, S.-W. [Chemistry Division, Institute of Nuclear Energy Research, Taoyuan 325, Taiwan (China); Kung, H.-C. [Department of Electrical Engineering, Tung Nan University, Taipei 222, Taiwan (China); Lai, P.-S. [Department of Chemistry, National Chung Hsing University, Taichung 402, Taiwan (China); Lin, W.-J. [Isotope Application Division, Institute of Nuclear Energy Research, P.O. Box 3-27, Longtan, Taoyuan 325, Taiwan (China)

    2009-01-15

    Introduction: Radioimmunotherapy, which utilizes monoclonal antibodies and therapeutic radioisotopes against antigen-expressing tumor tissues, is an attractive therapeutic approach for cancer therapy. Trastuzumab (Herceptin) is a humanized anti-HER-2/neu monoclonal antibody for breast cancer treatment. In this paper, we introduce a new radioimmunoagent, {sup 188}Re-trastuzumab, via a bifunctional ligand, succinimidyl 3,6-diaza-5-oxo-3-[2-((triphenylmethyl)thio)ethyl] -8-[(triphenylmethyl)thio]octanoate (SOCTA), and evaluate its potential to be a therapeutic radiopharmaceutical for breast cancer treatment. Methods: Equimolar amounts of SOCTA and trastuzumab were selected to react, and the conjugation ratio of SOCTA-trastuzumab was evaluated by the MALDI-TOF method. The immunoreactivity of SOCTA-trastuzumab was compared with nonconjugated trastuzumab in HER-2/neu overexpressing human breast cancer cell BT-474. Biodistribution experiment and microSPECT/CT images of {sup 188}Re-SOCTA-trastuzumab being administered intravenously to SCID mice bearing xenografted BT-474 breast cancer were investigated to evaluate the tumor-targeting capability. Results: The covalent attachment of SOCTA to trastuzumab (at 1:1 molar ratio) resulted in the averaged conjugation ratio of 0.27{+-}0.06 (n=3). The complex could easily be labeled with {sup 188}Re and achieve 95% radiochemical purity (RCP) after 1 h of reaction at room temperature. The in vitro stability study also revealed that the RCP of {sup 188}Re-SOCTA-trastuzumab was at a value of more than 85% after 48 h of incubation with human serum. The immunoreactivity evaluation showed that SOCTA-trastuzumab and nonconjugated trastuzumab had similar binding capacity (B{sub max}) to HER-2/neu receptor in BT-474 cells. The animal experiments showed that {sup 188}Re-SOCTA-trastuzumab accumulated more intensively in the tumor site as compared to normal tissue. Conclusion: We suggest that {sup 188}Re-SOCTA-trastuzumab could be a potential

  1. Comparative study of 188Re( V )-DMSA and 99mTc ( V )-DMSA in tumor model%188Re(V)-DMSA与99mTc(V)-DMSA在肿瘤模型体内的对比研究

    Institute of Scientific and Technical Information of China (English)

    孙逊; 安锐

    2004-01-01

    Objective To compare the biodistribution and imaging characteristics of 188Re(V)-DMSA and 99mTc(V)-DMSA in tumor model, and to discuss the possibility of treating tumors with 188Re(V)-DMSA. Methods The solid neoplasm bearing mice (Ehrlich carcinoma bearing mice) models underwent biodistribution study and static whole body planar imaging after injection of 188Re(V)-DMSA and 99mTc(V)-DMSA respectively. When the mice were sacrificed at different time after the injection, the tumor, blood and contralateral normai muscles were removed, weighted and the radioactivity was measured. Then the radioactivity ratios of target (tumor)-to-blood (T/B),target-to-non targeted (contralateral limbs or muscles) (T/NT) were calculated. ROIs were drawn and T/NT were calculated in planar imagines. Results Two radiopharmaceuticals were mainly concentrated in bone and kidney, and the uptake ratios in tumor were high too.The half-clearance times of these two radiopharmaceuticals in blood were both less than 1h. The greatest T/NT ratio of 99mTc group was higher than 188Re group in planar imagings, but the highest T/B, T/NT ratios of these two radiopharmaceuticals in biodistribution study had no significant difference and were all above 3.0. Conclusion The biodistribution characteristics of 188Re(V)-DMSA and 99mTc( V)-DMSA were similar. 188Re(V)-DMSA has good applied foreground in treating tumors and their metastases.%目的比较188Re(V)-DMSA(五价188Re-二巯基丁二酸钠)和99mTc(V)-DMSA在肿瘤模型体内生物分布与显像的特点,探讨188Re(V)-DMSA用于肿瘤治疗的可能性.方法用188Re(V)-DMSA和99mTc(V)-DMSA对实验性实体肿瘤(小鼠艾氏腹水癌)模型进行生物学分布实验和全身平面显像,并通过脏器克组织百分摄取率(%ID/g)测定法和感兴趣区(ROI)技术进行定量分析,计算各时点两种放射性药物的靶/血、靶/非靶比值.结果两种放射性药物均主要浓聚于骨骼和肾脏,肿瘤组织也有较高的摄

  2. Synthesis, analysis, purification and biodistribution in an animal model of radiopharmaceutical {sup 177}Lu{sup 3+} -dotatato for diagnostic and therapeutic use in neuroendocrine tumors; Sintese, analise, purificacao e biodistribuicao em modelo animal do radiofarmaco {sup 177}Lu{sup 3+} -dotatato para uso diagnostico e terapeutico em tumores neuroendocrinos

    Energy Technology Data Exchange (ETDEWEB)

    Caldeira Filho, Jose de Souza

    2009-07-01

    The aim of this work was to propose rationalization in the synthesis, analysis and purification of radiopharmaceutical {sup 177} Lu{sup 3+} - DOTATATO for diagnostic and therapeutic use in neuroendocrine tumors, as well as for evaluation g biodistribution of this radiopharmaceutical an animal-mode. The complexation reaction for the synthesis of radiopharmaceutical was carried out in ammonium acetate buffer 0.5 M, p H 7.0, for 30 minutes at 95 deg C. The radiochemical purity was > 95%, according to analysis by chromatography in ITLC-SG, when using the sodium citrate buffer 0,1 M, p H 5.0, as the mobile phase. The molar-limit ratio {sup 177}Lu{sup 3+}:DOTATATO, in ammonium acetate buffer 0.5 M, p H 7.0, for 30 minutes at 95 deg C, was dependent on the specific activity and origin of the radioisotope, this being 1:3.5 (370 MBq : 26{mu}g) for that from the Oak Ridge National Laboratory /USA, and 1:16 (370 MBq: 11.8 {mu}g) for that from Nuclear Analytical and Medical Services/Holland, when considering a decay of five days from the production date of te radioisotopes. This rationalization in the synthesis of radiopharmaceutical {sup 177}Lu{sup 3+} - DOTATATO permits high economy in production costs. Chemical studies on the synthesis of radiopharmaceuticals also placed in evidence the interference of {sup 177}Hf{sup 4+}, the decay product of {sup 177}Lu{sup 3=}, as the {sup 177} Lu{sup 3=} competitor for DOTATATO. Radiopharmaceutical preparation proved to be stable during 24 hours, at an activity rate of 2775 MBq, with the addition of 0.6 mg/mL of gentisic acid and when kept in dry ice. In biodistribution studies on Swiss and Nuce mice, the specificity of radiopharmaceutical for somatostatin positive-receptor tissues, such as the pancreas, stomach, lungs, adrenal glands, kidneys and the cell tumor AR42J was demonstrated. (author)

  3. Individualized dosimetry in patients undergoing therapy with {sup 177}Lu-DOTA-D-Phe{sup 1}-Tyr{sup 3}-octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Sandstroem, Mattias [Uppsala University Hospital, Department of Oncology, Radiology and Clinical Immunology, Division of Medical Physics, Uppsala (Sweden); Uppsala University Hospital, Department of Hospital Physics, Uppsala (Sweden); Garske, Ulrike [Uppsala University Hospital, Department of Medical Sciences, Division of Nuclear Medicine, Uppsala (Sweden); Granberg, Dan [Uppsala University Hospital, Department of Medical Sciences, Division of Endocrine Oncology, Uppsala (Sweden); Sundin, Anders [Karolinska University Hospital, Department of Molecular Medicine and Surgery, Division of Diagnostic Radiology, Stockholm (Sweden); Lundqvist, Hans [Uppsala University, Department of Oncology, Radiology and Clinical Immunology, Rudbeck Laboratory, Uppsala (Sweden)

    2010-02-15

    In recent years, targeted radionuclide therapy with [{sup 177}Lu-DOTA{sup 0}, Tyr{sup 3}]octreotate for neuroendocrine tumours has yielded promising results. This therapy may be further improved by using individualized dosimetry allowing optimization of the absorbed dose to the tumours and the normal organs. The aim of this study was to investigate the feasibility and reliability of individualized dosimetry based on SPECT in comparison to conventional planar imaging. Attenuation-corrected SPECT data were analysed both by using organ-based volumes of interest (VOIs) to obtain the total radioactivity in the organ, and by using small VOIs to measure the tissue radioactivity concentration. During the first treatment session in 24 patients, imaging was performed 1, 24, 96 and 168 h after [{sup 177}Lu-DOTA{sup 0}, Tyr{sup 3}]octreotate infusion. Absorbed doses in non tumour-affected kidney, liver and spleen were calculated and compared for all three methods (planar imaging, SPECT organ VOIs, SPECT small VOIs). Planar and SPECT dosimetry were comparable in areas free of tumours, but due to overlap the planar dosimetry highly overestimated the absorbed dose in organs with tumours. Furthermore, SPECT dosimetry based on small VOIs proved to be more reliable than whole-organ dosimetry. We conclude that SPECT dosimetry based on small VOIs is feasible and more accurate than conventional planar dosimetry, and thus may contribute towards optimising targeted radionuclide therapy. (orig.)

  4. Development of {sup 177}Lu-DTPA-SPIO conjugates for potential use as a dual contrast SPECT/MRI imaging agent

    Energy Technology Data Exchange (ETDEWEB)

    Shanehsazzadeh, Saeed; Yousefnia, Hassan [Nuclear Science and Technology Research Institute (NSTRI), Tehran (Iran, Islamic Republic of); Gruettner, Cordula [Micromod Partikeltechnologie GmbH, Rostock (Germany); and others

    2016-08-01

    This study describes the preparation, biodistribution of {sup 177}Lu-DTPA-SPIO after intravenous injection in rats. The chelator DTPA dianhydride was conjugated to SPIO NPs using a small modification of the well-known cyclic anhydride method. Conjugation was done at a 1:2 (SPIO:ccDTPA) molar ratio. Conjugation reaction was purified with Magnetic assorting column (MACs) using high gradient magnetic field following incubation, the radio labeled conjugate was checked using RTLC method for labeling and purity checked. The RTLC showed that labeling yield was above 99% after purification and the compound have good in-vitro stabilities until 48 h post injection in the presence of human serum. The biodistribution of {sup 177}Lu-DTPA-SPIO in rats showed dramatic uptake in the reticuloendothelial system (RES) and their clearance is so fast in other organs especially in the blood. In conclusion, due to high uptakes of this radiotracer in the liver and spleen and their fast clearance from other tissues, especially in blood, it is suggested that this radiotracer would be suitable for RES studies.

  5. Synthesis and evaluation of Lys{sup 1}(α, γ-Folate)Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin(1-14) as a potential theranostic radiopharmaceutical for breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Aranda L, L.; Ferro F, G.; Azorin V, E.; Ramirez, F. M.; Ocampo G, B.; Santos C, C.; Jimenez M, N. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Issac O, K. [Universidad Autonoma del Estado de Mexico, Facultad de Medicina, 50180 Toluca, Estado de Mexico (Mexico)

    2015-10-15

    Full text: Lutetium-177 labeled hetero bivalent molecules that interact with different targets on tumor cells have been proposed as a new class of theranostic radiopharmaceuticals. The aim of this work was to synthesize Lys{sup 1} (α,γ-Folate)-Lys{sup 3}({sup 177}Lu-DOTA)-Bombesin (1-14) ({sup 177}LuFolate-Bn), as well as to assess its in vitro and in vivo potential for molecular imaging and targeted radiotherapy of breast tumors expressing folate receptors (Fr) and gastrin releasing peptide receptors (GRPR). Lys{sup 1} Lys{sup 3} (DOTA)-Bombesin (1-14) was conjugated to the terminal carboxylic group of the folic acid and the product purified by size-exclusion HPLC. Chemical characterization was carried out by UV-vis, Ft-IR spectroscopies and MALDI-TOF mass spectrometry. {sup 177}Lu labeling was performed by reaction of {sup 177}LuCl{sub 3} with the Lys{sup 1} (α,γ-Folate)-Lys{sup 3} (DOTA)-Bombesin (Folate-Bn) conjugate. In vitro binding studies were carried out in T47D breast cancer cells (positive to Fr and GRPR). Biokinetic studies and micro-SPECT/CT images were obtained using athymic mice with T47D induced tumors. Spectroscopic studies and HPLC analyses indicated that the conjugate was obtained with high chemical and radiochemical purity (98 ± 1.3%). T47D-tumors were clearly visible with high contrast at 2 h after radiopharmaceutical administration. The {sup 177}Lu-absorbed dose delivered to tumors was 23.9 ± 2.1 Gy (74 MBq, intravenously administered) {sup 177}Lu-Folate-Bn demonstrated properties suitable as a theranostic radiopharmaceutical for breast tumors expressing Fr s and GRPR s. (Author)

  6. Nuclear model calculations on cyclotron production of {sup 51}Cr

    Energy Technology Data Exchange (ETDEWEB)

    Kakavand, Tayeb [Imam Khomeini International Univ., Qazvin (Iran, Islamic Republic of). Dept. of Physics; Aboudzadeh, Mohammadreza [Nuclear Science and Technology Research Institute/AEOI, Karaj (Iran, Islamic Republic of). Agricultural, Medical and Industrial Research School; Farahani, Zahra; Eslami, Mohammad [Zanjan Univ. (Iran, Islamic Republic of). Dept. of Physics

    2015-12-15

    {sup 51}Cr (T{sub 1/2} = 27.7 d), which decays via electron capture (100 %) with 320 keV gamma emission (9.8 %), is a radionuclide with still a large application in biological studies. In this work, ALICE/ASH and TALYS nuclear model codes along with some adjustments are used to calculate the excitation functions for proton, deuteron, α-particle and neutron induced on various targets leading to the production of {sup 51}Cr radioisotope. The production yields of {sup 51}Cr from various reactions are determined using the excitation function calculations and stopping power data. The results are compared with corresponding experimental data and discussed from point of view of feasibility.

  7. {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    Energy Technology Data Exchange (ETDEWEB)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar [All India Institute of Medical Sciences, Department of Nuclear Medicine, Ansari Nagar, New Delhi (India); Sahoo, Ranjit Kumar [All India Institute of Medical Sciences, Department of Medical Oncology, BR Ambedkar Rotary Cancer Hospital, New Delhi (India); Seth, Amlesh [All India Institute of Medical Sciences, Department of Urology, New Delhi (India)

    2017-01-15

    The purpose of this study was to evaluate the efficacy and safety of a novel theranostic agent, {sup 177}Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer (mCRPC). Thirty-one mCRPC patients with progressive disease despite second-line hormonal therapy and/or docetaxel chemotherapy were recruited for the study. All patients underwent diagnostic{sup 68}Ga-PSMA-HBED-CCPET/CT, prior to inclusion for therapy. Included patients then underwent quarterly {sup 177}Lu-DKFZ-PSMA-617 therapy. Hematological, kidney function, liver function tests, and serum PSA levels were recorded before and after therapy at 2 weeks, 4 weeks, and 3 month intervals. Biochemical response was assessed with trend in serum PSA levels. Metabolic response was assessed by PERCIST 1 criteria. Clinical response was assessed by visual analogue score (VASmax) analgesic score (AS), Karanofsky performance status (KPS), and toxicity and response criteria of the Eastern Cooperative Oncology Group (ECOG) criteria. The mean age of patients was 65.93 ± 9.77 years (range: 38-81 years). The mean activity administered in the 31 patients was 5069 ± 1845 MBq ranging from one to four cycles. There was a decline in the mean serum PSA levels from the baseline (baseline: 275 ng/mL, post 1st cycle therapy: 141.75 ng/mL). Based on biochemical response criteria 2/31, 20/31, 3/31, and 6/31 had complete response (CR), partial response(PR), stable disease (SD), and progressive disease (PD), respectively. Metabolic response revealed 2/6 patients with CR, and the remaining 3/6 patients with PR and 1/6 patients with SD. The mean VASmax score decreased from 7.5 to 3. The mean analgesic score decreased from 2.5 to 1.8 after therapy. The mean KPS score improved from 50.32 to 65.42 after therapies. The mean ECOG performance status improved from 2.54 to 1.78 after therapy. Two patients experienced grade I and grade II hemoglobin toxicity each. None of the patients experienced nephrotoxicity or hepatotoxicity

  8. Development of methods of labeling pentavalent DMSA with {sup 99m}Tc and {sup 188}Re; Desenvolvimento de metodos para marcacao de DMSA pentavalente com {sup 99m}Tc e {sup 188}Re

    Energy Technology Data Exchange (ETDEWEB)

    Brambilla, Tania de Paula, email: jtoniolo@ipen.br

    2009-07-01

    Technetium-99 m is the most useful radionuclide in diagnostic imaging procedures in Nuclear Medicine, more than 80 percent of radiopharmaceuticals are {sup 99m}Tc-labeled compounds. {sup 99m}Tc-DMSA(V) has been used for imaging of soft tissue, head and neck tumors. It shows a particularly high specificity for medullary thyroid carcinoma and bone metastases in a variety of cancers. Biodistribution studies of {sup 188}Re-DMSA(V) have shown that its general pharmacokinetic properties are similar to that of {sup 99m}Tc-DMSA(V), so this agent could be used for targeted radiotherapy of these tumors. The aim of this work is the development of methods of labeling DMSA(V) with {sup 99m}Tc and {sup 188}Re. {sup 99m}Tc-DMSA(V) can be prepared by two methods. One of them is the indirect one, through the use of a commercial kit of DMSA (III), by adjusting the pH from 2.5 to {approx} 8.5 with NaHCO{sub 3}. This method was evaluated and optimized presenting high labeling yields. The other method is the direct one, through the preparation of a lyophilised kit ready for labeling with {sup 99m}Tc, being the method of interest of this work, due to the easy of its clinical use. The most adequate formulation of the kit was: 1.71 mg of DMSA, 0.53 mg of SnCl{sub 2}.2H{sub 2}O and 0.83 mg of ascorbic acid (pH 9). Labeling yields higher than 95% were achieved labeling this kit with 1 to 2 m L of {sup 99m}Tc with activities up to 4736 MBq (128 mCi). The kit was stable up to 6 months and biodistribution studies confirmed the quality of the DMSA (V) labeled with {sup 99m}Tc using this kit. The reduction potential of Re is lower than the one for Tc, so the labeling conditions of {sup 188}Re-DMSA(V) are different from the ones used for {sup 99m}Tc- DMSA(V). {sup 188}Re-DMSA(V) is prepared in acid solution, that makes it possible to use the DMSA (III) commercial kit developed for labeling with {sup 99m}Tc, prepared in pH 2.5, for labeling with {sup 188}Re. Labeling yields higher than 95% were

  9. Induction of Anti-Tumor Immune Responses by Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE in a Murine Model of a Human Neuroendocrine Tumor

    Directory of Open Access Journals (Sweden)

    Michael Bzorek

    2013-10-01

    Full Text Available Peptide receptor radionuclide therapy (PRRT is a relatively new mode of internally targeted radiotherapy currently in clinical trials. In PRRT, ionizing radioisotopes conjugated to somatostatin analogues are targeted to neuroendocrine tumors (NETs via somatostatin receptors. Despite promising clinical results, very little is known about the mechanism of tumor control. By using NCI-H727 cells in an in vivo murine xenograft model of human NETs, we showed that 177Lu-DOTATATE PRRT led to increased infiltration of CD86+ antigen presenting cells into tumor tissue. We also found that following treatment with PRRT, there was significantly increased tumor infiltration by CD49b+/FasL+ NK cells potentially capable of tumor killing. Further investigation into the immunomodulatory effects of PRRT will be essential in improving treatment efficacy.

  10. Efficiency of the metabolic radiotherapy with {sup 177}Lu Octreotate in the case of gastric endocrine tumor with hepatic metastases; Efficacite de la radiotherapie metabolique au{sup 177}Lu Octreotate dans le cas d'une tumeur endocrine gastrique avec metastases hepatiques

    Energy Technology Data Exchange (ETDEWEB)

    Leghzali Moise, H.; Besse, H.; Stievenart, J.L [Medecine nucleaire, hopital Beaujon, AP-HP, (France); Scigliano, S. [service hospitalier Frederic-Joliot, Orsay, (France); Mortazavi Jehannod, N.; Lebtahid, R.; Le Guludec, D. [medecine nucleaire, hopital Bichat, AP-HP, (France); Ruszniewski, P. [pancreato-gastroenterologie, hopital Beaujon, AP-HP, (France)

    2009-05-15

    The therapy means of evolved, metastases or inoperable forms of digestive endocrine tumors are limited. we illustrate a case of treatment efficiency by {sup 177}Lu-Octreotate of a well differentiated gastric endocrine tumor with hepatic metastases. conclusions: the metabolic radiotherapy of endocrine tumors constitute a new alternative of conventional treatments, showing the achievement of objective tumor responses at advanced stages, and in failure of conventional treatments. it is necessary to identify the predictive factors of the therapy response in order to optimize the results and to limit the toxicity. (N.C.)

  11. Evaluation of the cell death mechanisms activated by the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy; Evaluacion de los mecanismos de muerte celular activados por el radiofarmaco {sup 177}Lu-DOTA-anti-CD20 en un intervalo de dosis de 1 a 5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G., E-mail: erica.azorin@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2016-10-15

    The radio immunotherapy with anti-CD20 antibodies significantly increases the remission rate of patients with B-cell lymphomas over expressing the CD20. The radiolabeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. The anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The {sup 177}Lu is a beta particle emitter (max. 0.497 MeV) with a maximum reach on soft tissue of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45 m Ci/m{sup 2}) for {sup 177}Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of action by synergistic effect of anti-CD20 and radionuclide have not been studied. In this work was evaluated; by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with {sup 177}Lu-DOTA-Anti-CD20 in non-Hodgkin (Raji) lymphoma cells. The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20, are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation, activation of repair mechanisms and increased radio sensitivity) causes the acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation

  12. Uptake of the {sup 188}Re(V)-DMSA complex by cervical carcinoma cells in nude mice: pharmacokinetics and dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Salinas, Laura; Ferro-Flores, Guillermina E-mail: gff@nuclear.inin.mxtendilla@acnet.net; Arteaga-Murphy, Consuelo; Pedraza-Lopez, Martha; Hernandez-Gutierrez, Salomon; Azorin-Nieto, Juan

    2001-03-01

    The uptake of the rhenium-188 ({sup 188}Re(V)-DMSA) complex of dimercaptosuccinic acid by cervical carcinoma cells in nude mice was evaluated. The pharmacokinetics and dosimetry calculations in normal rats were also evaluated. The images obtained in mice did not show significant accumulation in metabolic organs and the biodistribution studies showed that 3.52{+-}0.76% of the injected activity per gram (n=4) was taken up by the tumor. This percentage produces a cumulated activity of 35.63{+-}8.40 MBq h and an equivalent dose per injected activity of 260{+-}8.91 mSv/MBq. Pharmacokinetics and dosimetry of the {sup 188}Re(V)-DMSA complex indicate that this radiopharmaceutical could be evaluated in patients with soft tissue tumors, since the risk of radiation damage to the kidney or red bone marrow could not be an obstacle for its application in therapeutic nuclear medicine.

  13. Radiolabeling of rituximab with {sup 188}Re and {sup 99m}Tc using the tricarbonyl technology

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla Roberta [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Jeger, Simone [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Osso, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares, Av. Professor Lineu Prestes 2242, 05508-000 Sao Paulo (Brazil); Mueller, Cristina; De Pasquale, Christine; Hohn, Alexander; Waibel, Robert [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Schibli, Roger, E-mail: roger.schibli@psi.c [Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Paul Scherrer Institute, 5232 Villigen-PSI (Switzerland); Department of Chemistry and Applied Biosciences of the ETH, 8093 Zurich (Switzerland)

    2011-01-15

    Introduction: The most successful clinical studies of immunotherapy in patients with non-Hodgkin's lymphoma (NHL) use the antibody rituximab (RTX) targeting CD20{sup +} B-cell tumors. Rituximab radiolabeled with {beta}{sup -} emitters could potentiate the therapeutic efficacy of the antibody by virtue of the particle radiation. Here, we report on a direct radiolabeling approach of rituximab with the {sup 99m}Tc- and {sup 188}Re-tricarbonyl core (IsoLink technology). Methods: The native format of the antibody (RTX{sub wt}) as well as a reduced form (RTX{sub red}) was labeled with {sup 99m}Tc/{sup 188}Re(CO){sub 3}. The partial reduction of the disulfide bonds to produce free sulfhydryl groups (-SH) was achieved with 2-mercaptoethanol. Radiolabeling efficiency, in vitro human plasma stability as well as transchelation toward cysteine and histidine was investigated. The immunoreactivity and binding affinity were determined on Ramos and/or Raji cells expressing CD20. Biodistribution was performed in mice bearing subcutaneous Ramos lymphoma xenografts. Results: The radiolabeling efficiency and kinetics of RTX{sub red} were superior to that of RTX{sub wt} ({sup 99m}Tc: 98% after 3 h for RTX{sub red} vs. 70% after 24 h for RTX{sub wt}). {sup 99m}Tc(CO){sub 3}-RTX{sub red} was used without purification for in vitro and in vivo studies whereas {sup 188}Re(CO){sub 3}-RTX{sub red} was purified to eliminate free {sup 188}Re-precursor. Both radioimmunoconjugates were stable in human plasma for 24 h at 37{sup o}C. In contrast, displacement experiments with excess cysteine/histidine showed significant transchelation in the case of {sup 99m}Tc(CO){sub 3}-RTX{sub red} but not with pre-purified {sup 188}Re(CO){sub 3}-RTX{sub red}. Both conjugates revealed high binding affinity to the CD20 antigen (K{sub d}=5-6 nM). Tumor uptake of {sup 188}Re(CO){sub 3}-RTX{sub red} was 2.5 %ID/g and 0.8 %ID/g for {sup 99m}Tc(CO){sub 3}-RTX{sub red} 48 h after injection. The values for other

  14. Reduction of β-radiation exposure during preparation of 188Re-labelled Lipiodol for hepatocellular carcinoma treatment.

    Science.gov (United States)

    Lepareur, Nicolas; Laffont, Sophie; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-02-01

    Rhenium-188 (188Re) is of widespread interest for treating various diseases because of its attractive physical and chemical properties. The routine preparation of therapeutic doses of 188Re-labelled tracers can result in significant radiation exposure to the operator. We studied the impact of automating the preparation of 188Re-Lipiodol on the radiochemist's exposure, as well as the importance of the model of syringe shielding. To monitor radiation exposure continuously readable electronic personal dosimeters were used. Thermoluminescence dosimeters were fixed to the probable most exposed fingers of the radiochemist during preparation of the radiotracer and during the syringing. Dose rates were measured using a Babyline. Automation of the synthesis reduced personal dose equivalents from 2.60±4.35 to 1.61±1.20 µSv/GBq [Hp(10)] and from 38.37±55.28 to 21.84±16.14 µSv/GBq [Hp(0.07)]. Dose to the extremities was also reduced (-80% for the right hand; -58% for the left one). The Lemer-Pax PSWG syringe shield led to a slightly lower dose to the hands compared with the Medisystem (1.1±0.27 vs. 1.34±0.6 mSv/GBq for the right finger). Automation of the synthesis leads to a significant decrease in radiation exposure to the operator. The Lemer-Pax PSWG syringe shield provides better hand protection than the smaller Medisystem Mediclic.

  15. Rhenium-188 Production in Hospitals, by W-188/Re-188 Generator, for Easy Use in Radionuclide Therapy

    Directory of Open Access Journals (Sweden)

    Maria Argyrou

    2013-01-01

    Full Text Available Rhenium-188 (Re-188 is a high energy -emitting radioisotope obtained from the tungsten-188/rhenium-188 (W-188/Re-188 generator, which has shown utility for a variety of therapeutic applications in nuclear medicine, oncology, and interventional radiology/cardiology. Re-188 decay is accompanied by a 155 keV predominant energy -emission, which could be detected by -cameras, for imaging, biodistribution, or absorbed radiation dose studies. Its attractive physical properties and its potential low cost associated with a long-lived parent make it an interesting option for clinical use. The setup and daily use of W-188/Re-188 generator in hospital nuclear medicine departments are discussed in detail. The clinical efficacy, for several therapeutic applications, of a variety of Re-188-labeled agents is demonstrated. The high energy of the -emission of Re-188 is particularly well suited for effective penetration in solid tumours. Its total radiation dose delivered to tissues is comparable to other radionuclides used in therapy. Furthermore, radiation safety and shielding requirements are an important subject of matter. In the case of bone metastases treatment, therapeutic ratios are presented in order to describe the efficacy of Re-188 usage.

  16. Specific efficacy of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced neuroendocrine tumours of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sabet, Amir; Dautzenberg, Kristina; Haslerud, Torjan; Aouf, Anas; Sabet, Amin; Biersack, Hans-Juergen [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Simon, Birgit [University Hospital, Department of Radiology, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Ezziddin, Samer [University Hospital, Department of Nuclear Medicine, Bonn (Germany); Saarland University, Department of Nuclear Medicine, Homburg (Germany)

    2015-07-15

    Increasing evidence supports the value of peptide receptor radionuclide therapy (PRRT) in patients with metastatic neuroendocrine tumours (NET), but there are limited data on its specific efficacy in NET of small intestinal (midgut) origin. This study aims to define the benefit of PRRT with {sup 177}Lu-octreotate for this circumscribed entity derived by a uniformly treated patient cohort. A total of 61 consecutive patients with unresectable, advanced small intestinal NET G1-2 stage IV treated with {sup 177}Lu-octreotate (4 intended cycles at 3-month intervals, mean activity per cycle 7.9 GBq) were analysed. Sufficient tumour uptake on baseline receptor imaging and either documented tumour progression (n = 46) or uncontrolled symptoms (n = 15) were prerequisites for treatment. Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Assessment of survival was performed using Kaplan-Meier curves and Cox proportional hazards model for uni- and multivariate analyses. Toxicity was assessed according to standardized follow-up laboratory work-up including blood counts, liver and renal function, supplemented with serial {sup 99m}Tc-diethylenetriaminepentaacetic acid (DTPA) clearance measurements. The median follow-up period was 62 months. Reversible haematotoxicity (≥ grade 3) occurred in five patients (8.2 %). No significant nephrotoxicity (≥ grade 3) was observed. Treatment response according to modified SWOG criteria consisted of partial response in 8 (13.1 %), minor response in 19 (31.1 %), stable disease in 29 (47.5 %) and progressive disease in 5 (8.2 %) patients. The disease control rate was 91.8 %. Median progression-free survival (PFS) and overall survival (OS) was 33 [95 % confidence interval (CI) 25-41] and 61 months (95 % CI NA), respectively. Objective response was associated with longer survival (p = 0.005). Independent predictors of shorter PFS were

  17. Bone marrow dosimetry in peptide receptor radionuclide therapy with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Forrer, Flavio; Krenning, Eric P.; Kooij, Peter P.; Bernard, Bert F.; Bakker, Willem H.; Teunissen, Jaap J.M.; Jong, Marion de; Kwekkeboom, Dik J. [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Konijnenberg, Mark [Mallinckrodt Medical BV, Research and Development, Petten (Netherlands); Lom, Kirsten van [Erasmus MC Rotterdam, Department of Haematology, Rotterdam (Netherlands); Herder, Wouter W. de [Erasmus MC Rotterdam, Department of Internal Medicine, Rotterdam (Netherlands)

    2009-07-15

    Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called ''remainder of the body'' to the bone marrow. Bone marrow aspirates were drawn in 15 patients after treatment with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. (1) After PRRT with [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone

  18. Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model

    Directory of Open Access Journals (Sweden)

    Huang FYJ

    2015-01-01

    Full Text Available Feng-Yun J Huang,1 Te-Wei Lee,2 Chih-Hsien Chang,2 Liang-Cheng Chen,2 Wei-Hsin Hsu,2 Chien-Wen Chang,1 Jem-Mau Lo1 1Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan; 2Institute of Nuclear Energy Research, Longtan, Taiwan Purpose: In this study, the 188Re-labeled PEGylated nanoliposome (188Re-liposome was prepared and evaluated as a therapeutic agent for glioma.Materials and methods: The reporter cell line, F98luc was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of 188Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered 188Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the 188Re-liposome-treated rats.Results: By using bioluminescent imaging, the well-established reporter cell line (F98luc showed a high relationship between cell number and its bioluminescent intensity (R2=0.99 in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of 188Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the 188Re-liposome-treated group than the control group (P<0.05. As a result, the

  19. Comparison beta absorbed dose from 203Hg, 166Ho and 177LU isotopes in cortex and medulla in tree part kidney and integrated kidney using Monte Carlo method

    Directory of Open Access Journals (Sweden)

    Mohammad Mirzaei

    2015-04-01

    Full Text Available Background: Large quantities of radiopharmaceuticals prescribed for treatment and diagnosis are excreted through kidney. Therefore, radiation unwanted dose is created in kidney. As a result, exact calculation of prescribed medicine amount is important. In Mird pamphlet, 5 kidneys have considered in ellipsoidal shape that radiopharmaceutical is uniform distributed in them and gamma absorption fraction is calculated and recorded in the tables and the fraction of beta absorption is considered unit. While, kidney has internal organs and radioisotope is not uniform distributed in and beta absorbed fraction is not unit. Material and method: In this research, for the first time kidney is considered integrated shape and for the second time has been considered that it is consisted of three areas, pelvis, medulla and cortex. It is supposed that radiopharmaceutical is distributed in medulla. Then, beta absorbed dose is calculated in medulla and cortex using MCNPX code and is compared with integrated kidney results. Resuts: This research has been showed that beta absorbed dose from 203Hg, 166Ho and 177Lu isotopes in medulla is four times as much as dose in integrated kidney and beta dose in cortex is 0.004 to 0.012 times as much as beta dose in integrated kidney. Conclusion: Internal structure of kidney should be considered in simulation to achieve a more accurate prescribed dose. It is recommended that simulation results of three areas kidney are replaced with integrated kidney to prevent from renal toxicity.

  20. Occupational doses in neuroendocrine tumors by using {sup 177}Lu DOTATATE; Doses ocupacionais em tratamento de tumores neuroendocrinos utilizando {sup 17'}7Lu DOTATATE

    Energy Technology Data Exchange (ETDEWEB)

    Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de, E-mail: gustavo@ird.gov.b, E-mail: lidia@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2011-10-26

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of {sup 177}Lu DOTATATE radiopharmaceutical which is a type of treatment presently used in the experimental form in Brazil and, therefore, not contemplated in norms or specific use. This research studied the occupational doses of this treatment and suggested guidelines or rules of procedures viewing the radiological protection of workers involved and the public. The treatment were followed up by using two types of radiation detection, one a scintillator and a Geiger-Muller, and the measurements were performed in a public hospital at Rio de Janeiro and the other in a private hospital at Sao Paulo. It was observed that the equivalent occupational doses can variate from 160 {mu}Sv to 450 {mu}Sv, in function of operator, of stage of manipulation, and of the administration method, which can be through the use of infusion pump or manual injection. The use of infusion pump is highly recommended and the hospitalization of the patient until the dose rate measured at 1 m does not surpass 20 {mu}Sv/h

  1. Development of a lyophilized formulation for preparing the radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20; Desarrollo de una formulacion liofilizada para la preparacion del radiofarmaco {sup 177}-DOTA-Anti-CD20

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

    The radiolabeled proteins are molecules of interest in nuclear medicine for their diagnostic and therapeutic application in cancer. Antibodies, such as chimeric monoclonal antibody Anti-CD20 rituximab, have established themselves as suitable vectors of radionuclides (e.g. {sup 177}Lu) , introducing high affinity by the surface antigens over- expressed and widely distributed in cells involved in certain diseases. The aim of this work was to design, optimize and document the production process of radiopharmaceutical {sup 177}Lu-DOTA-Anti-CD20 for sanitary registration request to the Comision Federal para la Proteccion contra Riesgos Sanitarios (COFEPRIS). First, a raw material analysis using the Ft-Mir technique and gamma spectrometry was performed. Then, was carried out the development of the lyophilized formulation for the preparation of {sup 177}Lu-DOTA-Anti-CD20, in which an ANOVA was performed where the dependent variable was the radiochemical purity. The optimal pharmaceutical formulation was: 5 mg DOTA-CD20 and 80 mg Mannitol to be reconstituted with 1 m L of acetate buffer 0.25 M, ph 7, with an incubation time of 15 min at 37 degrees Celsius in a dry bath. Once completed the development of the lyophilized formulation, we proceeded to the optimization of the production process, development and validation of the analytical method. Three batches were prepared under protocols of Good Manufacturing Practice, which met pre-established specifications as sterile and endotoxin-free of bacterial formulations, with greater that 95% of radiochemical purity. Currently, is conducting the study of shelf stability. Upon completion of the stability studies, the legal record of {sup 177}Lu-DOTA-Anti-CD20 will be integrated with documented evidence of the quality and stability of the formulation of this radiopharmaceutical. (Author)

  2. 肿瘤骨转移疼痛患者对188Re-HEDP的耐受性研究%The tolerance to 188Re-HEDP treatment in patients with bone pain from osseous metastases

    Institute of Scientific and Technical Information of China (English)

    程爱萍; 陈绍亮; 刘文官; 陈雪芬; 许长德

    2011-01-01

    Objective To study the tolerance to 188Re-1-hydroxy-1 ,1-ethylidene disodium phosphonate(HEDP) in patients with bone pain caused by osseous metastases. Methods Thirty-one patients(10with prostate cancer, 9 with breast cancer, 3 with lung cancer, 5 with liver cancer, 2 with rectal cancer, 1with esophageal cancer and 1 with renal cancer) received a single injection dose of 188Re-HEDP. The patients were divided into four groups according to the injection dose: 20 MBq/kg (6 patients), 30 MBq/kg(6 patients), 40 MBq/kg (9 patients), and 50 MBq/kg (10 patients). Haematological toxicity (WHO grading) of grade Ⅲ- Ⅳ was considered unacceptable. Vital signs and adverse effects after injection were recorded for 8 weeks. Blood counts were measured weekly during a period of 8 weeks. Biochemical parameters and electrocardiogram were assayed at week 4 and 8. Statistical analysis was performed for per-protocol (pp) population (t-test). Results Twenty-seven patients belonged to PP population with 5 in the group of 20 MBq/kg, 5 in the group of 30 MBq/kg, 8 in the group of 40 MBq/kg and 9 in the group of 50 MBq/kg.No obvious adverse effects and no significant change of vital signs, electrocardiogram, liver and renal function were found after injection. Alkaline phosphatase was slightly higher than baseline at week 4 and 8 after therapy, but the difference was not statistically significant. In the 20 MBq/kg group, reversible grade Ⅰ leucopenia was noted in 1 patient. In the 30 MBq/kg group, 2 patients showed reversible grade Ⅰ leucopenia including 1 alone with reversible grade Ⅲ thrombopenia. In the 40 MBq/kg group, reversible grade Ⅰ leucopenia and thrombopenia was observed in 1 patient and reversible grade Ⅱ leucopenia and thrombopenia in another patient. In the .50 MBq/kg group, 3 patients showed reversible grade Ⅱ leucopenia. The lowest level of thrombopenia was at week 4(143.5 × 109/L), leucopenia at week 6 (5.4 × 109/L) and anaemia at week 8(t = 3.1325, 3

  3. Formulation and evaluation of freeze-dried DOTMP kit for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP at the hospital radiopharmacy

    Energy Technology Data Exchange (ETDEWEB)

    Das, Tapas; Banerjee, Sharmila [Bhabha Atomic Research Centre, Radiopharmaceuticals Chemistry Section, Mumbai (India); Chakraborty, Sudipta [Bhabha Atomic Research Centre, Isotope Production and Applications Div., Mumbai (India); Sarma, Haladhar D. [Bhabha Atomic Research Centre, Radiation Biology and Health Sciences Div., Mumbai (India)

    2015-07-01

    The objective of the present work is to develop and evaluate freeze-dried DOTMP kit, which could be utilized for the convenient and single-step preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP, both of which have shown potential as alternative agents for metastatic bone pain palliation. Freeze-dried DOTMP kits, each comprising a lyophilized mixture of 20 mg DOTMP and 8.75 mg NaOH, were prepared. The kits were used for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP complexes. The agents were prepared by dissolving the lyophilized powder in 1 mL of normal saline and incubating with {sup 177}LuCl{sub 3} or {sup 153}SmCl{sub 3}, produced in-house, for 15 min at room temperature. Pharmacokinetic behavior and biological distribution of the agents were studied by carrying out biodistribution as well as scintigraphic studies in normal male Wistar rats. Shelf-life of the freeze-dried kits was also ascertained. Clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP complexes, comprising up to 3.7 GBq (100 mCi) of activity, were prepared with > 99% radiochemical purity using the freeze-dried kits. The complexes exhibited high in vitro stability when stored at room temperature. Biological studies showed selective skeletal accumulation and insignificant uptake of the radiotracers in any of the vital organs/tissue. The non-accumulated activity exhibited primary urinary clearance. The kits had a shelf-life of 2 years when stored at 4 C temperature. Freeze-dried DOTMP kits, suitable for the preparation of clinical-scale {sup 177}Lu-DOTMP and {sup 153}Sm-DOTMP, have been developed and the radiochemical and biological behaviors of the radiolabeled agents have been studied. The use of the kit at the hospital radiopharmacy is expected to make the preparations easy and convenient. This in turn will enable the widespread dissemination of these promising agents towards their application for regular use.

  4. {sup 99m}Tc(V)DMSA quantitatively predicts {sup 188}Re(V)DMSA distribution in patients with prostate cancer metastatic to bone

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J.; Kettle, A.G.; O' Doherty, M.J.; Coakley, A.J. [Kent and Canterbury Hospital, Canterbury (United Kingdom). Nuclear Medicine Dept.; Knapp, F.F. Jr. [Nuclear Medicine Group, Oak Ridge National Lab., Oak Ridge, TN (United States)

    2000-09-01

    Rhenium-188 dimercaptosuccinic acid complex [{sup 188}Re(V)DMSA], a potential therapeutic analogue of the tumour imaging agent {sup 99m}Tc(V)DMSA, is selectively taken up in bone metastases in patients with prostate cancer. It would be helpful in planning palliative radionuclide therapy if {sup 99m}Tc(V)DMSA could be used to predict tumour and kidney retention of {sup 188}Re(V)DMSA. The aim of this study was to determine the correlation between tumour-to-normal tissue ratios and kidney-to-soft tissue ratios of {sup 99m}Tc(V)DMSA and {sup 188}Re(V)DMSA. This would determine whether a scan with {sup 99m}Tc(V)DMSA, could be used to identify patients for whom {sup 188}Re(V)DMSA treatment would be contra-indicated, and enable prediction of relative kidney and tumour radiation absorbed dose in {sup 188}Re(V)DMSA treatment. Ten patients with prostate carcinoma were recruited following observation of disseminated bone metastases on a recent {sup 99m}Tc-hydroxydiphosphonate bone scan. Whole-body planar scans were obtained at ca. 4 h and 24 h after hydration and injection of 600 MBq {sup 99m}Tc(V)DMSA, and a week later, at similar times after hydration and injection of 370 MBq {sup 188}Re(V)DMSA. A triple-energy window (TEW) scatter correction was applied to the {sup 188}Re scans. Counts per pixel were determined in regions of interest drawn over metastatic sites, kidneys and normal soft tissue. Tumour-to-soft tissue ratios were significantly lower (by a factor of approximately 0.8 after the TEW was applied) on {sup 188}Re scans than on {sup 99m}Tc scans, but the two were highly linearly correlated both in all individual patients and in tumours pooled from all patients together both at 4 h and at 24 h. Kidney-to-soft tissue ratios were similarly correlated and were lower for {sup 188}Re than for {sup 99m}Tc by a similar factor. Both tumour- and kidney-to-soft tissue ratios increased between 4 and 24 h but the latter increased more. In conclusion, only minor differences were

  5. Outcome of peptide receptor radionuclide therapy with {sup 177}Lu-octreotate in advanced grade 1/2 pancreatic neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Ezziddin, Samer; Khalaf, Feras; Vanezi, Maria; Haslerud, Torjan; Zreiqat, Abdullah Al; Biersack, Hans-Juergen; Sabet, Amir [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin [University Hospital, Department of Internal Medicine and Oncology, Bonn (Germany); Willinek, Winfried [University Hospital, Department of Radiology, Bonn (Germany)

    2014-05-15

    The clinical benefit of peptide receptor radionuclide therapy (PRRT) in patients with pancreatic neuroendocrine tumours (pNET) has not yet been well described and defined in its full extent due to limited data in this tumour subgroup. This study was intended to obtain robust, comparative data on the outcome and toxicity of standardized PRRT with {sup 177}Lu-octreotate in a well-characterized population of patients with advanced pNET of grade 1/2 (G1/2). We retrospectively analysed a cohort of 68 pNET patients with inoperable metastatic disease consecutively treated with {sup 177}Lu-octreotate (four intended cycles at 3-monthly intervals; mean activity per cycle 8.0 GBq). Of these 68 patients, 46 (67.6 %) had documented morphological tumour progression during the 12 months before initiation of treatment, and PRRT was the first-line systemic therapy in 35 patients (51.5 %). Response was evaluated according to modified Southwest Oncology Group (SWOG) criteria and additionally with Response Criteria in Solid Tumors (RECIST) 1.1. Survival was analysed using Kaplan-Meier curves and Cox proportional hazards model for univariate and multivariate analyses. Toxicity was assessed by standard follow-up laboratory work-up including blood count, and liver and renal function, supplemented with serial {sup 99m}Tc-DTPA clearance measurements. The median follow-up period was 58 months (range 4 - 112). Reversible haematotoxicity (grade 3 or more) occurred in four patients (5.9 %). No significant nephrotoxicity (grade 3 or more) was observed. Treatment responses (SWOG criteria) consisted of a partial response in 41 patients (60.3 %), a minor response in 8 (11.8 %), stable disease in 9 (13.2 %), and progressive disease in 10 (14.7 %). Median progression-free survival (PFS) and overall survival (OS) were 34 (95 % CI 26 - 42) and 53 months (95 % CI 46 - 60), respectively. A G1 proliferation status was associated with longer PFS (p = 0.04) and OS (p = 0.044) in the multivariate analysis

  6. The experimental study on the radioimmunotherapy of the nasopharyngeal carcinoma overexpressing HER2/neu in nude mice model with intratumoral injection of {sup 188}Re-herceptin

    Energy Technology Data Exchange (ETDEWEB)

    Li Guiping [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China) and Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China)]. E-mail: ligp@fimmu.com; Wang Yongxian [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, the Chinese Academy of Sciences, Shanghai, 201800 (China)]. E-mail: yongxianw@163.com; Huang Kai [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Hui [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Peng Wuhe [Department of Nuclear Medicine, Nanfang Hospital, First Military Medical University, Guangzhou, 510515 (China); Zhang Chunfu [Radiopharmaceutical Research Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai, 201800 (China)

    2005-01-01

    The therapeutic efficacy of radioimmunotherapy (RIT) of {sup 188}Re-labeled herceptin, which is a humanized anti-p185-HER2/neu monoclonal antibody (mAb), was studied. The nude mice bearing nasopharyngeal carcinoma (NPC) expressing HER2/neu protooncogene were injected with {sup 188}Re-herceptin intratumorally and intravenously. The biodistribution was observed on day 2 (n=3). The tumor growth inhibition rate (IR) was determined by measurement of tumor volume. In the intratumorally treated mice, tumor uptake of {sup 188}Re-herceptin was significantly greater than in the intravenously treated mice [11.53% injected dose (ID)/g vs. 2.79% ID/g at 48 h], and lower normal organ uptake was also seen. The intratumoral administration of {sup 188}Re-herceptin caused greater inhibition of tumor growth at the fourth week as compared to the intravenous administration. It is concluded that intratumoral administration of {sup 188}Re-herceptin makes high level of radioactivity retained in tumor with significantly lower radioactivity retained in normal tissues, and provides a more effective regional therapy for NPC overexpressing HER2/neu.

  7. Synthesis and stability test of radioimmunoconjugate 177Lu-DOTA-F(ab′2-trastuzumab for theranostic agent of HER2 positive breast cancer

    Directory of Open Access Journals (Sweden)

    Sandra Hermanto

    2016-10-01

    Full Text Available The use of trastuzumab as intact IgG labeling radionuclide for HER2 positive breast cancer theranostic agent is not ideal because it is slowly eliminated from the blood and normal tissues resulting in low tumor/blood (T/B and tumor/normal tissue (T/NT ratios. To overcome this limitation, we developed the trastuzumab F(ab′2 fragments and radiolabeling of the fragments by β and γ-particle of Lutetium-177. F(ab2 fragments were produced by digestion of trastuzumab IgG (Herceptin with pepsin for 18 h at 37 °C. The F(ab′2 fragment fractionated in PD-10 column, followed by the conjugation with 2-(4-isothiocyanatobenzyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (p-SCN-Bn-DOTA as a metal chelator and radiolabeling with 177LuCl3. Molecular weight of fragments was calculated by LCMS (Liquid Chromatography Mass Spectroscopy and the radiochemical purity was evaluated by ITLC-SG (Instan Thin Layer Chromatography. Our study showed that the purity of F(ab′2 fragment generated by PD-10 fractions was >98% and the molecular weight of F(ab′2 was 98.35 kDa. The average numbers of pSCN-Bn-DOTA chelates per antibody fragment were 5.03 ± 1.5 and the optimum conjugation reactions was performed at molar ratio 20:1 (chelator to antibody. The stability test of the radioimmunoconjugate in the human serum albumin (HSA at 37 °C showed the radiochemical purity was 91.96 ± 0.26% after 96 h storage. This indicated that the radioimmunoconjugate is relatively stable when applied to the human body's physiological condition.

  8. Rapid blood clearance and lack of long-term renal toxicity of {sup 177}Lu-DOTATATE enables shortening of renoprotective amino acid infusion

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); Jackson, Price [Peter MacCallum Cancer Centre, Department of Physical Sciences, Melbourne (Australia); Hofman, Michael S.; Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne (Australia); The University of Melbourne, Departments of Medicine and Radiology, Melbourne (Australia); Beauregard, Jean-Mathieu [Universite Laval, Department of Radiology, Quebec City (Canada); Zannino, Diana [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne (Australia)

    2013-12-15

    The aim of the study was to investigate the feasibility of shortening the recommended 4-h renoprotective amino acid infusion in patients receiving peptide receptor chemoradionuclide therapy (PRCRT) using radiosensitizing 5-fluorouracil. We evaluated the clearance of radiopeptide from the blood, long-term nephrotoxicity in patients undergoing PRCRT with the conventional 4-h amino acid infusion and renal uptake in patients receiving an abbreviated infusion. The whole-blood clearance of {sup 177}Lu-DOTA-octreotate (LuTate) was measured in 13 patients receiving PRCRT. A retrospective analysis of short-term and long-term changes in glomerular filtration rate (GFR) in 96 consecutive patients receiving a 4-h infusion was performed. Renal LuTate retention estimated using quantitative SPECT/CT in 22 cycles delivered with a 2.5-h amino acid infusion was compared with that in 72 cycles with the 4-h infusion. LuTate demonstrated biexponential blood clearance with an initial clearance half-time of 21 min. Approximately 88 % of blood activity was cleared within 2 h. With the 4-h protocol, there was no significant change in GFR (1.2 ml/min mean increase from baseline; 95 % CI -6.9 to 4.4 ml/min) and no grade 3 or 4 nephrotoxicity at the end of induction PRCRT. The long-term decline in GFR after a median follow up of 22 months was 2.2 ml/min per year. There was no significant difference in the renal LuTate retention measured in patients receiving a 2.5-h amino acid infusion compared to those who had a 4-h infusion. The greatest renal exposure to circulating radiopeptide occurs in the first 1 - 2 h after injection. This, combined with the safety of LuTate PRCRT, allows consideration of an abbreviated amino acid infusion, increasing patient convenience and reducing human resource allocation. (orig.)

  9. Feasibility and utility of re-treatment with {sup 177}Lu-DOTATATE in GEP-NENs relapsed after treatment with {sup 90}Y-DOTATOC

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine Unit, Meldola, FC (Italy); Bodei, Lisa [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Ibrahim, Toni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); D' Errico, Vincenzo [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2015-12-15

    Peptide receptor radionuclide therapy (PRRT) is a valid therapy for grade 1/2 gastroenteropancreatic (GEP) neuroendocrine neoplasms (NENs). Although a median progression-free survival (PFS) of more than 20 months is frequently observed, the majority of patients relapse after 2 - 3 years. In the present study, we investigated the use of low dosage re-treatment with {sup 177}Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with {sup 90}Y-DOTATOC (Y-PRRT). Upon tumour progression, 26 patients with a PFS of at least 12 months after Y-PRRT were consecutively enrolled in a phase II study of re-treatment with Lu-PRRT. All patients had preserved kidney and haematological parameters and received 14.8 - 18.5 GBq of Lu-PRRT in four or five cycles. The disease control rate (DCR), toxicity, PFS and prognostic factors were evaluated. Median total activity of Lu-PRRT was 16.5 GBq in five cycles. The DCR was 84.6 %, median PFS was 22 months (95 % CI 16 months - not reached) compared to 28 months (95 % CI 20 - 36 months) after Y-PRRT. Tumour burden and number of liver metastases were important prognostic factors. Toxicity was mild after Lu-PRRT re-treatment in the majority of patients, with only two patients with grade 2 and one with grade 3 bone marrow toxicity; one patient had grade 2 and one grade 3 renal toxicity. Patients with GEP-NEN who have previously responded to Y-PRRT are suitable candidates for Lu-PRRT re-treatment on progression. Although our sample size was limited, low-dosage Lu-PRRT was safe, and led to DCR and PFS rates comparable with those observed when Y-PRRT was used as primary treatment. (orig.)

  10. Influence of biological assay conditions on stability assessment of radiometal-labelled peptides exemplified using a {sup 177}Lu-DOTA-minigastrin derivative

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Meltem [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Helbok, Anna; Guggenberg, Elisabeth von [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria); Ozsoy, Y. [Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul University, 34116, Istanbul (Turkey); Kabasakal, Levent [Department of Nuclear Medicine, Cerrahpasa Medical Faculty, 34098, Istanbul (Turkey); Kremser, Leopold [Division of Clinical Biochemistry, Protein Micro-Analysis Facility, Biocenter, Medical University Innsbruck, A-6020, Innsbruck (Austria); Decristoforo, Clemens, E-mail: clemens.decristoforo@uki.a [Clinical Department of Nuclear Medicine, Medical University Innsbruck, A-6020, Innsbruck (Austria)

    2011-02-15

    Introduction: Lack of correlation between in vitro and in vivo stability is a general problem for the development of radiopeptides especially in the case of minigastrin derivatives for therapeutic applications. In this study, we compared the influence of experimental conditions on radiopeptide stability results in vitro using a model Minigastrin (MG) analogue labelled with Lu-177. Additionally, we attempted to characterize the main serum enzymatic cleavage sites by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) analysis. Methods: In vitro stability of a DOTA-minigastrin derivative ({sup 177}Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH{sub 2}) was tested in serum, rat tissue homogenates and two different standardised enzymatic mixtures. Quantification of the metabolised radiopeptides at different time intervals was performed using reversed-phase high-performance liquid chromatography (RP-HPLC). Metabolites were characterised by MALDI-TOF-MS. Urine was collected after 15 min p.i. into the mice and compared with in vitro metabolites by RP-HPLC. Results: Faster degradation of the radiopeptide was found in blood in comparison with plasma and serum incubation and in components from rats faster than from human origin. Fast degradation was observed in kidney and liver homogenates as well as in standardised enzymatic mixtures, also revealing variations in the metabolic profile. In urine, no intact peptide was detected already 5 min post injection. MALDI-TOF-MS revealed major cleavage sites at the carboxy terminus of the peptide. Conclusion: Very variable results may be found when different kind of incubation media for testing radiopeptide stabilities is used. Serum incubation studies may overestimate stability; therefore, results should be interpreted with care and combined with alternative in vitro and in vivo investigations.

  11. A YAP camera for the biodistribution of {sup 188}Re conjugated with Hyaluronic-Acid in 'in vivo' systems

    Energy Technology Data Exchange (ETDEWEB)

    Antoccia, A. [Department of Biology, Roma3 University (Italy); INFN, Roma3 (Italy); Baldazzi, G. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); Banzato, A. [Department of Oncology and Surgical Sciences, Padova University (Italy); Bello, M. [INFN, National Laboratories, Legnaro (Italy); Department of Physics, Padova University (Italy); Boccaccio, P. [INFN, National Laboratories, Legnaro (Italy); Bollini, D. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); De Notaristefani, F. [INFN, Roma3 (Italy); Department of Electronic Engineering, Roma3 University and INFN (Italy); Mazzi, U. [Department of Pharmaceutical Sciences, Padova University (Italy); Alafort, L.M. [Department of Pharmaceutical Sciences, Padova University (Italy); Moschini, G. [INFN, National Laboratories, Legnaro (Italy); Department of Physics, Padova University (Italy); Navarria, F.L. [Department of Physics, Bologna University (Italy); INFN, Bologna (Italy); Pani, R. [Department of Experimental Medecine and Pathology, Roma1 University (Italy); INFN, Roma1 (Italy); Perrotta, A. [INFN, Bologna (Italy)]. E-mail: perrotta@bo.infn.it; Rosato, A. [Department of Oncology and Surgical Sciences, Padova University (Italy); Istituto Oncologico Veneto, Padova (Italy); Tanzarella, C. [Department of Biology, Roma3 University (Italy); Uzunov, N.M. [INFN, National Laboratories, Legnaro (Italy); Dept. Natural Sciences, Shumen Univ. (Bulgaria)

    2007-02-01

    The aim of the SCINTIRAD experiment is to determine the radio-response of {sup 188}Rhenium (Re) in in vitro cells and the biodistribution in different organs of in vivo mice, and subsequently to assess the therapeutic effect on liver tumours induced in mice. Both the {gamma}- and {beta}- emissions of {sup 188}Re have been exploited in the experiment. The in vivo biodistribution in mice was studied also with a {gamma}-camera using different parallel hole collimators. In the {sup 188}Re spectrum, while the 155 keV {gamma}-peak is useful for imaging, the photons emitted at larger energies and the {beta}-particles act as noise in the image reconstruction. The {gamma}-cameras previously used to image biodistributions obtained with {sup 99}Tc are, therefore, not optimized for use with {sup 188}Re. A new setup of the {gamma}-camera has been studied for {sup 188}Re: 66x66 YAP:Ce crystals (0.6x0.6x10 mm{sup 3}, 5 {mu}m optical insulation) guarantee a FOV of 40x40 mm{sup 2}, a Hamamatsu R2486 PSPMT, 3 in. diameter, converts their light into an electrical signal and allows reconstructing the spatial coordinates of the light spot; incoming photon directions are selected through a lead collimator with 1.5 mm diameter hexagonal holes, 0.18 mm septa, 40 mm thickness. Using this setup, results have been obtained both with {sup 99}Tc filled and {sup 188}Re filled capillaries and wells. The energy spectrum of the collected photons and the spatial resolutions obtainable with the {sup 188}Re source will be presented.

  12. Studies on biodistribution and imaging of 188Re labeled insulin-like growth factor-1 analogue in nude mice bearing human pancreatic carcinoma%188Re-胰岛素样生长因子1类似物在荷人胰腺癌裸鼠体内分布及其显像研究

    Institute of Scientific and Technical Information of China (English)

    邓胜明; 张玮; 章斌; 罗贤文; 吴翼伟

    2008-01-01

    目的 研究188Re标记胰岛素样生长因子l类似物(IGF-1A)在荷人胰腺癌裸鼠体内的分布及其显像.方法 ①直接法标记188Re-IGF-1A并测定标记率.②建立荷人胰腺癌Patu8988裸鼠模型.③188Re-IGF-1A经瘤内注射荷人胰腺癌裸鼠瘤内,分别于注射后15 min、1 h、4 h、24 h、3 d、5 d进行SPECT平面显像.④188ReO4-经瘤内注射后15 min、1 h、2 h、4 h、24 h进行显像,取各时间组裸鼠(n=4)脏器和肿瘤组织,计算每克组织百分注入剂量(%ID/g)及肿瘤/非肿瘤组织放射性摄取比值(T/NT).结果 ①188Re-IGF-1A标记率为(94.07±0.32)%.②瘤内注射188Re-IGF-1A后,肿瘤部位放射性积聚量4 h内差异无统计学意义(F=1.622,P>0.05),且随时间延长,肿瘤与其他脏器的T/NT呈上升趋势,其中肿瘤/肌肉在5 d时最高,达到6531.79±4930.26.③瘤内注射188ReO4-后,在体内初始主要分布于甲状腺、胃、肿瘤、血液,随时间延长,肿瘤部位放射性计数迅速下降.④在24 h,瘤内注射188Re-IGF-1A组肿瘤及肾脏内%ID/g较188ReO4-组高,两者有统计学差异(t=5.877,t=13.287,P<0.01);两组肿瘤内%ID/g比值在24 h达到最高,为74.10倍.⑤瘤内注射188Re-IGF-1A后,SPECT平面显像见瘤内浓聚,5 d时仅见肿瘤部位显影.结论 188Re-IGF-1A对胰腺癌具有良好的亲和力,在肿瘤部位有较高的T/NT,可望作为胰腺癌治疗的药物.%Objective To evaluate the biodistribution and planar gamma carnera jmaging characteristics of 188Re labeled insulin-like growth factor 1 analogue(188Re-IGF-1A)in tumor-bearing mice.Methods ①To label IGF-1A with 188Re directly and to determine the labeling efficiency.②To establish nude mice model which beating human pancreatic carcinoma cell Patu8988.③To scan those nude mice at 15 min,1 h,4 h,24 h,3 d and 5 d after intratumor injection with 188Re-IGF-1A into their tumors.④To scan those nude mice at 15min,1 h,2h,4 h and24 h after intratumor injection with 188ReO4-into their

  13. Role of {sup 18}FDG PET/CT in patients treated with {sup 177}Lu-DOTATATE for advanced differentiated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Matteucci, Federica [Cancer Institute of Romagna (IRST), Unit of Radiometabolic Medicine, Meldola, FC (Italy); Nanni, Oriana; Scarpi, Emanuela [Cancer Institute of Romagna (IRST), Unit of Biostatistics and Clinical Trials, Meldola, FC (Italy); Bodei, Lisa; Gilardi, Laura; Paganelli, Giovanni [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Nicoletti, Stefania [Cancer Institute of Romagna (IRST), Unit of Medical Oncology, Meldola, FC (Italy)

    2013-06-15

    The prognostic value of FDG PET for neuroendocrine tumours (NETs) has been reported. In this study we evaluated the role of FDG PET in predicting response and progression-free survival (PFS) after {sup 177}Lu-DOTATATE peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced well-differentiated grade 1/2 NETs. We retrospectively evaluated 52 patients with progressive advanced NETs overexpressing somatostatin receptors and treated with Lu-PRRT with a cumulative activity up to 27.7 GBq divided into five courses. According to WHO 2010/ENETS classification, patients were stratified into two groups: those with grade 1 tumour (Ki-67 index {<=}2 %, 19 patients), and those with grade 2 tumour (Ki-67 index >3 % to <20 %, 33 patients). On the basis of the FDG PET scan, 33 patients were classified as PET-positive (PET+) and 19 as PET-negative (PET-). FDG PET was positive in 57 % of patients with grade 1 NET and in 66 % of patients with grade 2 NET, and the rates of disease control (DC, i.e. complete response + partial response + stable disease) in grade 1 and grade 2 patients were 95 % and 79 %, respectively (P = 0.232). In PET- and PET+ patients, the DC rates were 100 % and 76 % (P = 0.020) with a PFS of 32 and 20 months, respectively (P = 0.033). Of the PET+ patients with grade 1 NET, 91 % showed disease control, whereas about one in three PET+ patients with grade 2 NET (32 %) progressed after Lu-PRRT (DC rate 68 %). These results suggest that FDG PET evaluation is useful for predicting response to Lu-PRRT in patients with grade 1/2 advanced NETs. Notably, none of PET- patients had progressed at the first follow-up examination after Lu-PRRT. Grade 2 NET and PET+ (arbitrary SUV cutoff >2.5) were frequently associated with more aggressive disease. PET+ patients with grade 2 NET, 32 % of whom did not respond to Lu-PRRT monotherapy, might benefit from more intensive therapy protocols, such as the combination of chemotherapy and PRRT. (orig.)

  14. Peptide receptor radionuclide therapy with {sup 90}Y/{sup 177}Lu-labelled peptides for inoperable head and neck paragangliomas (glomus tumours)

    Energy Technology Data Exchange (ETDEWEB)

    Puranik, Ameya D.; Kulkarni, Harshad R.; Singh, Aviral; Baum, Richard P. [Zentralklinik Bad Berka, THERANOSTICS Centre for Molecular Radiotherapy and Molecular Imaging, ENETS Center of Excellence, Bad Berka (Germany)

    2015-07-15

    Head and neck paragangliomas (HNPGLs) are rare tumours arising from autonomic nervous system ganglia. Although surgery offers the best chance of complete cure, there is associated morbidity due to the crucial location of these tumours. Radiotherapy arrests tumour growth and provides symptomatic improvement, but has long-term consequences. These tumours express somatostatin receptors (SSTR) and hence peptide receptor radionuclide therapy (PRRT) is now a treatment option. We assessed the molecular, morphological and clinical responses of inoperable HNPGLs to PRRT. Nine patients with inoperable HNPGL assessed between June 2006 and June 2014 were included. Four patients had a solitary lesion, four had multifocal involvement and one had distant metastases (bone and lungs). The patients were treated with PRRT using {sup 90}Y/{sup 177}Lu-labelled peptides after positive confirmation of SSTR expression on {sup 68}Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with {sup 68}Ga-DOTATOC PET/CT was carried out every 6 months to assess response to treatment. Clinical (symptomatic) response was also assessed. Based on molecular response (EORTC) criteria, four of the nine patients showed a partial molecular response to treatment seen as significant decreases in SUV{sub max}, accompanied by a reduction in tumour size. Five patients showed stable disease on both molecular and morphological criteria. Six out of nine patients were symptomatic at presentation with manifestations of cranial nerve involvement, bone destruction at the primary site and metastatic bone pain. Molecular responses were correlated with symptomatic improvement in four out of these six patients; while two patients showed small reductions in tumour size and SUV{sub max}. The three asymptomatic patients showed no new lesions or symptomatic worsening. PRRT was effective in all patients, with no disease worsening seen, either in the form of neurological symptoms or

  15. Peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE in advanced bronchial carcinoids: prognostic role of thyroid transcription factor 1 and {sup 18}F-FDG PET

    Energy Technology Data Exchange (ETDEWEB)

    Ianniello, Annarita; Sansovini, Maddalena; Severi, Stefano; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Unit, Meldola (Italy); Grana, Chiara Maria [European Institute of Oncology Milan (IEO), Division of Nuclear Medicine, Milan (Italy); Massri, Katrin [Ospedale San Luca, Nuclear Medicine, Department of Radiology, Lucca (Italy); Bongiovanni, Alberto [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Osteoncology and Rare Tumors Center, Meldola (Italy); Antonuzzo, Lorenzo [AOU Careggi, SC Oncologia Medica 1, Firenze (Italy); Di Iorio, Valentina [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Sarnelli, Anna [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Medical Physics Unit, Meldola (Italy); Monti, Manuela; Scarpi, Emanuela [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy)

    2016-06-15

    Typical and atypical carcinoids (TC and AC) represent 20 - 25 % of all neuroendocrine tumours. No standard therapeutic approach is available for patients with advanced disease. The aim of this phase II study was to investigate the efficacy and safety of peptide receptor radionuclide therapy with {sup 177}Lu-DOTATATE (Lu-PRRT) and the role of thyroid transcription factor 1 (TTF-1) and {sup 18}F-FDG PET as prognostic factors in patients with advanced TC or AC. A total of 34 consecutive patients with radiologically documented progressive disease were treated with Lu-PRRT at a therapeutic cumulative activity of 18.5 or 27.8 GBq in four or five cycles according to the patient's kidney function and bone marrow reserve. Information on TTF-1 was available in all patients. FDG PET studies prior to Lu-PRRT were available in 29 patients. The median follow-up was 29 months (range 7 - 69 months). The disease control rate (DCR) in patients with TC was 80 %: 6 % complete response, 27 % partial response and 47 % stable disease. The median progression-free survival (mPFS) was 20.1 months (95 % CI 11.8 - 26.8 months). Stable disease was achieved in 47 % of patients with AC with a mPFS of 15.7 months (95 % CI 10.6 - 25.9 months). No major acute or delayed toxicity occurred in either group or with either cumulative activity. mPFS in patients with TTF-1-negative TC was 26.3 months (95 % CI 12.9 - 45.2 months), but in patients with TTF-1-positive TC mPFS was 7.2 months (4.2 - 14.0 months; p = 0.0009). FDG PET was negative in 13 patients (10 TC and 3 AC) and positive in 16 patients (4 TC and 12 AC). The mPFS in the FDG PET-negative group was 26.4 months (95 % CI 14.2 - 48.9 months) and 15.3 months (11.7 - 31.1 months) in the FDG PET-positive group. Lu-PRRT showed antitumour activity in terms of DCR and PFS and proved safe, even in patients with a higher risk of side effects. TTF-1 would appear to be a prognostic factor. FDG PET positivity in bronchial carcinoids is a hallmark of

  16. Radiosynovectomy of Painful Synovitis of Knee Joints Due to Rheumatoid Arthritis by Intra-Articular Administration of (177)Lu-Labeled Hydroxyapatite Particulates: First Human Study and Initial Indian Experience.

    Science.gov (United States)

    Shinto, Ajit S; Kamaleshwaran, K K; Chakraborty, Sudipta; Vyshakh, K; Thirumalaisamy, S G; Karthik, S; Nagaprabhu, V N; Vimalnath, K V; Das, Tapas; Banerjee, Sharmila

    2015-01-01

    The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using (177)Lu-labeled hydroxyapatite ((177)Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of (177)Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of (177)Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes

  17. Pre-therapeutic dosimetry of normal organs and tissues of {sup 177}Lu-PSMA-617 prostate-specific membrane antigen (PSMA) inhibitor in patients with castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Kabasakal, Levent; AbuQbeitah, Mohammad; Ayguen, Aslan; Yeyin, Nami [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Medical Faculty, Istanbul (Turkey); Ocak, Meltem [Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Demirci, Emre [Sisli Etfal Training and Research Hospital, Department of Nuclear Medicine, Istanbul (Turkey); Toklu, Turkay [Yeditepe University Medical Faculty, Department of Nuclear Medicine, Istanbul (Turkey)

    2015-12-15

    {sup 177}Lu-617-prostate-specific membrane antigen (PSMA) ligand seems to be a promising tracer for radionuclide therapy of progressive prostate cancer. However, there are no published data regarding the radiation dose given to the normal tissues. The aim of the present study was to estimate the pretreatment radiation doses in patients who will undergo radiometabolic therapy using a tracer amount of {sup 177}Lu-labeled PSMA ligand. The study included seven patients with progressive prostate cancer with a mean age of 63.9 ± 3.9 years. All patients had prior PSMA positron emission tomography (PET) imaging and had intense tracer uptake at the lesions. The injected {sup 177}Lu-PSMA-617 activity ranged from 185 to 210 MBq with a mean of 192.6 ± 11.0 MBq. To evaluate bone marrow absorbed dose 2-cc blood samples were withdrawn in short variable times (3, 15, 30, 60, and 180 min and 24, 48, and 120 h) after injection. Whole-body images were obtained at 4, 24, 48, and 120 h post-injection (p.i.). The geometric mean of anterior and posterior counts was determined through region of interest (ROI) analysis. Attenuation correction was applied using PSMA PET/CT images. The OLINDA/EXM dosimetry program was used for curve fitting, residence time calculation, and absorbed dose calculations. The calculated radiation-absorbed doses for each organ showed substantial variation. The highest radiation estimated doses were calculated for parotid glands and kidneys. Calculated radiation-absorbed doses per megabecquerel were 1.17 ± 0.31 mGy for parotid glands and 0.88 ± 0.40 mGy for kidneys. The radiation dose given to the bone marrow was significantly lower than those of kidney and parotid glands (p < 0.05). The calculated radiation dose to bone marrow was 0.03 ± 0.01 mGy/MBq. Our first results suggested that {sup 177}Lu-PSMA-617 therapy seems to be a safe method. The dose-limiting organ seems to be the parotid glands rather than kidneys and bone marrow. The lesion radiation doses are

  18. Preparation of {sup 188}W/{sup 188}Re generators at base of {sup 188}W-titanium and zirconium tungstates by means of the sol-gel method; Preparacion de generadores {sup 188}W/{sup 188}Re a base de {sup 188}W-tungstenatos de titanio y zirconio mediante el metodo sol-gel

    Energy Technology Data Exchange (ETDEWEB)

    Rosales T, C.J. [Universidad Autonoma del Estado de Mexico, Paseo Colon esq. Paseo Tollocan, 50120 Toluca, Estado de Mexico (Mexico); Monroy G, F.; Rivero G, T.; Rojas N, P. [ININ, Carretera Mexico-Toluca S/N, 52750 Estado de Mexico (Mexico)]. e-mail: c.j.rt@hotmail.com

    2007-07-01

    The {sup 188}Re possess nuclear characteristics that make it attractive for therapeutic application, given their {beta}{sup -} particle emission of high energy 0.764 keV besides the possibility of being able to unite to different ligands. The {sup 188}Re commercial generators use a chromatographic column loaded with alumina where the {sup 188}W is adsorbed and the {sup 188}ReO{sub 4}{sup -} eluted by means of a saline solution. The low capacity of the alumina that only it allows adsorber 0.2% in weight of {sup 188}W demand to use {sup 188}W of a high specific activity. An alternative of production of {sup 188}W / {sup 188}Re generators consists on substituting the high specific activity, for the use of a bigger quantity of {sup 188}W by means of the use of gels with the aid of tungstates. For that, in this work it intends the study of the gel synthesis conditions of {sup 188}W titanium and zirconium tungstates and their effect in the acting of the {sup 188}W / {sup 188}Re generators. The gels were synthesized by means of the sol-gel method starting from titanium and zirconium alcoxis, and solutions of {sup 188}W-sodium tungstates to different pH's. The use of the sol-gel methodology diminishes the time of synthesis of these gels almost in 60% in relation to the precipitation method commonly used. (Author)

  19. In vitro and in vivo evaluation of {sup 177}Lu- and {sup 9}Y-labeled E. coli heat-stable enterotoxin for specific targeting of uroguanylin receptors on human colon cancers

    Energy Technology Data Exchange (ETDEWEB)

    Giblin, Michael F. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States) and Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)]. E-mail: giblinm@health.missouri.edu; Sieckman, Gary L. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Shelton, Tiffani D. [Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Hoffman, Timothy J. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Internal Medicine, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Forte, Leonard R. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Medical Pharmacology and Physiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States); Volkert, Wynn A. [Research Service, Harry S. Truman Memorial Veterans Administration Hospital, Columbia, MO 65201 (United States); Department of Radiology, University of Missouri-Columbia School of Medicine, Columbia, MO 65211 (United States)

    2006-05-15

    The human E. coli heat-stable enterotoxin (ST{sub h}, amino acid sequence N{sup 1}SSNYCCELCCNPACTGCY{sup 19}) binds specifically to the guanylate cyclase C (GC-C) receptor, which is present in high density on the apical surface of normal intestinal epithelial cells as well as on the surface of human colon cancer cells. Analogs of ST{sub h} are currently being used as vectors targeting human colon cancers. Previous studies in our laboratory have focused on development of {sup 111}Indium-labeled ST{sub h} analogs for in vivo imaging applications. Here, we extend the scope of this work to include targeting of the therapeutic radionuclides {sup 9}Y and {sup 177}Lu. The peptide DOTA-F{sup 19}-ST{sub h}(1-19) was synthesized using conventional Fmoc-based solid-phase techniques and refolded in dilute aqueous solution. The peptide was purified by RP-HPLC and characterized by MALDI-TOF MS and in vitro receptor binding assay. The DOTA-conjugate was metallated with nonradioactive Lu(III)Cl{sub 3} and Y(III)Cl{sub 3}, and IC{sub 5} values of 2.6{+-}0.1 and 4.2{+-}0.9 nM were determined for the Lu- and Y-labeled peptides, respectively. {sup 177}Lu(III)Cl{sub 3} and {sup 9}Y(III)Cl{sub 3} labeling yielded tracer preparations that were inseparable by C18 RP-HPLC, indicating that putative differences between Lu-, Y- and In coordination spheres are not observed in the context of labeled ST{sub h} peptides. In vivo biodistribution studies of the {sup 177}Lu-labeled peptide in severe combined immunodeficient (SCID) mice bearing T-84 human cancer tumor xenografts showed rapid clearance from the bloodstream, with >90 %ID in the urine at 1 h pi. Localization of the tracer within tumor xenografts was 1.86{+-}0.91 %ID/g at 1 h pi, a value higher than for all other tissues with the exception of kidney (2.74{+-}0.24 %ID/g). At 24 h pi, >98 %ID was excreted into the urine, and 0.35{+-}0.23 %ID/g remained in tumor, again higher than in all other tissues except kidney (0.91{+-}0.46 %ID

  20. Development of pharmaceuticals with radioactive rhenium for cancer therapy. Production of {sup 186}Re and {sup 188}Re, synthesis of labeled compounds and their biodistributions

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1998-03-01

    Production of the radioactive rhenium isotopes {sup 186}Re and {sup 188}Re, and synthesis of their labeled compounds have been studied together with the biodistributions of the compounds. This work was carried out by the Working Group on Radioactive Rhenium, consisting of researchers of JAERI and some universities, in the Subcommittee for Production and Radiolabeling under the Consultative Committee of Research on Radioisotopes. For {sup 186}Re, production methods by the {sup 185}Re(n,{gamma}){sup 186}Re reaction in a reactor and by the {sup 186}W(p,n){sup 186}Re reaction with an accelerator, which can produce nocarrier-added {sup 186}Re, have been established. For {sup 188}Re, a production method by the double neutron capture reaction of {sup 186}W, which produces a {sup 188}W/{sup 188}Re generator, has been established. For labeling of bisphosphonate, DMSA, DTPA, DADS, aminomethylenephosphonate and some monoclonal antibodies with the radioactive rhenium isotopes, the optimum conditions, including pH, the amounts of reagents and so on, have been determined for each compound. The biodistributions of each of the labeled compounds in mice have been also obtained. (author)

  1. In vivo distribution and metabolism of 188Re-iodized oil-carboxymethyl chitosan-nanoparticles in the S180 tumor-bearing mice%188Re-碘化油-羧甲基壳聚糖-纳米微粒在荷S180肉瘤小鼠体内分布与代谢

    Institute of Scientific and Technical Information of China (English)

    王洪震; 贾正平; 郝彦明; 钱荣勋; 董启榕; 徐又佳

    2011-01-01

    背景:188Re标记的放射性药物在体内发生 Re核索脱落也不会对人体造成严重的辐射损伤.188Re-碘化油有可能成为一种具有临床应用价值的内照射治疗肿瘤的药物.目的:研究羧甲基壳聚糖载药纳米微球的制备及在荷S180肉瘤小鼠体内分布及代谢.方法:将188Re-碘化油通过羧甲基壳聚糖纳米微球包裹,将其注射于荷S180肉瘤小鼠体内,通过 SPECT法观察188Re-碘化油-羧甲基壳聚糖-纳米微粒在荷瘤鼠中的显像.结果与结论:采用羧甲基壳聚糖-纳米微粒对188Re-碘化油标记率达(94.9±0.2)%;肝、肾是188Re-碘化油-羧甲基壳聚糖-纳米微粒的主要分布器官;骨、肌肉、小肠等脏器摄取较少,且随着时间的延长而下降;脑内未测得放射性,各比值随着时间的延长而有增加的趋势,分别在注射显像剂后6~10 h达到峰值.说明羧甲基壳聚糖-纳米微粒对188Re的包裹效果良好;188Re-碘化油-羧甲基壳聚糖-纳米微粒在正常骨、肌肉、小肠基本无摄取,但48 h浓聚于肉瘤组织内,肿瘤与脾、胃、肠、股骨、肌肉、脂肪组织放射性比值高.%BACKGROUND: 188Re labeled radiopharmaceuticals in body occur Re nuclear cable off which will not cause serious radiation damage of the body. 188Re-iodized oil may become a kind of clinical application of drugs within the radiation treatment of cancer.OBJECTIVE: To study preparation of drug-loaded nano-carboxymethyl chitosan microspheres and in vivo distribution and metabolism in the S180 tumor-bearing mice.METHODS: 188Re-lipiodol was wrapped by carboxymethyl chitosan nanoparticles, the wrapped 188Re-lipiodol was injected into the mice bearing S180 sarcoma. Imaging of 188Re-iodized oil-carboxymethyl chitosan-nanoparticles in the tumor-bearing mice was observed by single photon emission computed tomography.RESULTS AND CONCLUSION: Labeling rate of 188Re-lipiodol which labeled by carboxymethyl chitosan-nanoparticles was (94.9±0

  2. {sup 188}Re-HTDD-lipiodol solution as a new therapeutic agent for transhepatic arterial administration in liver cancer: a preclinical study using liver-cancer model in rabbit

    Energy Technology Data Exchange (ETDEWEB)

    Paeng, J. C.; Jeong, J. M.; Lee, Y. S. [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)] [and others

    2001-07-01

    {sup 188}Re-HTDD-lipiodol solution was developed and reported to be a new therapeutic material for transhepatic arterial embolization (TAE) of liver cancer. In this study we compared the tissue retention of {sup 188}Re-HTDD-lipiodol with that of {sup 188}Re-TDD-lipiodol using liver-cancer model in rabbit. Cancer cell line VX2 was inoculated into 7 rabbits and grown up to larger than 3 cm. TAE was performed with {sup 188}Re-TDD-lipiodol in 3 rabbits and with {sup 188}Re-HTDD-lipiodol in 4 rabbits. Conjugated planar scans were performed at 1, 2, 6, 24, 48 hours after TAE. From these images, the mean life of radioactivity retention in tumor was calculated, and the required dose for human application as also calculated from the mean life and MIRDOSE3 software. The mean lifes of radioactivity in liver were 10.2{+-}1.0 hr in TDD group and 17.6{+-}0.8 hr in HTDD group (p<0.001). The required dose for the tumor to be irradiated 50 Gy of radiation was calculated to be 18 mCi of {sup 188}Re-HTDD-lipiodol for 5.7 cm-sized tumor and 88 mCi for 9,7 cm-sized tumor. By the introduction of long chain alkyl group, {sup 188}Re-HTDD-lipiodol showed significantly better tumor retention than that of {sup 188}Re-TDD-lipiodol. And the required dose of radiation for human application was calculated to be 18 {approx} 88 mCi when using {sup 188}Re-HTDD-lipiodol.

  3. Theranostic pretargeted radioimmunotherapy of colorectal cancer xenografts in mice using picomolar affinity {sup 86}Y- or {sup 177}Lu-DOTA-Bn binding scFv C825/GPA33 IgG bispecific immunoconjugates

    Energy Technology Data Exchange (ETDEWEB)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Xu, Hong; Guo, Hong-fen [Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Chalasani, Sandhya; Carrasquillo, Jorge A. [Memorial Sloan Kettering Cancer Center, Department of Radiology, New York, NY (United States); Fung, Edward K. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Jungbluth, Achim [Memorial Sloan Kettering Cancer Center, Department of Pathology, New York, NY (United States); Zanzonico, Pat B.; O' Donoghue, Joseph [Memorial Sloan Kettering Cancer Center, Department of Medical Physics, New York, NY (United States); Smith-Jones, Peter M. [Stony Brook University, Department of Psychiatry and Behavioral Science, Stony Brook, NY (United States); Stony Brook University, Department of Radiology, Stony Brook, NY (United States); Wittrup, K.D. [Massachusetts Institute of Technology, Department of Chemical Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Department of Biological Engineering, Cambridge, MA (United States); Massachusetts Institute of Technology, Koch Institute for Integrative Cancer Research, Cambridge, MA (United States); Cheung, Nai-Kong V. [Memorial Sloan Kettering Cancer Center, Molecular Pharmacology and Chemistry Program, New York, NY (United States); Memorial Sloan Kettering Cancer Center, Department of Pediatrics, New York, NY (United States)

    2016-05-15

    GPA33 is a colorectal cancer (CRC) antigen with unique retention properties after huA33-mediated tumor targeting. We tested a pretargeted radioimmunotherapy (PRIT) approach for CRC using a tetravalent bispecific antibody with dual specificity for GPA33 tumor antigen and DOTA-Bn-(radiolanthanide metal) complex. PRIT was optimized in vivo by titrating sequential intravenous doses of huA33-C825, the dextran-based clearing agent, and the C825 haptens {sup 177}Lu-or {sup 86}Y-DOTA-Bn in mice bearing the SW1222 subcutaneous (s.c.) CRC xenograft model. Using optimized PRIT, therapeutic indices (TIs) for tumor radiation-absorbed dose of 73 (tumor/blood) and 12 (tumor/kidney) were achieved. Estimated absorbed doses (cGy/MBq) to tumor, blood, liver, spleen, and kidney for single-cycle PRIT were 65.8, 0.9 (TI 73), 6.3 (TI 10), 6.6 (TI 10), and 5.3 (TI 12), respectively. Two cycles of PRIT (66.6 or 111 MBq {sup 177}Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm{sup 3}) in nine of nine mice, with two mice alive without recurrence at >140 days. Tumor log kill in this model was estimated to be 2.1 - 3.0 based on time to 500-mm{sup 3} tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten {sup 86}Y-DOTA-Bn. We have developed anti-GPA33 PRIT as a triple-step theranostic strategy for preclinical detection, dosimetry, and safe targeted radiotherapy of established human colorectal mouse xenografts. (orig.)

  4. 51Cr-EDTA plasma clearance in severe renal failure determined by one plasma sample

    DEFF Research Database (Denmark)

    Kamper, A L; Nielsen, S L

    1989-01-01

    at zero-time was derived from injected dose and body surface area. This method might provide values 1.5 ml/min below or 0.8 ml/min above the established method of 51Cr-EDTA plasma clearance, which would be acceptable for clinical purposes. It is concluded that exact plasma clearance of 51Cr-EDTA in severe......Two hundred and thirty-four measurements of standard 51Cr-EDTA plasma clearance were made in 50 patients with severe chronic renal failure. Based on these data two calculation methods were attempted using one plasma sample drawn 24 h after injection of 51Cr-EDTA. One of the methods used the 'one...... sample clearance' formulas disregarding exact time of plasma sampling. This method might provide values 3.1 ml/min below or 2.9 ml/min above the established method of total 51Cr-EDTA plasma clearance, and would thus provide insufficient agreement. In the other method an estimate of plasma activity...

  5. (51Cr)EDTA intestinal permeability in children with cow's milk intolerance

    Energy Technology Data Exchange (ETDEWEB)

    Schrander, J.J.; Unsalan-Hooyen, R.W.; Forget, P.P.; Jansen, J. (Academic Hospital Maastricht (Netherlands))

    1990-02-01

    Making use of ({sup 51}Cr)EDTA as a permeability marker, we measured intestinal permeability in a group of 20 children with proven cow's milk intolerance (CMI), a group of 17 children with similar complaints where CMI was excluded (sick controls), and a group of 12 control children. ({sup 51}Cr)EDTA test results (mean +/- SD) were 6.85 +/- 3.64%, 3.42 +/- 0.94%, and 2.61 +/- 0.67% in the group with CMI, the sick control, and the control group, respectively. When compared to both control groups, patients with cow's milk intolerance (CMI) showed a significantly increased small bowel permeability. We conclude that the ({sup 51}Cr)EDTA test can be helpful for the diagnosis of cow's milk intolerance.

  6. Dosimetry and microdosimetry of {sup 188} Re-anti-CD20 and {sup 131} I-anti-CD20 for the treatment of No Hodgkin lymphomas; Dosimetria y microdosimetria del {sup 188} Re-anti-CD20 y {sup 131} I-anti-CD20 para el tratamiento de linfomas No Hodgkin

    Energy Technology Data Exchange (ETDEWEB)

    Torres G, E

    2007-07-01

    The purpose of this investigation was to prepare {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20 and to estimate the radiation absorbed dose at macro- and micro- level during a NHL treatment. The work was divided in 4 general objectives: 1) preparation of {sup 131}I-anti-CD20 and {sup 188}Re-anti-CD20, 2) application in patients to obtain biokinetic parameters and estimate the organ absorbed doses 3) estimation of the cellular dosimetry using the MIRD methodology and the MCNP4C2 code and 4) estimation of the cellular microdosimetry using the NOREC code. {sup 188}Re-anti-CD20 was prepared by a direct labelling method using sodium tartrate as a weak ligand. To evaluate the biological recognition a comparative study of the in vitro binding of {sup 188}Re-anti-CD20, {sup 125}I-anti-CD20 (positive control) and {sup 188}Re-anti-CEA (negative control) to normal B Iymphocytes was performed. Biodistribution studies in normal mice were accomplished to assess the in vivo Re-anti-CD20 complex stability. The binding of ' Re-anti-CD20 to cells was in the same range as '251-anti-CD20 (>80%) considered as the positive control. {sup 188}Re-anti-CD20 and '3'1-anti-CD20 prepared were administered in patients diagnosed with B cell NHL at the Centro Medico Siglo XXI (IMSS). The protocol was approved by the hospital's Medical Ethics Committee. AJI patients signed a consent form after receiving detailed information on the aims of the study. N data were the input for the OLINDA/EXM software to calculate the radiation absorbed dose to organs and whole body. Dosimetric studies indicate that after administration of 6.4 GBq and 4.87 to 8.75 GBq of '3'1-anti-CD20 and {sup 188}Re-anti-CD20 respectively, the absorbed dose to total body would be 0.75 Gy which corresponds to the recommended dose for NHL therapies. The calculated organ absorbed doses indicate that {sup 188}Re-anti-CD20 may be used in radioimmunotherapy without the risk of toxicity to red marrow or

  7. Patients with ovarian cancer have elevated (51)Cr-EDTA plasma clearance early post-operatively

    DEFF Research Database (Denmark)

    Nielsen, S S; Havsteen, H; Petersen, L K;

    2002-01-01

    Plasma clearance of (51)Cr-EDTA (Clp(EDTA)) is widely used to determine glomerular filtration rate prior to carboplatin based chemotherapy. We have observed that many patients with ovarian cancer have elevated Clp in the early post-operative phase compared to later phases. The purpose of this stu...

  8. 温敏型壳聚糖介入核素188Re内照射抗小鼠移植性肝癌(H22)%Invistagation of antitumor efffect of internal Irradiation of Interventional Radionuclide 188 Re in Thermosensitive Chitosan on Mouse Transplanted Tumor H22

    Institute of Scientific and Technical Information of China (English)

    董峰; 郭红云; 张永东; 梅澍

    2011-01-01

    Objectives To study the inhibitory activity of internal irradiation of interventional radionuclide 188 Re in thermosensitive chitosan on mouse transplanted tumor H22 (liver cancer).Method The tumor-bearing mice were divided into 7 groups randomly, including model control, 188Re(0.1mCi) group, 188Re-S(0.1mCi) group, 188Re + CS(0.1mCi)group, 188Re + CS (0.2mCi)group, 188Re-S + CS 0.1mCi)and188Re-S + CS(0.2mCi)group.The mice tumor was injected with corresponding reagent respectively, and the inhibitoy rate of tumor was observed after administrated.Results The growth of tumors in 188Re + CS group and 188Re-S + CS group was slowed.the tumor inhibitory rate reached the highest level after 6 days therapy, which respectively was 67.35% and 67.81%.Conclusions Internal irradiation of interventional radionuclide 188 Re in thermosensitive ehitosan had the effect of inhibitory mice liver cancer.%目的 研究温敏型壳聚糖(chitonsan CS)介入核素188Re内照射对小鼠移植性肝RW(H22)的抑制作用.方法 建立小鼠肝癌(H22)模型后随机分成7组,即模型对照组、.88Re(0.1mCi)组、188Re-S (0.1mCi)组、188Re +CS (0.1 mci)组、188Re + CS (0.2mCi)组、188Re+硫胶体+壳聚糖(188Re-S + CS 0.1 mCi)组和188Re-S + CS (0.2mCi )组.各组动物瘤内分别注射相应试药,测定肿瘤抑制率.结果 188Re + CS组和188Re-S + CS组肿瘤生长速度减慢,肿瘤生长延迟,肿瘤抑制率在治疗后6d最高,抑制率分别为67.35%和67.81%.结论 温敏型壳聚糖介入核素188Re内照射对小鼠肝癌(H22)具有一定的抑制作用.

  9. INTERNAL FRICTION OF 51CrV4 SHAFT INFLUENCED BY THERMO-MECHANICAL COUPLING

    Institute of Scientific and Technical Information of China (English)

    J. G(o)ken; M. Maikranz-Valentin; K. Steinhoff; T.S. Pavlova; T.V. Ivleva; I.S. Golovin

    2008-01-01

    The simultaneous influence of thermal and mechanical treatment was applied to produce a geometrically complex shaft from 51CrV4 steel leading to the formation of microstructures which were significantly different from each other. These microstructural differences were accompanied by a local change of mechanical properties in terms of hardness, electrical resistivity and especially internal friction. The Snoek-Koster peak was recognized and analyzed in the structure of this steel.

  10. Myeloablative radioimmunotherapy with {sup 188}Re-CD66mAb before stem cell transplantation. No increase of proinflammatory cytokine levels of TNF-{alpha}; Myeloablative Radioimmuntherapie mit {sup 188}Re-CD66mAb vor Stammzelltransplantation. Kein Anstieg proinflammatorischer Zytokinspiegel von TNF-{alpha}

    Energy Technology Data Exchange (ETDEWEB)

    Mutschler, J.; Reske, S.N. [Universitaetsklinik Ulm (Germany). Klinik fuer Nuklearmedizin; Steinbach, G. [Universitaetsklinik Ulm (Germany). Abt. Klinische Chemie; Bunjes, D. [Universitaetsklinik Ulm (Germany). Medizinische Klinik III; Buchmann, I. [Universitaetsklinik Heidelberg (Germany). Abt. fuer Nuklearmedizin

    2009-07-01

    Tumour necrosis factor-{alpha} (TNF-{alpha}) serum levels may increase due to intensive conditioning regimes with high-dose chemotherapy and total body irradiation (TBI) before stem cell transplantation. This increases the risk for developing acute graft versus host disease (aGvHD) after stem cell transplantation. In this prospective study we investigated the influence of radioimmunotherapy with {sup 188}Re-CD-66-mAb on changes on TNF-{alpha} serum levels. Patients, methods: In 18 patients we measured TNF-{alpha} before and up to 96 hours after radioimmunotherapy, in 2 patients in addition following TBI, in 9 patients also following chemotherapy. For measuring TNF-{alpha} we used an automated immunochemiluminescence assay (Immulite 1000 DPC Biermann, Bad Nauheim). The mean follow up period to record incidence of aGVHD was 100 days after stem cell transplantation. Compared to the basal levels before, the levels of TNF-{alpha} after conditioning with {sup 188}Re-CD-66-mAb did not increase significantly and remained in the physiological range. In contrast, these initial physiological cytokine levels increased and became pathological following 48 h after total body irradiation (13.2 {+-} 6.6 pg/ml) and chemotherapy (10.8 {+-} 15.7 pg/ml). In our study we found a low incidence of aGvHD (22.2%, n = 4/18). Conclusion: These results demonstrate that additional conditioning therapy with {sup 188}Re-CD-66-mAb does not increase proinflammatory cytokine levels of TNF-{alpha}. This finding may indicate that additive radioimmunotherapy may not be a significant factor for increasing the rate of conditioning- associated aGvHD. (orig.)

  11. Affinity of hydroxyapatite by radionuclides parent/child in {sup 188}Re/{sup 188}W generator for radiotherapy; Afinidad de la hidroxiapatita por los radionuclidos padre/hijo en el generador {sup 188}Re/{sup 188}W para radioterapia

    Energy Technology Data Exchange (ETDEWEB)

    Carrera D, A. A. [Universidad Autonoma de Zacatecas, Unidad Academica de Ciencias Quimicas, Campus Universitario Siglo XXI, Ejido La Escondida, Carretera a Guadalajara Km. 6 (Mexico); Badillo A, V. [Universidad Autonoma de Zacatecas, Unidad Academica de Estudios Nucleares, Calle Cipres No. 10, Fracc. La Penuela 98068, Zacatecas (Mexico); Badillo A, V. E.; Monroy G, F. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)], e-mail: ana_carrera7@hotmail.com

    2009-10-15

    To assess the feasibility of using apatites as matrices of {sup 188}W/{sup 188}Re generator is essential to obtain the distribution coefficients as much of parent radionuclide as child radionuclide in apatite, that is to say to know their affinity for the solid. It was selected the mineral species more representative as adsorbent, the hydroxyapatite Ca{sub 10} (PO{sub 4}){sub 6}(OH){sub 2} it is known for its great capacity of ions retention and by presenting a large affinity for anionic species in their surface. In this paper we use a synthetic hydroxyapatite marketed by Bio-Rad. This paper presents the preliminary results regarding the affinity of hydroxyapatite for the anionic species tungstates (WO{sub 4}{sup 2-}) and perrhenates (ReO{sub 4}{sup -} in EDTA, as background electrolyte expressed as distribution coefficients between two immiscible phases obtained with the help of radioactive tracers {sup 187}W and {sup 188}Re respectively. The retention measures of these ions, traces show that Bio-Gel hydroxyapatite presents moderate values of distribution coefficients for anionic species of W(Vi) in EDTA 0.01 mol/L that are in the range p H 5 to 6.5; the parent radionuclide of generator {sup 188}Re/{sup 188}W is fixed but not enough to consider it a good absorbent. By contrast, the fixation of perrhenate ions is virtually wiped as may be easily removed from a hydroxyapatite column packed with a saline solution. The influence of this saline solution in the removal of perrhenate ions is null practically. (Author)

  12. Calculus of spatial distribution of absorbed dose to cellular level by Monte Carlo simulation for a radio-labelled peptide with {sup 188}Re and with nuclear internalization : preliminary results; Calculo de la distribucion espacial de dosis absorbida a nivel celular por simulacion Monte Carlo para un peptido radiomarcado con {sup 188}Re y con internalizacion nuclear : resultados preliminares

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L. [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico); Santos C, C. L. [Universidad Autonoma del Estado de Mexico, Paseo Tollocan y Jesus Carranza, Toluca 50120, Estado de Mexico (Mexico)], e-mail: leticia.rojas@inin.gob.mx

    2009-10-15

    The {sup 188}Re is a radionuclide of radiation gamma emitter, useful in obtaining of gamma-graphic images, but it is also emitter of beta radiations and Auger electrons. A bio-molecule directed to a specific receptor of a cancer cell labeled with a emitter radionuclide of beta particles and Auger electrons, as the {sup 188}Re-Tat-Bombesin, it has the potential to be used in radiotherapy of molecular targets for its capacity to penetrate to cellular nucleus. In this system, the radiation dose is distributed in way located at microscopic levels in sub cellular specific places, where Auger emissions contributes of significant way in absorbed dose. The cellular dosimetry is realized in most of cases, using analytic or semi analytical methods, for example the cellular MIRD methodology. However, it is required to complement these calculations simulating the electrons transport and considering experimental bio kinetics data. Therefore, in this work preliminary results are presented of dosimetric calculation to sub cellular level for {sup 188}Re-Tat-Bombesin by Monte Carlo simulation, using the 2008 version of PENELOPE: PENEASY code. The spatial distribution of absorbed dose in membrane, cytoplasm and nucleus, was calculated with geometry of a cell of 10 {mu}m of diameter, a nucleus of 2 {mu}m of ratio and membrane of 0.2 {mu}m of thickness, considering elementary constitution for each cellular compartment proposal in literature. The total number of disintegrations at sub cellular level was evaluated integrating the activity in function of time starting from experimental bio kinetics data in mamma cancer cells MDA-MB231. The preliminary results show that 46.4% of total disintegrations for unit of captured activity by cell occurs in nucleus, 38.4% in membrane and 15.2% in cytoplasm. The due absorbed dose to Auger electrons for 1 Bq of {sup 188}Re located in cellular membrane were respectively of 1.32E-1 and 1.43E-1 Gy in cytoplasm and nucleus. (Author)

  13. Chromium oxide (51Cr2O3 used as biological marker was not absorbed by fish

    Directory of Open Access Journals (Sweden)

    G.Z. Sakita

    2015-06-01

    Full Text Available The aim of this study was to evaluate the rate absorption of radio-labeled chromium oxide (51Cr2O3, used as biological marker in nutrition studies with Nile tilapia Oreochromis niloticus. An experimental diet with approximately 58 µCi of specific activity of the element was encapsulated and fed daily to 35 adult Nile tilapia; a group of 35 fish was used as control feeding on a basal diet. At the beginning of the experiment five fish from each group were randomly selected and blood samples were drawn from control (BC and experimental fish (BE. Fish were then euthanized by anesthetic overdoses and samples of the liver tissue (LT, renal tissue (RT, stomach without content (S, intestine without content (I, gills tissue (GT, muscle tissue (fillet; MT, visceral fat (VF, content of the digestive tract (CTDE and water aquarium were collected from the experimental fish. The procedure was repeated daily for one week. Simple linear regressions were adjusted - days of collection vs. determination coefficients, and were established for statistical comparisons of the measured activity of 51Cr readings in sampled blood and tissues (logarithmic transformation for samples of the control and experimental fish. No differences (P>0.05 were detected between samples from BC fish and BE, RT, VF, MT and LT of treated fish, but samples of GT, I, S, CTDE and WA from the tanks holding fish which received the experimental diet differed from control (P<0.05. The experimental results indicate that the trivalent chromium in the form of 51Cr2O3 was not significantly absorbed by the gastrointestinal tract, gills or another possible route of absorption under these experimental conditions and with Nile tilapia. Therefore, this marker was shown to be inert and can be safely used in nutrition studies.

  14. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J.I.

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  15. Uptake studies of environmentally hazardous {sup 51}Cr in Mung beans

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, Anupam [Department of Botany, University of Calcutta, 35, Ballygunge Circular Road, Kolkata 700019 (India); Nayak, Dalia [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India); Chakrabortty, Dipanwita [Sikkim Manipal University, A 15, Paryavaran Complex, New Delhi 110030 (India); Lahiri, Susanta [Chemical Sciences Division, Saha Institute of Nuclear Physics, 1/AF Bidhannagar, Kolkata 700064 (India)], E-mail: susanta.lahiri@saha.ac.in

    2008-01-15

    Attempt has been made to study the accumulation behaviour of a common plant, Mung bean (Vigna radiata) towards Cr(III) and Cr(VI) to have an insight on the migration and bio-magnification of Cr. For this purpose healthy germinated Mung bean seeds were sown in the sand in the presence of Hoagland's nutrient solution containing measured amount of K{sub 2}{sup 51}Cr{sub 2}O{sub 7} and {sup 51}Cr(NO{sub 3}){sub 3}.9H{sub 2}O. Growth rate was also studied in the presence and absence of phosphate salts in the medium. It has been found that the transfer of chromium from soil to plant is significantly low (maximum 5% for both Cr(III) and Cr(VI)). Maximum accumulation of Cr occurs in the root with respect to the total chromium accumulation by the plant. Other parts of the Mung bean plant, e.g. cotyledons, shoot and leaves, show negligible accumulation. Therefore, the chance of direct intake of Cr through food as well as through the grazing animals to human body is less. - The chance of bio-magnification of Cr(III) or Cr(VI) to human body via direct or indirect intake of Mung bean is negligible.

  16. Intestinal permeability to (/sup 51/Cr)EDTA in children with Crohn's disease and celiac disease

    Energy Technology Data Exchange (ETDEWEB)

    Turck, D.; Ythier, H.; Maquet, E.; Deveaux, M.; Marchandise, X.; Farriaux, J.P.; Fontaine, G.

    1987-07-01

    (/sup 51/Cr)EDTA was used as a probe molecule to assess intestinal permeability in 7 healthy control adults, 11 control children, 17 children with Crohn's disease, and 6 children with untreated celiac disease. After subjects fasted overnight, 75 kBq/kg (= 2 microCi/kg) /sup 51/Cr-labeled EDTA was given by mouth; 24-h urinary excretion of (/sup 51/Cr)EDTA was measured and expressed as a percentage of the total oral dose. Mean and SD were as follows: control adults 1.47 +/- 0.62, control children 1.59 +/- 0.55, and patients with Crohn's disease or celiac disease 5.35 +/- 1.94. The difference between control children and patients was statistically significant (p less than 0.001). These results show that intestinal permeability to (/sup 51/Cr)EDTA is increased among children with active or inactive Crohn's disease affecting small bowel only or small bowel and colon, and with untreated celiac disease. The (/sup 51/Cr)EDTA permeability test could facilitate the decision to perform more extensive investigations in children suspected of small bowel disease who have atypical or poor clinical and biological symptomatology.

  17. A comparison of chromium sesquioxide and [51Cr]chromic chloride as inert markers in calcium balance studies.

    Science.gov (United States)

    Hesp, R; Williams, D; Rinsler, M; Reeve, J

    1979-07-01

    1. Chromium sesquioxide (Cr2O3; 1.5 g/day) and [51Cr]chromic chloride [51CrCl3 (0.3 muCi/day)] were compared as continuously administered non-absorbed markers for the correction of faecal recoveries in 14 calcium balance studies each lasting at least 18 days. 2. The mean recoveries of each, 98.4% for Cr2O3 and 101.9% for 51CrCl3, were not significantly different from 100%. 3. The two markers reduced the uncertainity in a typical 3 x 6 day calcium balance study to a similar extent (SD = 1.4 mmol/day for Cr2O3 and SD = 1.5 mmol/day for 51CrCl3. 4. 51CrCl3 is a convenient and satisfactorily alternative to Cr2O3 when the laboratory hazards associated with estimating the latter cannot easily be eliminated.

  18. Forces in Hard Turning of 51CrV4 with Wiper Cutting Tool

    Institute of Scientific and Technical Information of China (English)

    HE Xinfeng; WU Su; Hubert Kratz

    2006-01-01

    For precision machining, the hard turning process is becoming an important alternative to some of the existing grinding processes. This paper presents an analytical model for predicting cutting forces in hard turning of 51CrV4 with hardness of 68 HRC. The cutting tool used is made from cubic boron nitride (CBN) with a wiper cutting edge. Formulas for differential chip loads are derived for three different situations, depending on the radial depth of cut. The cutting forces are determined by integrating the differential cutting forces over the tool-workpiece engagement domain. For validation, cutting forces predicted by the model were compared with experimental measurements, and most of the results agree quite well.

  19. Preliminary results from the {sup 51}Cr neutrino source experiment in GALLEX

    Energy Technology Data Exchange (ETDEWEB)

    Hampel, W.; Heusser, G.; Kiko, J. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany)] [and others

    1996-09-01

    The GALLEX collaboration performed a second {sup 51}Cr neutrino source experiment during fall 1995. The full results from this second source experiment will not be available before the end of 1996. Meanwhile, we present a short description and preliminary results in this informal note. The (preliminary) value of the activity obtained form direct measurements has been found equal to (68.7 {+-}0.7) PBq (with 1-sigma error). This value, which is about 10% higher than the activity of the first source, was achieved by optimizing the irradiation conditions in the Silo{acute e} reactor and doing a longer irradiation of the enriched chromium. Preliminary results show that the ratio, R, of the radiochemically determined activity from {sup 71}Ge counting (57.1 {+-} PBq) to the directly measured activity is (0.83 {+-} 0.10). The combined value of R for the two source experiments is (0.92 {+-} 0.08).

  20. Bioaccumulation of 51Cr, 63Ni and 14C in Baltic Sea benthos.

    Science.gov (United States)

    Kumblad, L; Bradshaw, C; Gilek, M

    2005-03-01

    The Baltic Sea is a species-poor, semi-enclosed, brackish sea, whose sediments contain a wide range of contaminants, including sediment-associated metals and radionuclides. In this study, we have examined and compared bioaccumulation kinetics and assimilation efficiencies of sediment-associated (51)Cr, (63)Ni and (14)C in three key benthic invertebrates (the deposit-feeding Monoporeia affinis, the facultative deposit-feeding Macoma baltica, and the omnivorous Halicryptus spinulosus). Our results demonstrate that (i) all radionuclides were accumulated, (ii) the different radionuclides were accumulated to various extents, (iii) small changes in organic carbon concentration can influence the accumulation, and (iv) the degree of accumulation differed only slightly between species. These processes, together with sediment resuspension and bioturbation, may remobilise trace metals from the sediment to the water and to higher trophic levels, and therefore should be taken into account in exposure models and ERAs.

  1. Revisiting normal {sup 51}Cr-ethylenediaminetetraacetic acid clearance values in children

    Energy Technology Data Exchange (ETDEWEB)

    Piepsz, A.; Tondeur, M. [Department of Radioisotopes, CHU St Pierre, Brussels (Belgium); Ham, H. [Department of Nuclear Medicine, UZ Ghent, Ghent (Belgium)

    2006-12-15

    Normal {sup 51}Cr-ethylenediaminetetraacetic acid (EDTA) clearance values as a function of age were published a number of years ago. These values were based on data from children with a normal left to right ratio and a normal appearance on DMSA scintigraphy, despite the presence of an acute renal infection. At that time, the authors were unaware that hyperfiltration is a common phenomenon in patients with acute renal infection and that their normal values could have been significantly overestimated. The present work therefore aimed to re-appraise these normal values. In a first step, in order to verify the previous results, the same type of population was selected, namely patients with present or past urinary tract infection but normal images and a normal left to right ratio on DMSA scintigraphy. In a second step, the selection was based on patients who had had no recent urinary tract infection. In both series, a single blood sample method was used for the evaluation of {sup 51}Cr-EDTA clearance. In the first group of patients, the results obtained were almost identical to those previously published. In the second group of patients, the results were significantly lower: after 2 years of age, the mean GFR value was 104 ml/min/1.73 m{sup 2} (10th and 90th percentiles 81 and 135 ml/min/1.73 m{sup 2}, respectively), compared with 117 ml/min/1.73 m{sup 2} in the first group. The data of the second group are probably more representative of the true normal GFR values and can be applied to the entire paediatric population. (orig.)

  2. Study by Monte Carlo simulation of the absorbed dose in cells of breast cancer of the line MDA-MB231, due to sources of {sup 111}In, {sup 177}Lu and {sup 99m}Tc internalized in the nucleus. First results; Estudio por simulacion Monte Carlo de la dosis absorbida en celulas de cancer de seno de la linea MDA-MB231, debida a fuentes de {sup 11I}n, {sup 177}Lu y {sup 99m}Tc internalizadas en el nucleo. Primeros resultados

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L.; Perez A, M., E-mail: leticia.rojas@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2011-11-15

    The necessity to design innovative treatments and to diagnose the cancer early, has taken to investigate therapies at cellular and molecular level. The design of appropriate radio-molecules to these therapies makes necessary to characterize in way exhaustive radionuclides that they are of accessible production in our country and to study as distributing the dose at cellular level with bio-molecules glued them. In this context, was realized the present work. Using Monte Carlo simulation, the energy deposited in a geometric model of cells of breast cancer was obtained, MDA-MB231, due to different radionuclides. The energy deposited in the nucleus was evaluated, in the cytoplasm and in the membrane of the cell, using the simulation code Monte Carlo Penelope 2008. A punctual source was simulated in the center of the cell nucleus. In each case all the emissions of each radionuclide majors to 400 eV were simulated. The energies deposited by disintegration in the nucleus, cytoplasm, membrane of the cell and in a sphere of 2 cm surrounding the source (in eV) were: 4.30E3, 4.85E2, 1.07E2 and 3.29E4, correspondingly, for the {sup 111}In; 4.46E3, 3.76E3, 1.26E3 and 1.33E5 for the {sup 177}Lu and; 2.12E3, 2.58E2, 9.33E1 and 1.88E4 for the {sup 99m}Tc. We can conclude that if the union of these radionuclides happens to a compound that was internalized to the cell nucleus, the best for therapy at this level is the conjugate with the {sup 177}Lu, followed by that with {sup 111}In and in third place that with {sup 99m}Tc. (Author)

  3. 放射性核素188Re诱导人乳腺癌ER-75-30细胞的凋亡%Apoptosis of human breast cancer cell induced by radionuclide 188Re

    Institute of Scientific and Technical Information of China (English)

    邹保民; 段小艺; 胡国瑛

    2002-01-01

    目的研究放射性核素188铼(188Re)诱导乳腺癌 ER-75-30细胞凋亡及其与bcl-2和bax基因表达的关系. 方法应用光镜、电镜、流式细胞仪和免疫组化方法检测不同浓度 188Re作用于体外培养的乳腺癌ER-75-30细胞后,诱导细胞凋亡及bcl-2和bax基因表达情况。结果188Re以诱导乳腺癌ER-75-30细胞发生凋亡形态学变化,并且随着188Re浓度增大,凋谢亡率增加,bcl-2表达减弱,bax表达增强。结论188Re能诱导乳腺癌ER-75-30细胞凋谢亡且具有剂量和周期依赖性,bcl-2和bax基因在188Re诱导的细胞凋亡过程中具有重要作用。%AIM To study apoptosis of human breast cancer ER-75-30 cell induced by 188Re and expression of bcl-2 gene and bax gene. METHODS Light microscope, transmissional electron microscope, flow cytometer and immunohistochemical method were used to observed ER-75-30 cells apoptosis after expose to 188Re of different doses and expressing of bcl-2 and bax. RESULTS 188Re can induced ER-75-30 cell producing typical morphologic changes of apoptosis and with the rise of radiation dose, cell apoptosis rate increased, bcl-2 gene decreased and bax gene was enhanced. Cells were blocked in G2/M period. CONCLUSION Radionuclide 188Re can induce tumor cell apoptosis. This effect takes on dose-effect relation and cellcycle dependent. bcl-2 and bax gene play import part in the course.

  4. Physiopathology of blood platelets and development of platelets substitutes. Progress report, August 1, 1976--October 31, 1977. [/sup 51/Cr

    Energy Technology Data Exchange (ETDEWEB)

    Baldini, M G

    1977-07-31

    Progress is reported on the following research projects: the effect of estrogen on platelet aggregability and thrombus formation; the antithrombotic effect of platelet inhibiting agents in a bench model of artificial kidney; the arrest of hemorrhage in severely alloimmunized thrombocytopenic patients; and in vivo elution of /sup 51/Cr from labeled platelets induced by antibody. (HLW)

  5. Comparison between 125IUdR and 51Cr as cell labels in investigations of tumor cell migration

    DEFF Research Database (Denmark)

    Basse, P; Hokland, P; Hokland, M

    1991-01-01

    YAC-1 tumor cells double-labeled with Na2[51Cr]O4 [51Cr] and [125I]iododeoxyuridine [125IUdR] were injected intravenously into Balb/c mice in order to investigate their migration and fate 0-4 h after the injection. Whereas the clearance of tumor cells from the lung tissue was similar as judged...... in overestimation of the number of viable tumor cells in these organs. Moreover, a marked spontaneous release (greater than 10% after 12 h) makes 51Cr less suitable as a cell label than 125IUdR. On the other hand, we found that the release of 125I from dead cells in vivo depends at least partially on host factors...... such as macrophages. Consequently, caution must be exerted when tumor cell migration is investigated in animals treated with drugs that might affect the reticuloendothelial system. We conclude that 125IUdR is superior to 51Cr as a cell label for investigation of tumor cell migration in vivo, even though some doubt...

  6. Conventional measurements of GFR using {sup 51}Cr-EDTA overestimate true renal clearance by 10 percent

    Energy Technology Data Exchange (ETDEWEB)

    Moore, Amelia E.B.; Park-Holohan, So-Jin; Blake, Glen M.; Fogelman, Ignac [Department of Nuclear Medicine, Guy' s Hospital, St Thomas Street, London, SE1 9RT (United Kingdom)

    2003-01-01

    It is widely believed that measurement of the area under the plasma clearance curve (AUC) following a single intravenous injection of chromium-51 labelled ethylene diamine tetra-acetic acid ({sup 51}Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that {sup 51}Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of {sup 51}Cr-EDTA plasma clearance contributing to the AUC measurement of GFR. Seventy healthy postmenopausal women (mean age 60 years, range 45-79 years) were injected with 3 MBq {sup 51}Cr-EDTA and 0.25 MBq iodine-125 labelled human serum albumin and 11 blood samples taken between 0 and 4 h through an indwelling venous cannula. For the first 21 subjects, two complete urine collections were made 0-2 h and 2-4 h after injection, and for the final 49 patients, four 1-h urine collections were made. The mean {sup 51}Cr-EDTA total plasma clearance was 84 ml/min (range 50-132 ml/min). The mean ratio (SEM) of urine to total clearance determined from the cumulative 1-, 2-, 3- and 4-h data was 0.903 (0.018), 0.891 (0.013), 0.898 (0.011) and 0.899 (0.010) respectively and remained constant despite the mean urine concentration decreasing from 122% to 15%/litre during this period. A least squares fit to data from the 238 individual urine collections was used to determine the fraction of the total plasma clearance attributable to renal clearance, {alpha}{sub 0}, and the residual urine volume, {delta}V. The results were {alpha}{sub 0}=0.910 (95% CI: 0.889-0.932) and {delta}V=14 ml (95% CI: -4 to +34 ml). The overestimation of the true renal clearance of {sup 51}Cr-EDTA by the AUC method is believed to be due to the failure of the plasma clearance curve to reach the true terminal exponential by 2 h after injection as usually assumed. As a result, conventional measurements of GFR using {sup 51}Cr-EDTA overestimate the true renal clearance of tracer

  7. Bioenergetics of three aquatic insects determined by radioisotopic analyses. [/sup 51/Cr and /sup 14/C tracer techniques

    Energy Technology Data Exchange (ETDEWEB)

    McCullough, D.A.

    1975-08-01

    The bioenergetics of Simulium spp. and Cheumatopsyche analis from Rattlesnake Springs and Snively Creek, respectively, Benton County, Washington and Tricorthodes minutus from Deep Creek, Oneida County, Idaho were studied using a variety of techniques. Ingestion rates were measured using food sources (diatoms, finely ground watercress, bacteria, and blue-green algae) labelled with /sup 51/Cr and /sup 14/C. Theoretical ingestion rates were calculated from analyses of gut weights and digestion times. Assimilation efficiencies (AE) were determined using the /sup 14/C and dual-label (/sup 51/Cr, /sup 14/C) methods and the ash-ratio technique. The dual-label method provided reliable results when leaching of isotopes from food and feces were not significant. Provided the /sup 51/Cr activity density of food is sufficient, the time required for digestion can also be more accurately determined with /sup 51/Cr than with /sup 14/C. The ash-ratio method provided a wide range of AE values and is not as reliable as the dual-label method because mineral assimilationis unpredictable. Assimilation rates were derived for these animals using the ingestion rate and AE, by several methods employing /sup 14/C uptake curves, and by differences in /sup 51/Cr- and /sup 14/C-derived accumulation values. Methods used to measure other energy budget components are also given. A system was developed for combusting biological samples containing /sup 14/C and determining cpm /sup 14/C and total carbon from a single sample. This method employs Van Slyke wet oxidation, forced circulation and scrubbing of the gases of combustion, and collection of CO/sub 2/ in ethanolamine. Radioactivity in this system was determined by scintillation counting and total carbon by a gravimetric precipitation method. (auth)

  8. The use of 99mTc-HYNIC-TOC and 18F-FDG PET/CT in the evaluation of duodenal neuroendocrine tumor with atypical and extensive metastasis responding dramatically to a single fraction of PRRT with 177Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit

    2014-12-01

    This report describes a case of extensive diffuse bone marrow involvement with bilateral breast metastases from duodenal neuroendocrine tumor giving rise to a superscan-like appearance on somatostatin receptor-targeted (99m)Tc-hydrazinonicotinamide-TOC scintigraphy. The metastatic lesions demonstrated partial concordance with (18)F-FDG PET/CT findings, signifying varying tumor biology and heterogeneity among metastatic lesions in the same individual, as illustrated with a dual-tracer approach. There was a dramatic symptomatic and biochemical response and better health-related quality of life with a single fraction of peptide receptor radionuclide therapy with (177)Lu-DOTATATE, and radiologically there was stable disease at that point.

  9. The Granzyme B ELISPOT assay: an alternative to the 51Cr-release assay for monitoring cell-mediated cytotoxicity

    Directory of Open Access Journals (Sweden)

    Baseler Michael

    2003-12-01

    Full Text Available Abstract Background The interferon-γ (IFN-γ ELISPOT assay is one of the most useful techniques for immunological monitoring of cancer vaccine trials and has gained increased application as a measure of specific T cell activation. However, it does not assess cell-mediated cytotoxicity directly as IFN-γ secretion is not limited to only cytolytic cells. Granzyme B (GrB is a key mediator of target cell death via the granule-mediated pathway. Therefore, the release of GrB by cytolytic lymphocytes upon effector-target interaction may be a more specific indicator of CTL and NK cytotoxic ability than IFN-γ secretion. Methods We assessed whether the GrB ELISPOT assay is a viable alternative to the 51Cr-release and IFN-γ ELISPOT assays for measuring antigen-specific CTL cytotoxicity. Direct comparisons between the three assays were made using human CTL cell lines (αEN-EBV and αJY and an in vitro stimulated anti-Flu matrix peptide (FMP-specific CTL. Results When the GrB ELISPOT was directly compared to the IFN-γ ELISPOT and 51Cr-release assays, excellent cross-correlation between all three assays was shown. However, measurable IFN-γ secretion in the ELISPOT assay was observed only after 1 hour of incubation and cytotoxicity assessed via the 51Cr-release assay after 4 hours, whereas GrB secretion was detectable within 10 min of effector-target contact with significant secretion observed after 1 h. Titration studies demonstrated a strong correlation between the number of effector cells and GrB spots per well. Irrelevant targets or antigens did not induce significant GrB secretion. Additionally, GrB secretion was abrogated when CTL cultures were depleted of CD8+ cells. Conclusion Our findings demonstrate that the GrB ELISPOT assay is a superior alternative to the 51Cr-release assay since it is significantly more sensitive and provides an estimation of cytotoxic effector cell frequency. Additionally, unlike the IFN-γ ELISPOT assay, the GrB ELISPOT

  10. Study of the reaction between {sup 51}CrO{sub 3} and concentrated nitric acid by radio chromatographic methods; Estudo da reacao entre {sup 51}CrO{sub 3} e acido nitrico concentrado por metodos radiocromatograficos

    Energy Technology Data Exchange (ETDEWEB)

    Pezzin, Sergio H. [Univesidade do Estado de Santa Catarina (UDESC), Joinville, SC (Brazil). Centro de Ciencias Tecnologicas; Collins, Carol H.; Collins, Kenneth E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica

    2000-07-01

    The objective of the present work is to verify the reduction of CrO{sub 3} in concentrated nitric acid, using {sup 51}Cr as a tracer. For the study, {sup 51}CrO{sub 3} (ca. 200,000 cpm/mg) was added to 65% HNO{sub 3} and maintained under agitation at 20 deg C for specified time periods. Aliquots (100 {mu}) were analyzed by open column cation (AG50Wx8, 100-200 mesh, Na{sup +} form) chromatography, either immediately or after dilution to approximately pH 2 and storage for specified time periods. The separations, which were made by stepwise elution using HClO{sub 4} and Ca(ClO{sub 4}){sub 2} solutions as effluents with fraction collection, followed by counting with a NaI(Tl) detector and a single channel analyzer. It was verified that ca. 3.5% of Cr(III) is obtained after 15 min of reaction. The major reaction product is hexaaquo chromium(III), with minor concentrations of mononitrate penta-aquochromium(III), [Cr(H{sub 2}O){sub 5}NO{sub 3}]{sup 2+}, a product which undergoes watering at pH 2 to produce, after 360 h, [Cr(H{sub 2}O){sub 6}]{sup 3+}. (author)

  11. Evaluation of S-values and dose distributions for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re in seven lobes of the rat liver

    Energy Technology Data Exchange (ETDEWEB)

    Xie Tianwu; Liu Qian; Zaidi, Habib [Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074 (China) and Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074 (China); Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan 430074 (China); Key Laboratory of Biomedical Photonics of Ministry of Education, Huazhong University of Science and Technology, Wuhan 430074 (China) and Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Division of Nuclear Medicine and Molecular Imaging, Geneva University Hospital, CH-1211 Geneva (Switzerland); Geneva Neuroscience Center, Geneva University, CH-1211 Geneva (Switzerland) and Department of Nuclear Medicine and Molecular Imaging, University Medical Center Gronigen, University of Groningen, 9700 RB Groningen (Netherlands)

    2012-03-15

    Purpose: Rats have been widely used in radionuclide therapy research for the treatment of hepatocellular carcinoma (HCC). This has created the need to assess rat liver absorbed radiation dose. In most dose estimation studies, the rat liver is considered as a homogeneous integrated target organ with a tissue composition assumed to be similar to that of human liver tissue. However, the rat liver is composed of several lobes having different anatomical and chemical characteristics. To assess the overall impact on rat liver dose calculation, the authors use a new voxel-based rat model with identified suborgan regions of the liver. Methods: The liver in the original cryosectional color images was manually segmented into seven individual lobes and subsequently integrated into a voxel-based computational rat model. Photon and electron particle transport was simulated using the MCNPX Monte Carlo code to calculate absorbed fractions and S-values for {sup 90}Y, {sup 131}I, {sup 166}Ho, and {sup 188}Re for the seven liver lobes. The effect of chemical composition on organ-specific absorbed dose was investigated by changing the chemical composition of the voxel filling liver material. Radionuclide-specific absorbed doses at the voxel level were further assessed for a small spherical hepatic tumor. Results: The self-absorbed dose for different liver lobes varied depending on their respective masses. A maximum difference of 3.5% was observed for the liver self-absorbed fraction between rat and human tissues for photon energies below 100 keV. {sup 166}Ho and {sup 188}Re produce a uniformly distributed high dose in the tumor and relatively low absorbed dose for surrounding tissues. Conclusions: The authors evaluated rat liver radiation doses from various radionuclides used in HCC treatments using a realistic computational rat model. This work contributes to a better understanding of all aspects influencing radiation transport in organ-specific radiation dose evaluation for

  12. Use of Monte Carlo simulations with a realistic rat phantom for examining the correlation between hematopoietic system response and red marrow absorbed dose in Brown Norway rats undergoing radionuclide therapy with {sup 177}Lu- and {sup 90}Y-BR96 mAbs

    Energy Technology Data Exchange (ETDEWEB)

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders [Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden); Department of Oncology, Clinical Sciences, Lund University, Lund (Sweden); Department of Medical Radiation Physics, Clinical Sciences, Lund University, Lund (Sweden)

    2012-07-15

    Purpose: Biokinetic and dosimetry studies in laboratory animals often precede clinical radionuclide therapies in humans. A reliable evaluation of therapeutic efficacy is essential and should be based on accurate dosimetry data from a realistic dosimetry model. The aim of this study was to develop an anatomically realistic dosimetry model for Brown Norway rats to calculate S factors for use in evaluating correlations between absorbed dose and biological effects in a preclinical therapy study. Methods: A realistic rat phantom (Roby) was used, which has some flexibility that allows for a redefinition of organ sizes. The phantom was modified to represent the anatomic geometry of a Brown Norway rat, which was used for Monte Carlo calculations of S factors. Kinetic data for radiolabeled BR96 monoclonal antibodies were used to calculate the absorbed dose. Biological data were gathered from an activity escalation study with {sup 90}Y- and {sup 177}Lu-labeled BR96 monoclonal antibodies, in which blood cell counts and bodyweight were examined up to 2 months follow-up after injection. Reductions in white blood cell and platelet counts and declines in bodyweight were quantified by four methods and compared to the calculated absorbed dose to the bone marrow or the total body. Results: A red marrow absorbed dose-dependent effect on hematological parameters was observed, which could be evaluated by a decrease in blood cell counts. The absorbed dose to the bone marrow, corresponding to the maximal tolerable activity that could safely be administered, was determined to 8.3 Gy for {sup 177}Lu and 12.5 Gy for {sup 90}Y. Conclusions: There was a clear correlation between the hematological effects, quantified with some of the studied parameters, and the calculated red marrow absorbed doses. The decline in body weight was stronger correlated to the total body absorbed dose, rather than the red marrow absorbed dose. Finally, when considering a constant activity concentration, the phantom

  13. Mannitol clearance for the determination of glomerular filtration rate-a validation against clearance of (51) Cr-EDTA.

    Science.gov (United States)

    Kiss, Katalin; Molnár, Miklós; Söndergaard, Sören; Molnár, Gyula; Ricksten, Sven-Erik

    2016-06-03

    We studied the agreement between plasma clearance of mannitol and the reference method, plasma clearance of (51) Cr-EDTA in outpatients with normal to moderately impaired renal function. Forty-one patients with a serum creatinine clearance was measured with the standard bolus injection technique and glomerular filtration rate (GFR) was calculated by the single-sample method described by Jacobsson. Mannitol, 0·25 g kg(-1) body weight (150 mg ml(-1) ), was infused for 4-14 min and blood samples taken at 1-, 2-, 3- and 4-h (n = 24) or 2-, 3-, 3·5- and 4-h after infusion (n = 17). Mannitol in serum was measured by an enzymatic method. Plasma clearance for mannitol and its apparent volume of distribution (Vd) were calculated according to Brøchner-Mortensen. Mean plasma clearance (±SD) for (51) Cr-EDTA was 59·7 ± 18·8 ml min(-1) . The mean plasma clearance for mannitol ranged between 57·0 ± 20·1 and 61·1 ± 16·7 ml min(-1) and Vd was 21·3 ± 6·2% per kg b.w. The between-method bias ranged between -0·23 and 2·73 ml min(-1) , the percentage error between 26·7 and 39·5% and the limits of agreement between -14·3/17·2 and -25·3/19·9 ml min(-1) . The best agreement was seen when three- or four-sample measurements of plasma mannitol were obtained and when sampling started 60 min after injection. Furthermore, accuracy of plasma clearance determinations was 88-96% (P30) and 41-63% (P10) and was highest when three- or four-sample measurements of plasma mannitol were obtained, including the first hour after the bolus dose. We conclude that there is a good agreement between plasma clearances of mannitol and (51) Cr-EDTA for the assessment of GFR.

  14. The speciation of products from the reaction of {sup 51} Cr(VI) with mineral acids by high efficiency liquid chromatography; Especiacao dos produtos da reacao entre {sup 51} Cr(VI) e acidos minerais por cromatografia liquida de alta eficiencia

    Energy Technology Data Exchange (ETDEWEB)

    Pezzin, Sergio H.; Collins, Carol H.; Collins, Kenneth E. [Universidade Estadual de Campinas, SP (Brazil). Inst. de Quimica; Archundia, Cielita [Universidad Nacional Autonoma de Mexico, Mexico DF (Mexico). Inst. de Ciencias Nucleares

    1996-07-01

    The speciation of the products from the reaction of {sup 51} Cr(VI) with concentrated acids (HClO{sub 4}, HCl e HF) was carried out by ion chromatography. The separation was made on a Partisil SCX (10 {mu}m) column, using HClO{sub 4} and Ca(ClO{sub 4}){sub 2} solutions as eluents. The eluates were measured by {gamma}-counting. The results for the reaction (1h) of carrier-free {sup 51} Cr(VI) with HCl show that 96.4% from the {sup 51} Cr is not retained on the column (anionic and/or neutral species). A similar result (92.7% not retained) is observed in a Cr(VI)-HF system. However, for the reaction with HClO{sub 4}, 82% of the {sup 51} Cr was observed as a +3 species and only 5.9% as anionic and/or neutral species. (author)

  15. Gamma-variate plasma clearance versus urinary plasma clearance of (51) Cr-EDTA in patients with cirrhosis with and without fluid retention

    DEFF Research Database (Denmark)

    Fuglsang, Stefan; Henriksen, Ulrik L; Hansen, Hanne Boskov

    2016-01-01

    In patients with fluid retention, the plasma clearance of (51) Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of (51) Cr......-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of (51) Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from...... the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu = ΔCl) was mean -0...

  16. Comparative gastrointestinal blood loss associated with placebo, aspirin, and nabumetone as assessed by radiochromium (/sup 51/Cr)

    Energy Technology Data Exchange (ETDEWEB)

    Lussier, A.; Davis, A.; Lussier, Y.; Lebel, E.

    1989-03-01

    Nabumetone differs from most other nonsteroidal anti-inflammatory drugs. It is presented to the gut as a nonacidic prodrug, and is metabolized to its active form after absorption. Studies in animals and humans suggest it is less irritating to the gastrointestinal mucosa. This study compared the gastrointestinal microbleeding induced by nabumetone to aspirin (acetylsalicylic acid, ASA), and placebo in a double blind parallel study using chromium /sup 51/Cr labelled red cells to quantitate fecal blood loss (FBL) in healthy volunteers. Thirty subjects were randomized to treatment with nabumetone (2000 mg), ASA (3.6 g) or placebo for 21 days following a 7 day placebo period. Six subjects served as untreated controls. FBL in nabumetone treated subjects was not significantly different to placebo or untreated subjects. In contrast, ASA-treated subjects exhibited significantly increased FBL than the other 3 groups (P less than .0001).

  17. Over-estimation of glomerular filtration rate by single injection [51Cr]EDTA plasma clearance determination in patients with ascites

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Brøchner-Mortensen, J; Malchow-Møller, A;

    1980-01-01

    The total plasma (Clt) and the renal plasma (Clr) clearances of [51Cr]EDTA were determined simultaneously in nine patients with ascites due to liver cirrhosis. Clt (mean 78 ml/min, range 34-115 ml/min) was significantly higher than Clr (mean 52 ml/min, range 13-96 ml/min, P .... To assess glomerular filtration rate in presence of ascites, the renal plasma clearance of [51Cr]EDTA should be used instead of the total plasma clearance....

  18. Validation of calculated eGFR compared with 51Cr-EDTA clearance on a patient population from northern Jutland in Denmark

    DEFF Research Database (Denmark)

    Nielsen, Nikolaj Schandorph

    I mange år har man anvendt patienters plasma-creatinin niveau i blodet som et estimat for nyrefunktionen. I september 2010 blev der i Aalborg indført eGFR som etstimat på nyrefunktion ud fra plasma-creatinin. Det er kendt at GFR bestemt ved 51Cr-EDTA clearence er det bedste bud på patienters...... nyrefunktion, og derfor undersøges validiteten af eGFR i forhold til GFR bestemt ved 51Cr-EDTA clearence....

  19. Arterio-venous concentration difference of [51Cr]EDTA after a single injection in man. Significance of renal function and local blood flow

    DEFF Research Database (Denmark)

    Rehling, M; Hyldstrup, Lars; Henriksen, Jens Henrik

    1989-01-01

    The present investigation was undertaken in order to study (1) the difference in arterial (Ca) and venous (Cv) concentration of [51Cr]EDTA (ethylenediaminetetraacetate) after a single intravenous injection, (2) the impact of different physiological variables on this difference, and (3) the error...

  20. Estimating GFR in children with 99mTc-DTPA renography: a comparison with single-sample 51Cr-EDTA clearance

    DEFF Research Database (Denmark)

    Gutte, Henrik; Møller, Michael L; Pfeifer, Andreas K

    2010-01-01

    Glomerular filtration rate (GFR) measurement by (51)Cr-ethylenediaminetetraacetic acid (EDTA) and blood sampling in children is usually cumbersome for the patient, parents and laboratory technicians. We have previously developed a method accurately estimating GFR in adults. The aim of the present...

  1. Labeling of NGR Peptide With 188Re and Its Biodistribution and SPECT Imaging in Tumor-bearing Nude Mice%NGR短肽的188Re标记及其在荷瘤裸鼠体内的生物分布和SPECT显像

    Institute of Scientific and Technical Information of China (English)

    锁耀宇; 杨卫东; 马晓伟; 汪静

    2011-01-01

    采用188Re标记含有天冬酰胺、甘氨酸、精氨酸(Asn-Gly-Arg,NGR)序列的肿瘤血管靶向性短肽,得到188Re-NGR,观察了188Re-NGR在荷HepG2肝癌细胞严重联合免疫缺陷(Severe Combined Immunodeficiency,SCID)裸鼠肿瘤模型中的生物分布,并对其进行了SPECT显像.结果显示,188Re-NGR的标记率>85%,放化纯度>90%.188Re-NGR在肿瘤模型鼠体内的生物分布显示,注射188Re-NGR后12 h,肿瘤放射性摄取达最高,为(4.62±0.71)%ID/g,24 h时仍有(2.01±0.38)%ID/g,说明标记物在肿瘤内停留时间较长;竞争性抑制组中,12 h肿瘤放射性摄取为(1.43±0.61)%ID/g,明显低于实验组.肿瘤与肌肉组织的放射性摄取比(T/NT)12 h为4.76.注射后1 h肿瘤可显像,4~8 h显像逐渐清晰,12 h时更为清晰.以上结果提示,188Re-NGR具有良好的肿瘤血管靶向性.%To evaluate its radiochemical characteristics, biodistribution and imaging for nude mice bearing HepG2, 188Re-NGR was prepared directly with 2-mercapto-ethanol as reductant and sodium gluconate as middle ligand. The labeling yield of 188 Re-NGR was more than 85%, and the radiochemical purity (RCP) was more than 90%. In vivo, 188Re-NGR can specifically bind with tumor. The tumor uptake was (2.84±0.51)%ID/g at 1 h after injection, the uptake was(4. 62±0. 71)%ID/g at 12 h and remains (2.01±0.38)%ID/g for 24 h, the contrl group was (1.43±0.61)%ID/g. The ratio of tumor to muscle was 4.76 at 12 h. The xenografted tumor became visible at 1 h and was the most clearly at 12 h. The results showed that NGR had the function of good targeting.

  2. Total plasma clearance versus urinary plasma clearance of (51)Cr-EDTA in patients with cirrhosis with and without fluid retention

    DEFF Research Database (Denmark)

    Henriksen, Ulrik Lütken; Hansen, Hanne B; Ring-Larsen, Helmer

    2015-01-01

    Abstract Background and aim. In patients with fluid retention, the total plasma clearance of (51)Cr-EDTA (ClP) may overestimate the glomerular filtration rate (GFR). The present study was therefore undertaken in order to compare ClP with the urinary plasma clearance of (51)Cr-EDTA (ClU) in patients...... with cirrhosis with and without fluid retention. Material and methods. A total of 136 patients with cirrhosis (24 without fluid retention, 112 with ascites) received a quantitative intravenous injection of (51)Cr-EDTA followed by plasma and quantitative urinary samples for 5 hours. ClP was determined from...... the injected dose relative to the plasma concentration-time area, extrapolated to infinity. ClU was determined as urinary excretion relative to the plasma concentration-time area up to voiding. Results. In patients without fluid retention, the difference between ClP and ClU (ClP - ClU = ClΔ) was mean 4.5 m...

  3. Glomerular filtration rate measured by {sup 51}Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Chaves, Anna Alice Rolim; Buchpiguel, Carlos Alberto; Praxedes, Jose Nery; Bortolotto, Luiz Aparecido; Sapienza, Marcelo Tatit, E-mail: annaalice100@yahoo.com.b [Universidade de Sao Paulo (USP), SP (Brazil). Faculdade de Medicina. Dept. de Neurologia

    2010-07-01

    Introduction: renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid ({sup 51}Cr-EDTA) could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using {sup 51}Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. Methods: this prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21) and without renal artery stenosis, (n=20). In vitro glomerular filtration rate analysis ({sup 51}Cr-EDTA) and {sup 99m}Tc-DMSA scintigraphy were performed before and after captopril administration in all patients. Results: the mean baseline glomerular filtration rate was 48.6+-21.8 ml/kg/1.73 m{sup 2} in the group with renal artery stenosis, which was significantly lower than the GFR of 65.1+-28.7 ml/kg/1.73m{sup 2} in the group without renal artery stenosis (p=0.04). Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6+-14.8 ml/kg/1.73m{sup 2}, p=0.001) and an insignificant change in the group without RAS (to 62.2+-23.6 ml/kg/1.73m{sup 2}, p=0.68). Scintigraphy with technetium-99m dimercapto

  4. Magnetic thermal hysteresis due to paramagnetic-antiferromagnetic transition in Fe-24.4Mn-5.9Si-5.1Cr alloy

    Directory of Open Access Journals (Sweden)

    L. Wang

    2013-08-01

    Full Text Available Magnetic thermal hysteresis (MTH associated with a paramagnetic (PM-antiferromagnetic (AFM phase transition was found in an Fe-24.4Mn-5.9Si-5.1Cr shape-memory alloy. Aside from the magnetic field (H, the driving rate (v can also tune the critical temperature of the magnetic transition and cause an increase in MTH. The magnetic phase diagram obtained is discussed. The equation for MTH was deduced based on the Landau model for a PM-AFM transition that includes H and v dependence, which gives a reasonable account of the experimental results.

  5. Glomerular filtration rate measured by 51Cr-EDTA clearance: evaluation of captopril-induced changes in hypertensive patients with and without renal artery stenosis

    Directory of Open Access Journals (Sweden)

    Anna Alice Rolim Chaves

    2010-01-01

    Full Text Available INTRODUCTION: Renal artery stenosis can lead to renovascular hypertension; however, the detection of stenosis alone does not guarantee the presence of renovascular hypertension. Renovascular hypertension depends on activation of the renin-angiotensin system, which can be detected by functional tests such as captopril renal scintigraphy. A method that allows direct measurement of the baseline and post-captopril glomerular filtration rate using chromium-51 labeled ethylenediamine tetraacetic acid (51Cr-EDTA could add valuable information to the investigation of hypertensive patients with renal artery stenosis. The purposes of this study were to create a protocol to measure the baseline and post-captopril glomerular filtration rate using 51Cr-EDTA, and to verify whether changes in the glomerular filtration rate permit differentiation between hypertensive patients with and without renal artery stenosis. METHODS: This prospective study included 41 consecutive patients with poorly controlled severe hypertension. All patients had undergone a radiological investigation of renal artery stenosis within the month prior to their inclusion. The patients were divided into two groups: patients with (n=21 and without renal artery stenosis, (n=20. In vitro glomerular filtration rate analysis (51Cr-EDTA and 99mTc-DMSA scintigraphy were performed before and after captopril administration in all patients. RESULTS: The mean baseline glomerular filtration rate was 48.6±21.8 ml/kg/1.73 m² in the group wuth renal artery stenosis, which was significantly lower than the GFR of 65.1±28.7 ml/kg/1.73m² in the group without renal artery stenosis (p=0.04. Captopril induced a significant reduction of the glomerular filtration rate in the group with renal artery stenosis (to 32.6±14.8 ml/kg/1.73m², p=0.001 and an insignificant change in the group without RAS (to 62.2±23.6 ml/kg/1.73m², p=0.68. Scintigraphy with technetium-99m dimercapto-succinic acid (DMSA did not show

  6. Arterio-venous concentration difference of [51Cr]EDTA after a single injection in man. Significance of renal function and local blood flow

    DEFF Research Database (Denmark)

    Rehling, M; Hyldstrup, L; Henriksen, Jens Henrik Sahl

    1989-01-01

    The present investigation was undertaken in order to study (1) the difference in arterial (Ca) and venous (Cv) concentration of [51Cr]EDTA (ethylenediaminetetraacetate) after a single intravenous injection, (2) the impact of different physiological variables on this difference, and (3) the error......, and 180-300 min post-injection (p.i.) Cv was 5.9% higher than Ca (range 0.5-13.9%, P less than 0.001). The more reduced renal function, the smaller was the concentration difference. The areas under the arterial and the venous plasma concentration curves did not differ significantly at either 0-infinity...... or 0-300 min p.i. whereas the venous area 0-100 min p.i. underestimated the arterial area in the same period by 4.1% (P less than 0.05). In a computer simulation model, variation in the forearm capillary permeability-surface area product did not have any significant influence on the Cv-Ca difference...

  7. Nanocrystallization and martensitic transformation in Fe-23.4Mn-6.5Si-5.1Cr (wt.%) alloy by surface mechanical attrition treatment

    Energy Technology Data Exchange (ETDEWEB)

    Wen Chunsheng; Li Wei [School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China); Rong Yonghua [School of Materials Science and Engineering, Shanghai Jiao Tong University, Shanghai 200030 (China)], E-mail: yhrong@sjtu.edu.cn

    2008-05-25

    Nanocrystalline grains can be obtained in the surface layer of an Fe-23.4Mn-6.5Si-5.1Cr (wt.%) alloy with low stacking-fault energy through surface mechanical attrition treatment, accompanying three kinds of strain-induced martensitic transformations. The microstructure of the surface layer was investigated using optical microscopy, X-ray diffraction and transmission electron microscopy. The results indicate the majority of {alpha} martensites can be formed directly from the original matrix ({gamma}, fcc), instead of forming at intersections of strain-induced {epsilon} martensites in {gamma} matrix grains. The nanocrystallization of grains has three approaches: both the intersection of strain-induced {epsilon}(hcp) martensites and the formation of strain-induced {alpha}(bcc) martensites from austenite lead to refinement of austenite grains, and the martensitic transformation from {epsilon}(hcp) to {alpha}(bcc) makes the grain sizes of the product {alpha}(bcc) smaller than those of {epsilon}(hcp). The strain-induced {alpha}(bcc) martensites formed from both austenite matrix and {epsilon}(hcp) martensites undergo evolution from dislocation tangles, low angle grain boundaries to large angle grain boundaries.

  8. Absolute 24 h quantification of 99Tcm-DMSA uptake in patients with severely reduced kidney function: a comparison with 51Cr-EDTA clearance.

    Science.gov (United States)

    van de Wiele, C; van den Eeckhaut, A; Verweire, W; van Haelst, J P; Versijpt, J; Dierckx, R A

    1999-09-01

    The aim of this study was to determine whether absolute 24 h DMSA uptake measurements (%DMSA) correlate well with 51Cr-EDTA clearance measurements in patients with severely reduced kidney function (SRKF). Between 1990 and 1997, 55 of 482 patients who underwent EDTA clearance measurements also underwent %DMSA within 1 week. Of these, 31 were women and 24 were men (mean age 60 years; range 19-77 years). EDTA clearance was determined using the slope-intercept method. Absolute depth- and background-corrected %DMSA were determined 24 h following the injection of 185 MBq per 1.73 m2 freshly prepared 99Tcm-DMSA. All patients had EDTA clearance 20 ml.min-1 (mean +/- S.D. = 30.9 +/- 13.8 ml.min-1), whereas 37 patients (group B: 22 women and 15 men, mean age 62.0 years, range 19-77 years) had EDTA clearance DMSA for the patients as a whole and for group A (r = 0.87, P = 0.73; r = 0.79, P = 0.0001 respectively). The regression equation suggests that %DMSA is not a marker of early renal dysfunction. In group B, the r-value (r = 0.48, P = 0.004) suggests that %DMSA is reliable as a marker of severe renal dysfunction to the extent that it provides rough information. In conclusion, %DMSA may not be used as a marker of early renal impairment. Additionally, in patients with severely reduced kidney function (EDTA clearance < 20 ml.min-1), it only provides a rough estimate.

  9. Evaluation of renal graft haemodynamia by 51Cr-EDTA and o-[131I]iodohippurate: its use in the early diagnosis of glomerular hyperfiltration.

    Science.gov (United States)

    Estorch, M; Tembl, A; Antonijoan, R; Hernandez, A; Mari, C; Flotats, A; Camacho, V; Sola, R; Barbanoj, M; Carrio, I

    2003-06-01

    Chronic rejection is the most important cause of renal graft dysfunction. Non-immunological mechanisms have been suggested as a probable origin of chronic graft rejection, provoking a decrease in renal mass function, followed by glomerular hyperfiltration in the remnant nephrons, which could cause progressive glomerulosclerosis and functional loss. Early, or preclinical, identification of patients with glomerular hyperfiltration, defined as an increase in glomerular filtration fraction (GFF) and in glomerular capillary pressure (GCP), could prolong graft life. The objective of this study was to evaluate, non-invasively, stable renal graft haemodynamia and early glomerular hyperfiltration. We studied 116 renal transplant patients with stable renal function and five healthy living kidney donors with normal renal function. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were determined using 51Cr-EDTA and o-[131I]iodohippurate, respectively. GFF was obtained from the relation between GFR and ERPF, and GCP from a mathematical model (Hall-Gomez' formula). A simultaneous analysis of renal function was performed. In transplant patients, the GFR and ERPF were significantly lower than in healthy, living, kidney donors (PGFF was not significantly different. Twelve patients (10.3%) had criteria of glomerular hyperfiltration. In patients without criteria of glomerular hyperfiltration, plasma level and clearance of creatinine were 128+/-33 micromol.l-1 and 56+/-15 ml.min-1, respectively; and in those patients with glomerular hyperfiltration criteria were 108+/-18 micromol.l-1 (P=NS) and 83+/-24 ml.min-1 (P=0.002) respectively. It is concluded that determinations of GFR, ERPF, GFF and GCP allow non-invasive evaluation of renal graft haemodynamia and can be useful in the early detection of glomerular hyperfiltration.

  10. Cadmium telluride detectors in the external measurement of glomerular filtration rate using 99mTc-DTPA(Sn): Comparison with /sup 51/Cr-EDTA and 99mTc-DTPA(Sn) plasma sample methods

    Energy Technology Data Exchange (ETDEWEB)

    Owen, J.E.; Walker, R.G.; D' Apice, A.J.F.; Willems, D.; Guignard, P.A.

    1982-01-01

    GFR was determined in 16 patients using an external detector to monitor disappearance of a single injected dose of 99mTc-DTPA (Sn) simultaneously with determinations of GFR using plasma sample methods for 99mTc-DTPA (Sn) and /sup 51/Cr-EDTA. Values of GFR were correlated closely between the external determinations of GFR and the plasma sample methods for /sup 51/Cr-EDTA and 99mTc-DTPA (Sn) with correlation coefficients of 0.97 and 0.99, respectively. Although the external detector method is apparently accurate, its advantages are as yet insufficient to warrant its adoption as the method of choice for determination of GFR.

  11. 188Re标记叶酸偶联白蛋白纳米微球对SKOV3人卵巢癌生长抑制作用研究*%The Inhibitory Effects of 188Re-Labeled Folate Coupling with Magnetic Albumin Nanoparticles on SKOV3 Ovarian Cancer in Vivo

    Institute of Scientific and Technical Information of China (English)

    唐秋莎; 陈道桢; 臧嘉; 郭彩琴

    2013-01-01

    Objective To investigate the effects of isotope labeled folate targeting albumin nanoparticles (188Re-fo-late-CDDP/HAS MNP) on human SKOV3 ovarian cancer cells in vivo. Methods The human SKOV3 ovarian cancer model was established in mice. Sixty-four tumor-bearing mice were randomly divided into eight groups:(A) negative control group, (B) chemotherapy group, (C) radiotherapy alone group, (D) hyperthermia alone group, (E) chemotherapy combined with radio-therapy group, (F) chemotherapy combined with hyperthermia therapy group, (G) radiotherapy combined with hyperthermia therapy group and (H) hyperthermia, chemotherapy and radiotherapy combined treatment group. After treatment, the cell pro-liferation and tumor growth were observed. The inhibitory rate of tumor mass was measured. The histopathological changes of tumor were observed in all groups. Results The quality of tumor was significantly lower in treatment groups than that of control group (P<0.05). There was the lowest quality of tumor in hyperthermia, chemotherapy and radiotherapy combined treatment group than that of other treatment groups (P<0.05). Conclusion The combination of magnetic induction hyper-thermia, chemotherapy, targeted radionuclide of radiation exposure can effectively inhibit the growth of ovarian cancer, which has the potential application for ovarian cancer treatment.%目的观察核素标记叶酸靶向白蛋白纳米微球(188Re-folate-CDDP/HAS MNP)对SKOV3人卵巢癌细胞生长作用的影响。方法建立人卵巢癌细胞SKOV3裸鼠模型,并将64只荷瘤鼠随机分成8组,每组8只,分别为(A)阴性对照组;(B)采用CDDP方案化疗的单纯化疗组;(C)核素靶向内照射的单纯放疗组;(D)磁感应热疗的单纯热疗组;(E)化疗联合放疗组;(F)化疗联合热疗治疗组;(G)放疗联合热疗治疗组;(H)热疗、化疗、放疗联合治疗组。各组经治疗后,观察肿瘤生长增殖情况,计算肿瘤质量抑

  12. Reassessment of a classical single injection 51Cr-EDTA clearance method for determination of renal function in children and adults. Part I: Analytically correct relationship between total and one-pool clearance

    DEFF Research Database (Denmark)

    Jødal, Lars; Brøchner-Mortensen, Jens

    2009-01-01

    and adults. Material and methods. Cl was determined in 149 subjects (M/F/children: 71/46/32) from a complete plasma concentration curve followed for 4-5 h after injection of 51Cr-EDTA (range of clearance: 8-183 mL/min/1.73 m²). Plasma volume, PV and the "missing" area under the plasma fraction curve......Background. Total plasma clearance of 51Cr-EDTA, Cl, is widely used as a measure of GFR. Commonly, only the final part of the plasma concentration curve is measured, and a one-pool clearance (slope-intercept clearance), Cl1, is computed. Empirically determined second-order polynomials......, a (minutes), not used for determination of Cl1, were measured. Results. The true relationship between Cl and Cl1 is given by Cl = Cl1/(1+f·Cl1), where f = a/PV. For men, women and children alike, the equation f = 0.0032·BSA-1.3 was applicable (BSA = body surface area in m²). Estimation errors on clearance...

  13. Preparation, Radiolabelling and Biodistribution Study of ~(177)Lu-DTPA-G3

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    Polyamidoamine (PAMAM) dendrimers are new artificial macromolecules with tree-like structure and have characteristics of greater water-solubility, bioavailability and compatibility. It can be carried by the drug molecules. PAMAM have been

  14. Preparation and 177Lu Labeling of p-SCN-Bn-DOTA-h-R3

    Institute of Scientific and Technical Information of China (English)

    DENG; Xin-rong; FAN; Cai-yun; LUO; Zhi-fu

    2013-01-01

    The humanized monoclonal antibodies(mAbs)h-R3 has been used as a targeting biomolecule better than other anti-EGFR(epidermal growth factor receptor)for the delivery of radionuclide onto tumor cells in radio immunotherapy(RIT).Several bifunctional chelating agents(BCAs)could be used as a bridge coupling h-R3 and radiometals.In this study,h-R3 was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,

  15. Production of {sup 177}Lu, a potential radionuclide for diagnostic and therapeutic applications

    Energy Technology Data Exchange (ETDEWEB)

    Khandaker, Mayeen Uddin; Kassim, Hasan Abu [Department of Physics, University of Malaya, 50603 Kuala Lumpur (Malaysia); Haba, Hiromitsu [Nishina Center for Accelerator-Based Science, RIKEN, Wako, Saitama 351-0198 (Japan)

    2015-04-24

    {sup 177g}Lu (T{sub 1/2}=6.647d; E{sub β{sup −max}}=498.3KeV, I{sub β{sup −total}}=100%; E{sub γ} = 112.9498 keV, I{sub γ} = 6.17%; E{sub γ} = 208.3662 keV, I {sub γ} = 10.36%) is widely used in many clinical procedures due to its excellent decay characteristics. Production cross-sections of the {sup nat}Yb(d,x){sup 177g}Lu reactions have been measured from a 24-MeV deuteron energy down to the threshold by using a stacked-foil activation technique combined with high resolution γ-ray spectrometry. An overall good agreement is found with some of the earlier measurements, whereas a partial agreement is obtained with the theoretical data extracted from the TENDL-2013 library. Physical thick target yield for the {sup 177g}Lu radionuclide was deduced using the measured cross-sections. The deduced yield curves indicate that a low energy (<11 MeV) cyclotron and a highly enriched {sup 176}Yb target could be used to obtain {sup 177g}Lu with negligible impurity from {sup 177m}Lu.

  16. Exaggerated natriuretic response to isotonic volume expansion in hypertensive renal transplant recipients: evaluation of proximal and distal tubular reabsorption by simultaneous determination of renal plasma clearance of lithium and 51Cr-EDTA.

    Science.gov (United States)

    Nielsen, A H; Knudsen, F; Danielsen, H; Pedersen, E B; Fjeldborg, P; Madsen, M; Brøchner-Mortensen, J; Kornerup, H J

    1987-02-01

    In fourteen hypertensive and fourteen normotensive renal transplant recipients, and in a group of thirteen healthy controls, changes in natriuresis, glomerular filtration rate (GFR), and tubular reabsorption of sodium were determined in relation to intravenous infusion of 2 mmol isotonic sodium chloride per kg body weight. An exaggerated natriuresis was demonstrated in the hypertensive renal transplant recipients. This new finding indicates that the augmented natriuresis following plasma volume expansion, which is a characteristic finding in subjects with arterial hypertension, is not mediated by the renal nerves. Investigation of the tubular reabsorption rates of sodium by simultaneous determination of the renal clearance of 51Cr-EDTA and lithium showed that in the hypertensives the changes in tubular handling of sodium were different from those registered in the normotensive subjects. The increased sodium excretion in the hypertensive renal transplant recipients was caused by an increased output of sodium from the proximal tubules which was not fully compensated for by an increased distal reabsorption. Whether this increased delivery of sodium to the distal segments was caused by changes in GFR or in the proximal tubular reabsorption of sodium could not be clarified in the present study and warrants further investigations.

  17. Favourable outcomes of {sup 177}Lu-octreotate peptide receptor chemoradionuclide therapy in patients with FDG-avid neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kashyap, Raghava [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Hofman, Michael S.; Kong, Grace; Akhurst, Timothy; Eu, Peter [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Peter MacCallum Cancer Centre, Neuroendocrine Tumour Service, Melbourne (Australia); Michael, Michael [University of Medicine, Department of Medicine, Melbourne (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia); Zannino, Diana [Peter MacCallum Cancer Centre, Biostatistics and Clinical Trials, Melbourne (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Center, Centre for Cancer Imaging, Melbourne (Australia); Peter MacCallum Cancer Centre, Neuroendocrine Tumour Service, Melbourne (Australia); University of Melbourne, The Sir Peter MacCallum Department of Oncology, Melbourne (Australia)

    2014-09-11

    Increased glycolytic activity on FDG PET/CT defines a subgroup of patients with metastatic gastroenteropancreatic neuroendocrine tumour (NET) with a poor prognosis. A limited range of systemic treatment options exist for more aggressive NET. The role of peptide receptor chemoradionuclide therapy (PRCRT) in such patients is, however, unclear. This retrospective study assessed the outcomes of patients with FDG-avid NET treated with PRCRT. Clinical, biochemical and imaging response was assessed after completion of induction treatment of PRCRT with 5-fluorouracil in 52 patients selected for treatment on the basis of somatostatin-receptor imaging without spatially discordant FDG-avid disease. Of the cohort, 67 % had received prior chemotherapy. Overall survival (OS) and progression-free survival (PFS) were also analysed. PRCRT was well tolerated with negligible grade 3/4 toxicities. After a median follow-up period of 36 months, the median OS was not achieved with a median PFS of 48 months. At 3 months after completion of PRCRT 2 % of patients showed a complete anatomical response, 28 % a partial response, 68 % stable disease, and only 2 % progression. On FDG PET/CT, 27 % achieved a complete metabolic response during the follow-up period. A biochemical response (>25 % fall in chromogranin-A levels) was seen in 45 %. PRCRT is an effective treatment in patients with FDG-avid NET, even in patients who have failed conventional therapies. Given apparently higher response rates than with alternative therapeutic options and low toxicity, further research is needed to establish whether PRCRT should be used as a first-line treatment modality in this patient population. (orig.)

  18. 188Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside

    Science.gov (United States)

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (Eβmax = 2.1 MeV) for the treatment of HCC. The major “milestones” of this development, from the first syntheses to the recent first injection in man, are described. PMID:22518301

  19. (188)Re-SSS/Lipiodol: Development of a Potential Treatment for HCC from Bench to Bedside.

    Science.gov (United States)

    Lepareur, Nicolas; Ardisson, Valérie; Noiret, Nicolas; Garin, Etienne

    2012-01-01

    Hepatocellular carcinoma (HCC) is the 5th most common tumour worldwide and has a dark prognosis. For nonoperable cases, metabolic radiotherapy with Lipiodol labelled with β-emitters is a promising therapeutic option. The Comprehensive Cancer Centre Eugène Marquis and the National Graduate School of Chemistry of Rennes (ENSCR) have jointly developed a stable and efficient labelling of Lipiodol with rhenium-188 (E(βmax) = 2.1 MeV) for the treatment of HCC. The major "milestones" of this development, from the first syntheses to the recent first injection in man, are described.

  20. Dosimetric studies of anti-CD20 labeled with therapeutic radionuclides at IPEN/CNEN-SP

    Energy Technology Data Exchange (ETDEWEB)

    Barrio, G.; Dias, C.R.B.R.; Osso Junior, J.A., E-mail: gracielabarrio@gmail.com [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2012-07-01

    Radioimmunotherapy (RIT) makes use of monoclonal antibodies (MAb) labeled with alpha/beta radionuclides for therapeutical purposes, leading to tumor irradiation and destruction, preserving the normal organs on the radiation excess. The therapeutic activity to be injected in a specific patient is based on information obtained in dosimetric studies. Beta emitting radionuclides such as {sup 131}I, {sup 188}Re, {sup 90}Y, {sup 177}Lu and {sup 166}Ho are useful for the development of therapeutic radiopharmaceuticals. Anti-CD20 (Rituximab) is a chimeric MAb directed against antigen surface CD20 on B-lymphocytes, used in non-Hodgkin lymphoma treatment (NHL). The association with beta radionuclides have shown greater therapeutic efficacy. Currently, two radiopharmaceuticals with Anti-CD20 for radioimmunotherapy have FDA approval for NHL treatment: {sup 131}I-AntiCD20 (Bexar) and {sup 90}Y-AntiCD20 (Zevalin). Techniques for the radiolabeling of {sup 188}Re-antiCD20 have been recently developed by IPEN-CNEN/SP in order to evaluate the clinical use of this radionuclide in particular. The use of {sup 188}Re (T{sub 1/2} 17h) produced by the decay of {sup 188}W (T{sub 1/2} 69d), from an {sup 188}W/{sup 188}Re generator system, has represented an alternative to RIT. Beyond high energy beta emission for therapy, {sup 188}Re also emits gamma rays (155keV) suitable for image. The aim of this new project is to compare the labeling of anti-CD20 with {sup 188}Re with the same MAb labeled with {sup 131}I, {sup 177}Lu, {sup 90}Y and even {sup 99m}Tc. The first step in this project is the review of the published data available concerning the labeling of this MAb with different radionuclides, along with data obtained at IPEN, taking into account labeling procedures, labeling yields, reaction time, level and kind of impurities and biodistribution studies. The pharmacokinetic code will be developed in Visual Studio.NET platform through VB.NET and C{sup ++} for biodistribution and dosimetric

  1. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2014-09-01

    Christos, Marina Mikhail, John Chapin, David M. Nanus, Scott T. Tagawa Division of Hematology & Medical Oncology Weill Cornell Medical College Disclosures...Genetics, $26,196,300 Therapy and Mechanisms of Resistance, $87,912,713 Tumor Biology and Immunology, $51,016,047 In This Issue page 1

  2. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Biochemically Monoclonal Antibody J591 in Patients with High-Risk Castrate, Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2010-09-01

    review on hold pending additional funding - University of Medicine and Dentistry , New Jersey – scientific review - Nevada Cancer Institute – scientific...BIOCHEMICALLY RELAPSED PROSTATE CANCER AFTER LOCAL THERAPY Scott T. Tagawa, Joseph Osborne, Paul J. Christos, Shankar Vallabhajosula, Kristen Petrillo

  3. (99m)Tc HYNIC-TOC imaging and 177Lu DOTA-octreotate treatment in non-iodine-concentrating dedifferentiated thyroid carcinoma metastases: an unusual alternative diagnosis.

    Science.gov (United States)

    Basu, Sandip; Joshi, Amit

    2014-07-01

    The value of Tc HYNIC-TOC scintigraphy clarifying skeletal and hepatic-predominant metastatic disease in a 55-year-old woman (diagnosed earlier to have papillary carcinoma thyroid and had undergone total thyroidectomy and radioiodine ablation) is illustrated. The whole-body radioiodine scan and battery of serum tumor markers were normal. Multiple metastatic foci in the liver and skeleton were Tc HYNIC-TOC avid. Serum chromogranin A level was substantially elevated (1771.60 ng/mL). This represents an unusual alternative diagnosis signified by a highly positive scan in the setting of apparent non-iodine-concentrating metastatic disease in a patient of differentiated thyroid carcinoma.

  4. A Randomized Phase 2 Trial of 177Lu Radiolabeled Anti-PSMA Monoclonal Antibody J591 in Patients With High-Risk Castrate Biochemically Relapsed Prostate Cancer

    Science.gov (United States)

    2015-09-01

    Sincerely , Rosemary Kraemer, Ph.D. Director, Human Research Protections Program Please note the following important information about this approval...sciences journal literature , and be made publicly available within twelve months of publication. The Library and RASP have prepared general information

  5. Dynamic and static small-animal SPECT in rats for monitoring renal function after 177Lu-labeled Tyr3-octreotate radionuclide therapy.

    NARCIS (Netherlands)

    Melis, M.; Swart, J.; Visser, M. de; Berndsen, S.C.; Koelewijn, S.; Valkema, R.; Boerman, O.C.; Krenning, E.P.; Jong, M. de

    2010-01-01

    High kidney radiation doses during clinical peptide receptor radionuclide therapy (PRRT) with beta-particle-emitting radiolabeled somatostatin analogs will lead to renal failure several months after treatment, urging the coinfusion of the cationic amino acids lysine and arginine to reduce the renal

  6. Peptide receptor radionuclide therapy with Y-DOTATOC and (177)Lu-DOTATOC in advanced neuroendocrine tumors: results from a Danish cohort treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  7. Peptide Receptor Radionuclide Therapy with (90)Y-DOTATOC and (177)Lu-DOTATOC in Advanced Neuroendocrine Tumors: Results from a Danish Cohort Treated in Switzerland

    DEFF Research Database (Denmark)

    Pfeifer, Andreas Klaus; Gregersen, Tine; Grønbæk, Henning

    2011-01-01

    Limited therapeutic options have highlighted the demand for new treatment modalities for patients with advanced neuroendocrine tumors (NET). Promising results of initial studies have warranted the implementation of peptide receptor radionuclide therapy (PRRT) in clinical practice. However, this t...

  8. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma.

    Directory of Open Access Journals (Sweden)

    Ada H V Repetto-Llamazares

    Full Text Available 177Lu-DOTA-HH1 (177Lu-HH1 is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1 and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1.

  9. Targeted Cancer Therapy with a Novel Anti-CD37 Beta-Particle Emitting Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

    Science.gov (United States)

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Patzke, Sebastian; Fleten, Karianne G.; Didierlaurent, David; Pichard, Alexandre; Pouget, Jean Pierre; Dahle, Jostein

    2015-01-01

    177Lu-DOTA-HH1 (177Lu-HH1) is a novel anti-CD37 radioimmunoconjugate developed to treat non-Hodgkin lymphoma. Mice with subcutaneous Ramos xenografts were treated with different activities of 177Lu-HH1, 177Lu-DOTA-rituximab (177Lu-rituximab) and non-specific 177Lu-DOTA-IgG1 (177Lu-IgG1) and therapeutic effect and toxicity of the treatment were monitored. Significant tumor growth delay and increased survival of mice were observed in mice treated with 530 MBq/kg 177Lu-HH1 as compared with mice treated with similar activities of 177Lu-rituximab or non-specific 177Lu-IgG1, 0.9% NaCl or unlabeled HH1. All mice injected with 530 MBq/kg of 177Lu-HH1 tolerated the treatment well. In contrast, 6 out of 10 mice treated with 530 MBq/kg 177Lu-rituximab experienced severe radiation toxicity. The retention of 177Lu-rituximab in organs of the mononuclear phagocyte system was longer than for 177Lu-HH1, which explains the higher toxicity observed in mice treated with 177Lu-rituximab. In vitro internalization studies showed that 177Lu-HH1 internalizes faster and to a higher extent than 177Lu-rituximab which might be the reason for the better therapeutic effect of 177Lu-HH1. PMID:26066655

  10. Decline in 51Cr-labelled EDTA measured glomerular filtration rate following lung transplantation

    DEFF Research Database (Denmark)

    Hornum, Mads; Burton, Christopher M; Iversen, Martin;

    2007-01-01

    -labelled EDTA clearance (mGFR) and the Cockcroft-Gault calculated clearance (cGFR). Trough cyclosporine levels (C0) and demographic and transplant information were also included in the analysis. RESULTS: A total of 66959 C0 and serum creatinine and 1945 mGFR measurements pertaining to 383 patients were included...

  11. Radioisotopes production for applications on the health; Produccion de radioisotopos para aplicaciones en la salud

    Energy Technology Data Exchange (ETDEWEB)

    Monroy G, F.; Alanis M, J., E-mail: fabiola.monroy@inin.gob.m [ININ, Departamento de Materiales Radiactivos, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2010-07-01

    In the Radioactive Materials Department of the Instituto Nacional de Investigaciones Nucleares (ININ) processes have been studied and developed for the radioisotopes production of interest in the medicine, research, industry and agriculture. In particular five new processes have been developed in the last 10 years by the group of the Radioactive Materials Research Laboratory to produce: {sup 99}Mo/{sup 99m}Tc and {sup 188}W/{sup 188}Re generators, the radio lanthanides: {sup 151}Pm, {sup 147}Pm, {sup 161}Tb, {sup 166}Ho, {sup 177}Lu, {sup 131}I and the {sup 32}P. All these radioisotopes are artificial and they can be produced in nuclear reactors and some of them in particle accelerators. The radioisotope generators are of particular interest, as those of {sup 99}Mo/{sup 99m}Tc and {sup 188}W/{sup 188}Re presented in this work, because they are systems that allow to produce an artificial radioisotope of interest continually, in these cases the {sup 99m}Tc and the {sup 188}Re, without the necessity of having a nuclear reactor or an particle accelerator. They are compact systems armored and sure perfectly of manipulating that, once the radioactive material has decayed, they do not present radiological risk some for the environment and the population. These systems are therefore of supreme utility in places where it is not had nuclear reactors or with a continuous radioisotope supply, due to their time of decaying, for its cost or for logistical problems in their supply, like it is the case of many hospital centers, of research or industries in our country. (Author)

  12. 'Reverse discordance' between 68Ga-DOTA-NOC PET/CT and 177Lu-DOTA-TATE posttherapy scan: the plausible explanations and its implications for high-dose therapy with radiolabeled somatostatin receptor analogs.

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit; Kand, Purushottam; Kumar, Rakesh; Asopa, Ramesh; Rajan, Mysore Govinda Ramakrishna; Nayak, Uday; Shimpi, Hemant; Das, Tapas; Venkatesh, Meera; Chakrabarty, Sudipta; Banerjee, Sharmila

    2011-07-01

    In this technical note, an unusual discordance between diagnostic and posttherapeutic scan resulting from the use of different somatostatin receptor ligands in two settings is described. Such observation, we believe, is multifactorial, but most importantly arises due to different receptor affinity profile of the ligands and different somatostatin receptor subtype expression in different tumors. It is important for the treating physician to be aware of this phenomenon that would aid in improving our understanding of complex ligand-receptor interactions in various somatostatin receptor-positive tumors with its possible implications for therapeutic decision making with radiolabeled somatostatin receptor analogues.

  13. Obtaining of the cellular S values by means of Monte Carlo simulation with Penelope and MCNPX; Obtencion de los valores S celulares mediante simulacion Monte Carlo con PENELOPE y MCNPX

    Energy Technology Data Exchange (ETDEWEB)

    Rojas C, E. L.; Avila, O., E-mail: leticia.rojas@inin.gob.mx [ININ, Carretera Mexico-Toluca s/n, 52750 Ocoyoacac, Estado de Mexico (Mexico)

    2012-10-15

    In this work the simulation codes Monte Carlo, Penelope and MCNPX were used to calculate the doses by unit of accumulated activity S(N-N) in water spherical cells models of different radius exposed to mono-energetics electrons coming from punctual sources located in the center of the cellular nucleus. The studied cellular radii were: r{sub n}1=3 r{sub c}1=6; r{sub n}2=5 and r{sub c}2=10; r{sub n}3=9 and r{sub c}3=10 {mu}m; being r{sub n} and r{sub c} the nuclear and cellular radius, respectively. The following initial energies of the electrons were considered: 1, 5, 10, 50, 100, 500, 700 and 1000 keV. Additionally values S(N-N) were calculated for spherical cells of r= 3 {mu}m r{sub c}= 6 {mu}m due to the electrons coming from sources of {sup 111}In, {sup 177}Lu, {sup 99m}Tc, {sup 188}Re and {sup 186}Re. The obtained values are compared with those calculated by the MIRD Committee internationally accepted. The percentage differences between the values reported by this Committee and those calculated by Monte Carlo simulation are inside the interval that is considered valid for this dosimetry type. A major concordance was found among the values calculated by Monte Carlo simulation that among those calculated by MIRD and those obtained by simulation. Considering validated the use of both codes for similar applications, the values S(N-N) and S(N-C y) were obtained of prostate cancer real cells models of the PC3 line. The results were compared among them. The values of S(N-N) obtained with Penelope for the PC3 cells for the electron emissions of {sup 111}In, {sup 177}Lu, {sup 99m}Tc, {sup 188}Re and {sup 186}Re are: 3.19e{sup {sub {sup 4}}}, 3.24e{sup -4}, 1.37e{sup -4}, 1.11e{sup -4} and 1.91e{sup -4} Gy/Bq-s, respectively. Also the obtained results for S(N-C y) are: 2.95e{sup -6}, 3.17e{sup -5}, 2.09e{sup -6}, 1.41e{sup -5}, 1.86e{sup -5} Gy/Bq-s. (Author)

  14. Contribution to the study of the biological properties of compounds labeled with radio-chromium {sup 51}Cr; Contribution a l'etude des proprietes biologiques des composes marques au radiochrome {sup 51}Cr

    Energy Technology Data Exchange (ETDEWEB)

    Ingrand, J. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1964-07-15

    Among the radioisotopes commonly used in biology and medicine which are controlled Individually in the Radioelement Departement of the Saclay Nuclear Research Centre before being sent to the users, the author has chosen chromium 51 incorporated in inorganic salts or in organic substrates for a study of the biological properties of the compounds. In the first part, he has compared the pathways followed by the radioactive sodium chromate and chromic chloride mixed with blood or given to the whole animal, the object being to determine whether a reduction of hexavalent chromium occurs, both in vitro and in vivo. In the second part, the author has tried to show the validity of using, various substrates labeled with chromium 51, red cells, haemoglobin, plasma proteins and cytochrome c. The results obtained have contributed to underline the interest of using such compounds for biological applications. (author) [French] Parmi les radioisotopes d'utilisation courants en biologie et en medecine qui sont l'objet d'un controle particulier dans le Departement des Radioelements du Centre d'Etudes Nucleaires de Saclay avant leur diffusion aux utilisateurs, l'auteur a choisi le chrome 51 incorpore a des sels mineraux ou a des substrats organiques, afin d'en etudier les proprietes biologiques. Dans la premiere partie, il a compare le sort du chromate de sodium et du chlorure chromique radioactifs melanges a du sang ou administres a l'animal entier en s'efforcant de mettre en evidence une reduction du chrome hexavalent aussi bien in vitro qu'in vivo. Dans la deuxieme partie, il a cherche a etablir la validite de l'emploi de differents substrats marques au chrome 51, l'hematie, l'hemoglobine, les proteines plasmatiques et le cytochrome c. Les resultats obtenus ont permis de souligner le reel interet des applications biologiques des composes marques par le radioisotope. (auteur)

  15. Calculation of electron and isotopes dose point kernels with FLUKA Monte Carlo code for dosimetry in nuclear medicine therapy

    CERN Document Server

    Mairani, A; Valente, M; Battistoni, G; Botta, F; Pedroli, G; Ferrari, A; Cremonesi, M; Di Dia, A; Ferrari, M; Fasso, A

    2011-01-01

    Purpose: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, FLUKA Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, FLUKA has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one. Methods: FLUKA DPKS have been calculated in both water and compact bone for monoenergetic electrons (10-3 MeV) and for beta emitting isotopes commonly used for therapy ((89)Sr, (90)Y, (131)I, (153)Sm, (177)Lu, (186)Re, and (188)Re). Point isotropic...

  16. Rapid decline in 51Cr-EDTA measured renal function during the first weeks following lung transplantation

    DEFF Research Database (Denmark)

    Hornum, M.; Iversen, M.; Steffensen, I.;

    2009-01-01

    We previously described a 54% decline in renal function at 6 months after lung transplantation (LTx). We hypothesized that this decline is a very early event following LTx. Thirty-one consecutive patients (16 females/15 males), mean age 49 (+/-13) years, with emphysema, cystic fibrosis/bronchiect...

  17. Melanoma Therapy with Rhenium-Cyclized Alpha Melanocyte Stimulating Hormone Peptide Analogs

    Energy Technology Data Exchange (ETDEWEB)

    Thomas P Quinn

    2005-11-22

    Malignant melanoma is the 6th most commonly diagnosed cancer with increasing incidence in the United States. It is estimated that 54,200 cases of malignant melanoma will be newly diagnosed and 7,600 cases of death will occur in the United States in the year 2003 (1). At the present time, more than 1.3% of Americans will develop malignant melanoma during their lifetime (2). The average survival for patients with metastatic melanoma is about 6-9 months (3). Moreover, metastatic melanoma deposits are resistant to conventional chemotherapy and external beam radiation therapy (3). Systematic chemotherapy is the primary therapeutic approach to treat patients with metastatic melanoma. Dacarbazine is the only single chemotherapy agent approved by FDA for metastatic melanoma treatment (5). However, the response rate to Dacarbazine is only approximately 20% (6). Therefore, there is a great need to develop novel treatment approaches for metastatic melanoma. The global goal of this research program is the rational design, characterization and validation of melanoma imaging and therapeutic radiopharmaceuticals. Significant progress has been made in the design and characterization of metal-cyclized radiolabeled alpha-melanocyte stimulating hormone peptides. Therapy studies with {sup 188}Re-CCMSH demonstrated the therapeutic efficacy of the receptor-targeted treatment in murine and human melanoma bearing mice (previous progress report). Dosimetry calculations, based on biodistribution data, indicated that a significant dose was delivered to the tumor. However, {sup 188}Re is a very energetic beta-particle emitter. The longer-range beta-particles theoretically would be better for larger tumors. In the treatment of melanoma, the larger primary tumor is usually surgically removed leaving metastatic disease as the focus of targeted radiotherapy. Isotopes with lower beta-energies and/or shorter particle lengths should be better suited for targeting metastases. The {sup 177}Lu

  18. Development of new techniques for using an atomic reactor in the study of agricultural environment and expansion of its utilization

    Energy Technology Data Exchange (ETDEWEB)

    Yuita, Koichi; Yamazaki, Shinichi; Akiyama, Tsuyoshi; Ota, Takeshi; Taniyama, Ichiro; Sakurai, Yasuhiro; Makino, Tomoyuki; Takahashi, Yoshiaki [National Inst. of Agro-Environmental Sciences, Tsukuba, Ibaraki (Japan)

    1997-02-01

    This study was made aiming to establish a method for simultaneous determinations of elements in soil. In the last year, the determination for elements having half lives of 2 weeks or less was performed and so, this study attempted to establish a determination method for 11 elements with longer half lives. When the determination by radiation analysis was carried out after cooling period of 1 week for {sup 76}As, {sup 122}Sb, {sup 131}Ba, {sup 140}La, {sup 147}Nd, {sup 153}Sm and {sup 175}Yb, and of 2 weeks for {sup 46}Sc, {sup 51}Cr, {sup 60}Co, {sup 86}Rb, {sup 141}Ce, {sup 152}Eu, {sup 177}Lu, {sup 181}Hf and {sup 182}Ta, quantification of these rare elements were able with a good accuracy and in a relatively short time by using the correction with titanium as the internal standard element. Then, to elucidate the relationship between the elution profiles of heavy metals in soil and the characteristics of organic compounds in soil, the conditions for neutron irradiation for direct labelling of heavy metals and those for water elution of those metals were investigated. The present results indicate that the profile of water elution might be influenced by the characteristics of organic compounds in soil. (M.N.)

  19. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions

    Science.gov (United States)

    Lanconelli, N.; Pacilio, M.; Lo Meo, S.; Botta, F.; Di Dia, A.; Torres Aroche, L. A.; Coca Pérez, M. A.; Cremonesi, M.

    2012-01-01

    The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

  20. Pharmaceutical and clinical development of phosphonate-based radiopharmaceuticals for the targeted treatment of bone metastases.

    Science.gov (United States)

    Lange, Rogier; Ter Heine, Rob; Knapp, Russ Ff; de Klerk, John M H; Bloemendal, Haiko J; Hendrikse, N Harry

    2016-10-01

    Therapeutic phosphonate-based radiopharmaceuticals radiolabeled with beta, alpha and conversion electron emitting radioisotopes have been investigated for the targeted treatment of painful bone metastases for >35years. We performed a systematic literature search and focused on the pharmaceutical development, preclinical research and early human studies of these radiopharmaceuticals. The characteristics of an ideal bone-targeting therapeutic radiopharmaceutical are presented and compliance with these criteria by the compounds discussed is verified. The importance of both composition and preparation conditions for the stability and biodistribution of several agents is discussed. Very few studies have described the characterization of these products, although knowledge on the molecular structure is important with respect to in vivo behavior. This review discusses a total of 91 phosphonate-based therapeutic radiopharmaceuticals, of which only six agents have progressed to clinical use. Extensive clinical studies have only been described for (186)Re-HEDP, (188)Re-HEDP and (153)Sm-EDTMP. Of these, (153)Sm-EDTMP represents the only compound with worldwide marketing authorization. (177)Lu-EDTMP has recently received approval for clinical use in India. This review illustrates that a thorough understanding of the radiochemistry of these agents is required to design simple and robust preparation and quality control methods, which are needed to fully exploit the potential benefits of these theranostic radiopharmaceuticals. Extensive biodistribution and dosimetry studies are indispensable to provide the portfolios that are required for assessment before human administration is possible. Use of the existing knowledge collected in this review should guide future research efforts and may lead to the approval of new promising agents.

  1. A free database of radionuclide voxel S values for the dosimetry of nonuniform activity distributions.

    Science.gov (United States)

    Lanconelli, N; Pacilio, M; Lo Meo, S; Botta, F; Di Dia, A; Aroche, A Torres; Pérez, M A Coca; Cremonesi, M

    2012-01-21

    The increasing availability of SPECT/CT devices with advanced technology offers the opportunity for the accurate assessment of the radiation dose to the biological target volume during radionuclide therapy. Voxel dosimetry can be performed employing direct Monte Carlo radiation transport simulations, based on both morphological and functional images of the patient. On the other hand, for voxel dosimetry calculations the voxel S value method can be considered an easier approach than patient-specific Monte Carlo simulations, ensuring a good dosimetric accuracy at least for anatomic regions which are characterized by uniform density tissue. However, this approach has been limited because of the lack of tabulated S values for different voxel dimensions and radionuclides. The aim of this work is to provide a free dataset of values which can be used for voxel dosimetry in targeted radionuclide studies. Seven different radionuclides (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, 188Re), and 13 different voxel sizes (2.21, 2.33, 2.4, 3, 3.59, 3.9, 4, 4.42, 4.8, 5, 6, 6.8 and 9.28 mm) are considered. Voxel S values are calculated performing simulations of monochromatic photon and electron sources in two different homogeneous tissues (soft tissue and bone) with DOSXYZnrc code, and weighting the contributions on the basis of the radionuclide emission spectra. The outcomes are validated by comparison with Monte Carlo simulations obtained with other codes (PENELOPE and MCNP4c) performing direct simulation of the radionuclide emission spectra. The differences among the different Monte Carlo codes are of the order of a few per cent when considering the source voxel and the bremsstrahlung tail, whereas the highest differences are observed at a distance close to the maximum continuous slowing down approximation range of electrons. These discrepancies would negligibly affect dosimetric assessments. The dataset of voxel S values can be freely downloaded from the website www.medphys.it.

  2. Individual monitoring of internal exposure for nuclear medicine workers in Switzerland.

    Science.gov (United States)

    Baechler, S; Stritt, N; Bochud, F O

    2011-03-01

    Monitoring of internal exposure for nuclear medicine workers requires frequent measurements due to the short physical half-lives of most radionuclides used in this field. The aim of this study was to develop screening measurements performed at the workplace by local staff using standard laboratory instrumentation, to detect whether potential intake has occurred. Such measurements do not enable to determine the committed effective dose, but are adequate to verify that a given threshold is not exceeded. For radioiodine, i.e. (123)I, (124)I, (125)I and (131)I, a calibrated surface contamination monitor is placed in front of the thyroid to detect whether the activity threshold has been exceeded. For radionuclides with very short physical half-lives (≤ 6 h), such as (99m)Tc and those used in positron emission tomography imaging, i.e. (11)C, (15)O, (18)F and (68)Ga, screening procedures consist in performing daily measurements of the ambient dose rate in front of the abdomen. Other gamma emitters used for imaging, i.e. (67)Ga, (111)In and (201)Tl, are measured with a scintillation detector located in front of the thorax. For pure beta emitters, i.e. (90)Y and (169)Er, as well as beta emitters with low-intensity gamma rays, i.e. (153)Sm, (177)Lu, (186)Re and (188)Re, the procedure consists in measuring hand contamination immediately after use. In Switzerland, screening procedures have been adopted by most nuclear medicine services since such measurements enable an acceptable monitoring while taking into account practical and economic considerations.

  3. Direct contamination of barley with /sup 51/Cr, /sup 59/Fe, /sup 58/Co, /sup 65/Zn, /sup 203/Hg and /sup 210/Pb

    Energy Technology Data Exchange (ETDEWEB)

    Aarkrog, A.; Lippert, J.

    1971-01-01

    A study is reported of barley sprayed at six different stages of development with radionuclides of Cr, Fe, Co, Zn, Hg and Pb. The initial retention followed the equation: IR = 1-e/sub -0.31 g.cm-1/, where g is the dry weight of the herbage in a plot in grammes, and cm the height of the plants at spraying. The field loss depended on the growing rate and the development of the plants and thus varied throughout the growing period. The field loss coefficient ..gamma.. was 0.054 days/sup -1/ in the first part of the period and 0.017 days/sup -1/ in the second part. If the whole growing season is considered, the loss of activity in percent is about equal to the time in days from the spraying to harvest. Zn and Co showed the highest concentrations in the grain. The translocation of Cr, Pb and Hg within the plant was small. Fe was translocated to the grain as was Zn, but to a far less extent.

  4. ¹⁷⁷Lu-Labeled Agents for Neuroendocrine Tumor Therapy and Bone Pain Palliation in Uruguay.

    Science.gov (United States)

    Balter, Henia; Victoria, Trindade; Mariella, Terán; Javier, Gaudiano; Rodolfo, Ferrando; Andrea, Paolino; Graciela, Rodriguez; Juan, Hermida; Eugenia, De Marco; Patricia, Oliver

    2016-01-01

    Lutetium-177 is an emerging radionuclide due its convenient chemical and nuclear properties. In this paper we describe the development and evaluation in Uruguay of the targeted 177Lu labelled radiopharmaceuticals EDTMP (for bone pain palliation) and DOTA-TATE (neuroendocrine tumors). We optimized the preparation of these 177Lu radiopharmaceuticals including radiolabelling, quality control methods, in vitro and in vivo stability and their therapeutic application in patients. Radiation dosimetry aspects of 177Lu are also included. Nine male patients with prostate cancer and four female patients with breast carcinoma with multiple bone metastatic lesions were treated with 177Lu-EDTMP. Four patients with gastroentheropancreatic neuroendocrine tumors (GEP-NET) and one patient with bronchial NET were treated with 1- 3 cycles with a cumulative dose of 4.44-22.2 GBq of 177Lu-DOTA-TATE. Scintigraphic images of the patients treated with 177Lu-EDTMP evidenced high and rapid uptake in bone metastasis, remaining after 7 days post administration. Images allow skeletal visualization with high definition and demonstrate increased uptake in bone metastases. For 177Lu-DOTA-TATE, partial remissions were obtained in 4 patients and the remaining patient did not show significant progression 3 months after the second cycle. No serious adverse effects were registered, even in two patients with confirmed renal disease and high risk for renal disease Dosimetry assessments confirm the predictive value of the personalized therapy with radiolabelled peptides. We found it is possible to accumulate high therapeutic doses in tumours in sequential administrations of 177Lu-DOTA-TATE, increasing the probability of biological response without significant impairment of the renal function in patients with risk factors. These results demonstrate the attractive therapeutic properties of these two 177Lu labelled agents and the feasibility of this metabolic therapy in regions far away from 177Lu producing

  5. Radiopharmaceuticals for the therapy of metastatic bone pain

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Byeong Cheol [Kyungpook National University Medicine School, Daegu (Korea, Republic of)

    2006-04-15

    Bone metastasis is a common sequelae of solid malignant tumors such as prostate, breast, lung, and renal cancers, which can lead to various complications, including fractures, hypercalcemia, and bone pain, as well as reduced performance status and quality of life. It occurs as a result of a complex pathophysiologic process between host and tumor cells leading to cellular invasion, migration adhesion, and stimulation of osteoclastic and osteoblastic activity. Several sequelae occur as a result of osseous metastases and resulting bone pain can lead to significant debilitation. A multidisciplinary approach is usually required not only to address the etiology of the pain and is complicating factors but also to treat the patient appropriately. Pharmaceutical therapy of bone pain, includes non-steroidal analgesics, opiates, steroids, hormones, bisphosphonates, and chemotherapy. While external beam radiation therapy remains the mainstay of pain palliation of a solitary lesions, bone seeking radiopharmaceuticals have entered the therapeutic armamentarium for the treatment of multiple painful osseous lesion. {sup 32}P, {sup 89}SrCl, {sup 153}Sm-EDTMP, {sup 188}Re/{sup 186}Re-HEDP, and {sup 177}Lu-EDTMP can be used to treat painful osseous metastases. These various radiopharmaceuticals have shown good efficacy in relieving bone pain secondary to bone metastasis. This systemic from of metabolic radiotherapy is simple to administer and complements other treatment options. This has been associated with improved mobility in many patients, reduced dependence on narcotic and non-narcotic analgesics, improved performance status and quality of life, and in some studies, improved survival. All of these agents, although comprising different physical and chemical characteristics, offer certain advantages in that they are simple to administer, are well tolerated by the patient if used appropriately, and can be used alone or in combination with the other forms of treatment. This article

  6. Accounting for beta-particle energy loss to cortical bone via paired-image radiation transport (PIRT).

    Science.gov (United States)

    Shah, Amish P; Rajon, Didier A; Patton, Phillip W; Jokisch, Derek W; Bolch, Wesley E

    2005-05-01

    Current methods of skeletal dose assessment in both medical physics (radionuclide therapy) and health physics (dose reconstruction and risk assessment) rely heavily on a single set of bone and marrow cavity chord-length distributions in which particle energy deposition is tracked within an infinite extent of trabecular spongiosa, with no allowance for particle escape to cortical bone. In the present study, we introduce a paired-image radiation transport (PIRT) model which provides a more realistic three-dimensional (3D) geometry for particle transport in the skeletal site at both microscopic and macroscopic levels of its histology. Ex vivo CT scans were acquired of the pelvis, cranial cap, and individual ribs excised from a 66-year male cadaver (BMI of 22.7 kg m(-2)). For the three skeletal sites, regions of trabecular spongiosa and cortical bone were identified and segmented. Physical sections of interior spongiosa were taken and subjected to microCT imaging. Voxels within the resulting microCT images were then segmented and labeled as regions of bone trabeculae, endosteum, active marrow, and inactive marrow through application of image processing algorithms. The PIRT methodology was then implemented within the EGSNRC radiation transport code whereby electrons of various initial energies are simultaneously tracked within both the ex vivo CT macroimage and the CT microimage of the skeletal site. At initial electron energies greater than 50-200 keV, a divergence in absorbed fractions to active marrow are noted between PIRT model simulations and those estimated under existing techniques of infinite spongiosa transport. Calculations of radionuclide S values under both methodologies imply that current chord-based models may overestimate the absorbed dose to active bone marrow in these skeletal sites by 0% to 27% for low-energy beta emitters (33P, 169Er, and 177Lu), by approximately 4% to 49% for intermediate-energy beta emitters (153Sm, 186Re, and 89Sr), and by

  7. Optimization of combined temozolomide and peptide receptor radionuclide therapy (PRRT) in mice after multimodality molecular imaging studies

    NARCIS (Netherlands)

    S. Bison (Sander); J.C. Haeck (Joost); K. Bol (Karin); S. Koelewijn (Stuart); H.C. Groen (Harald); M.L. Melis (Marleen); J.F. Veenland (Jifke); M.R. Bernsen (Monique); M. de Jong (Marion)

    2015-01-01

    textabstractBackground: Successful treatments of patients with somatostatin receptor (SSTR)-overexpressing neuroendocrine tumours (NET) comprise somatostatin-analogue lutetium-177-labelled octreotate (177Lu-TATE) treatment, also referred to as peptide receptor radionuclide therapy (PRRT), and temozo

  8. Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT.

    Science.gov (United States)

    Breeman, Wouter A P; Chan, Ho Sze; de Zanger, Rory M S; Konijnenberg, Mark K; de Blois, Erik

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has become an established procedure for the treatment of patients suffering from inoperable neuroendocrine cancers over-expressing somatostatin receptors. Success of PRRT depends on the availability of the radiolabeled peptide with adequately high specific activity, so that required therapeutic efficacy can be achieved without saturating the limited number of receptors available on the target lesions. Specific activity of the radionuclide and the radiolabeled somatostatin analog are therefore an important parameters. Although these analogs have been investigated and improved, and successfully applied for PRRT for more than 15 years, there are still many possibilities for further improvements that fully exploit PRRT with 177Lu-DOTA-TATE. The here summarized data presented herein on increased knowledge of the components of 177Lu-DOTA-TATE (especially the purity of 177Lu and specific activity of 177Lu) and the reaction kinetics during labeling 177Lu-DOTA-TATE clearly show that the peptide dose and dose in GBq can be varied. Here we present an overview of the development, formulation and optimisation of 177Lu-DOTA-TATE, mainly addressing radiochemical parameters.

  9. Emergence and present status of Lu-177 in targeted radiotherapy. The Indian scenario

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, S.; Das, T.; Chakraborty, S.; Venkatesh, M. [Bhabha Atomic Reseach Centre, Trombay, Mumbai (India). Radiopharmaceuticals Div.

    2012-07-01

    {sup 177}Lu is presently considered to be a potential radionuclide for the development of agents for radionuclide therapy owing to its favorable nuclear decay characteristics [T{sub 1/2} = 6.65 d, E{sub {beta}}{sub (max)} = 0.497 MeV, E{sub {gamma}} = 113 KeV (6.4%) and 208 KeV (11%)]. While the long half-life of this promising radioisotope offers distinct logistic advantage, particularly, in countries having limited reactor facilities, the feasibility of its large-scale production with adequate specific activity and excellent radionuclidic purity in medium flux research reactors constitute yet another desirable feature. Extensive studies have been carried out to optimize the production of this isotope, with high specific activity and radionuclidic purity by the (n,{gamma}) route using the highest available flux and the optimum irradiation time. The gradual evolution of clin ical grade {sup 177}LuCl{sub 3} as a new radiochemical, ready for commercial deployment by Radiopharmaceuticals Division, Bhabha Atomic Research Centre, to nuclear medicine centers all over India was accomplished in 2010 in a stepwise manner with the commencement of the production of high specific activity {sup 177}Lu from enriched target in 2001. Research on {sup 177}Lu has demonstrated its immense potential in radiotherapeutic applications, a direct outcome of which has resulted in indigenous development of two agents viz. {sup 177}Lu-EDTMP and {sup 177}Lu-DOTA-TATE presently being evaluated in human patients for palliative care of bone pain due to skeletal metastases and treatment of malignancies of neuroendocrine origin, respectively. Using locally produced {sup 177}Lu, the radiolabeling of a plethora of other molecules with potential applicability in radiation synovectomy and targeted therapy of malignant tumors have been successfully demonstrated. A few of these agent such as a novel {sup 177}Lu-labeled porphyrin has shown considerable promise in initial studies and is presently evaluated

  10. Erectile function after radical prostatectomy: Do patients return to baseline?

    DEFF Research Database (Denmark)

    Fode, Mikkel; Frey, Anders; Jakobsen, Henrik

    2015-01-01

    PURPOSE: Patient-specific dosimetry of lutetium-177 ((177)Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts and the acti......PURPOSE: Patient-specific dosimetry of lutetium-177 ((177)Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts...... technique, the measured ratio was close to the real ratio, and the differences between spheres were small. CONCLUSION: For quantitative (177)Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated...... and the real ratio is less than 10% for both energy windows....

  11. Localization of colorectal carcinoma by rhenium-188-labeled B72.3 antibody in xenografted mice

    Energy Technology Data Exchange (ETDEWEB)

    Hosono, Masako N. [Osaka City Univ. (Japan). Medical School; Hosono, Makoto; Zamora, P.O.; Guhlke, S.; Haberberger, T.; Bender, H.; Knapp, F.F.R.; Biersack, H.J.

    1998-04-01

    In order to evaluate the feasibility of {sup 188}Re-labeled antibodies for radioimmunotargeting, monoclonal antibody B72.3, recognizing TAG-72, expressed on the surface membranes of colorectal cancer cells, was directly labeled with {sup 188}Re, obtained from a {sup 188}W/{sup 188}Re generator, using stannous tartrate and compared with {sup 125}I-labeled B72.3. As a control, a human IgG was also radiolabeled with {sup 188}Re and {sup 125}I. Prepared antibodies for {sup 188}Re labeling could be stored as kits. Biodistribution was determined in nude mice inoculated with human colorectal carcinoma LoVo. Labeling efficiency and immunoreactivity of {sup 188}Re-B72.3 were 80.3% and 64.7%, respectively. {sup 188}Re-B72.3 localized specifically in the LoVo tumors. Although the absolute tumor accumulation level of {sup 188}Re-B72.3 was lower than {sup 125}I-B72.3, {sup 188}Re-B72.3 demonstrated higher tumor-to-blood contrast than the {sup 125}I-labeled counterpart, 2.04{+-}0.44 vs. 1.05{+-}0.28 at 96 hours, because of fast clearance from the blood. {sup 188}Re-B72.3 seemed efficient for the imaging and therapy of colorectal carcinoma. (author)

  12. Comparision of {sup 188}Rhenuim-tin colloid and {sup 188}Rhenium-sulfur colloid as a radiation synovectomy agent

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Y. J.; Jung, J. M.; Kim, Y. J.; Jang, Y. S.; Lee, D. S.; Jung, J. K.; Song, Y. W.; Lee, M. C. [KAERI, Taejon (Korea, Republic of)

    1999-10-01

    Beta-emitting radiocolloids have been used for the treatment of rheumatoid arthritis. As a generator produced beta-emitting radionuclide, the importance of Re-188 for radionuclide therapy is increasing rapidly. We compared the radiochemistry of two {sup 188}Re labeled radiocolloids: {sup 188}Re-tin colloid and {sup 188}Re-sulfur colloid. {sup 188}Re-tin colloid was obtained by reacting 10 mg SnCl{sub 2}{center_dot}H{sub 2}O and {sup 188}Re perrhenate. {sup 188}Re-sulfur colloid was labeled by boiling 40 mg sodium thiosulfate, 0.8 mg Na{sub 2}{center_dot}EDTA, and 0.8 mg potassium perrhenate with {sup 188}Re perrhenate. Radiochemical purity was checked by ITLC-SG/ saline. Labeling efficiencies reached >98% for tin colloid at 2 hr and 89{approx}94% for sulfur colloid at 3 hr. All the preparations were stable for 72 hr in water, serum, and synovial fluid. If labeled at higher temperature, particle size of tin colloid increased. Remained radioactivity of {sup 188}Re-sulfur colloid in disposable polypropylene syringe after injecting to mice was high (62.0{+-}7.0%) due to its hydrophobic nature, although, tin colloid did not show high remained radioactivity (2.9{+-}1.6%). Biodistribution in Antigen induced arthratitis model rabbit after synovial space injection showed that {sup 188}Re-tin colloid was well retained in synovial space for 48 hr. Although, both {sup 188}Re-tin colloid and {sup 188}Re-sulfur colloid might be useful for radionuclide therapy, we concluded that {sup 188}Re-tin colloid is more adventageous over {sup 188}Re-sulfur colloid, due to higher labeling efficency, size-controllable property, and lower residual activity in syringe.

  13. Towards tailored radiopeptide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Radojewski, Piotr [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); Dumont, Rebecca [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); UCLA, Department of Radiology, David Geffen School of Medicine, Los Angeles, CA (United States); Marincek, Nicolas; Walter, Martin A. [University Hospital Bern, Institute of Nuclear Medicine, Bern (Switzerland); University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Brunner, Philippe; Mueller-Brand, Jan [University Hospital Basel, Institute of Nuclear Medicine, Basel (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Briel, Matthias [University Hospital Basel, Basel Institute for Clinical Epidemiology and Biostatistics, Basel (Switzerland)

    2015-07-15

    Somatostatin receptor-targeted radiopeptide therapy is commonly performed using single radioisotopes. We evaluated the benefits and harms of combining radioisotopes in radiopeptide therapy in patients with neuroendocrine tumor. Using multivariable-adjusted survival analyses and competing risk analyses we evaluated outcomes in patients with neuroendocrine tumor receiving {sup 90}Y-DOTATOC, {sup 177}Lu-DOTATOC or their combination. {sup 90}Y-DOTATOC plus {sup 177}Lu-DOTATOC treatment was associated with longer survival than {sup 90}Y-DOTATOC (66.1 vs. 47.5 months; n = 1,358; p < 0.001) or {sup 177}Lu-DOTATOC alone (66.1 vs. 45.5 months; n = 390; p < 0.001). {sup 177}Lu-DOTATOC was associated with longer survival than {sup 90}Y-DOTATOC in patients with solitary lesions (HR 0.3, range 0.1 - 0.7; n = 153; p = 0.005), extrahepatic metastases (HR 0.5, range 0.3 - 0.9; n = 256; p = 0.029) and metastases with low uptake (HR 0.1, range 0.05 - 0.4; n = 113; p = 0.001). {sup 90}Y-DOTATOC induced higher hematotoxicity rates than combined treatment (9.5 % vs. 4.0 %, p = 0.005) or {sup 177}Lu-DOTATOC (9.5 % vs. 1.4 %, p = 0.002). Renal toxicity was similar among the treatments. Using {sup 90}Y and {sup 177}Lu might facilitate tailoring radiopeptide therapy and improve survival in patients with neuroendocrine tumors. (orig.)

  14. Anti-L1CAM radioimmunotherapy is more effective with the radiolanthanide terbium-161 compared to lutetium-177 in an ovarian cancer model

    Energy Technology Data Exchange (ETDEWEB)

    Gruenberg, Juergen; Lindenblatt, Dennis; Cohrs, Susan; Fischer, Eliane [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); Dorrer, Holger [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); Zhernosekov, Konstantin [ITG Isotope Technologies Garching GmbH, Garching (Germany); Koester, Ulli [Institut Laue-Langevin, Grenoble (France); Tuerler, Andreas [Paul Scherrer Institute, Laboratory of Radiochemistry and Environmental Chemistry, Villigen (Switzerland); University of Bern, Department of Chemistry and Biochemistry, Berne (Switzerland); Schibli, Roger [Paul Scherrer Institute, Center for Radiopharmaceutical Sciences ETH-PSI-USZ, Villigen (Switzerland); ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2014-10-15

    The L1 cell adhesion molecule (L1CAM) is considered a valuable target for therapeutic intervention in different types of cancer. Recent studies have shown that anti-L1CAM radioimmunotherapy (RIT) with {sup 67}Cu- and {sup 177}Lu-labelled internalising monoclonal antibody (mAb) chCE7 was effective in the treatment of human ovarian cancer xenografts. In this study, we directly compared the therapeutic efficacy of anti-L1CAM RIT against human ovarian cancer under equitoxic conditions with the radiolanthanide {sup 177}Lu and the potential alternative {sup 161}Tb in an ovarian cancer therapy model. Tb was produced by neutron bombardment of enriched {sup 160}Gd targets. {sup 161}Tb and {sup 177}Lu were used for radiolabelling of DOTA-conjugated antibodies. The in vivo behaviour of the radioimmunoconjugates (RICs) was assessed in IGROV1 tumour-bearing nude mice using biodistribution experiments and SPECT/CT imaging. After ascertaining the maximal tolerated doses (MTD) the therapeutic impact of 50 % MTD of {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 was evaluated in groups of ten mice by monitoring the tumour size of subcutaneous IGROV1 tumours. The average number of DOTA ligands per antibody was 2.5 and maximum specific activities of 600 MBq/mg were achieved under identical radiolabelling conditions. RICs were stable in human plasma for at least 48 h. {sup 177}Lu- and {sup 161}Tb-DOTA-chCE7 showed high tumour uptake (37.8-39.0 %IA/g, 144 h p.i.) with low levels in off-target organs. SPECT/CT images confirmed the biodistribution data. {sup 161}Tb-labelled chCE7 revealed a higher radiotoxicity in nude mice (MTD: 10 MBq) than the {sup 177}Lu-labelled counterpart (MTD: 12 MBq). In a comparative therapy study with equitoxic doses, tumour growth inhibition was better by 82.6 % for the {sup 161}Tb-DOTA-chCE7 than the {sup 177}Lu-DOTA-chCE7 RIT. Our study is the first to show that anti-L1CAM {sup 161}Tb RIT is more effective compared to {sup 177}Lu RIT in ovarian cancer xenografts

  15. In vivo Evaluation of PEGylated 64Cu-liposomes with Theranostic and Radiotherapeutic Potential using Micro PET/CT

    DEFF Research Database (Denmark)

    Petersen, Anncatrine Luisa; Henriksen, Jonas Rosager; Binderup, Tina;

    2016-01-01

    The objective of this study was to evaluate the potentialof PEGylated 64Cu-liposomes in clinical diagnosticpositron emission tomography (PET) imaging andPEGylated 177Lu-liposomes in internal tumor radiotherapythrough in vivo characterization and dosimetric analysis in ahuman xenograft mouse model....... Liposomes with 5 and 10 mol% PEG were characterizedwith respect to size, charge, and 64Cu- and 177Lu-loadingefficiency. The tumor imaging potential of 64Cu-loadedliposomes was evaluated in terms of in vivo biodistribution,tumor accumulation and tumor-to-muscle (T/M) ratios, usingPET imaging. The potential...

  16. Calculation of electron and isotopes dose point kernels with fluka Monte Carlo code for dosimetry in nuclear medicine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Botta, F; Di Dia, A; Pedroli, G; Mairani, A; Battistoni, G; Fasso, A; Ferrari, A; Ferrari, M; Paganelli, G

    2011-06-01

    The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, fluka Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, fluka has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one.Methods: fluka DPKs have been calculated in both water and compact bone for monoenergetic electrons (10–3 MeV) and for beta emitting isotopes commonly used for therapy (89Sr, 90Y, 131I, 153Sm, 177Lu, 186Re, and 188Re). Point isotropic sources have been simulated at the center of a water (bone) sphere, and deposed energy has been tallied in concentric shells. fluka outcomes have been compared to penelope v.2008 results, calculated in this study as well. Moreover, in case of monoenergetic electrons in water, comparison with the data from the literature (etran, geant4, mcnpx) has been done. Maximum percentage differences within 0.8·RCSDA and 0.9·RCSDA for monoenergetic electrons (RCSDA being the continuous slowing down approximation range) and within 0.8·X90 and 0.9·X90 for isotopes (X90 being the radius of the sphere in which 90% of the emitted energy is absorbed) have been computed, together with the average percentage difference within 0.9·RCSDA and 0.9·X90 for electrons and isotopes, respectively.Results: Concerning monoenergetic electrons, within 0.8·RCSDA (where 90%–97% of the particle energy is deposed), fluka and penelope agree mostly within 7%, except for 10 and 20 keV electrons (12% in water, 8

  17. Calculation of electron and isotopes dose point kernels with fluka Monte Carlo code for dosimetry in nuclear medicine therapy

    Energy Technology Data Exchange (ETDEWEB)

    Botta, F.; Mairani, A.; Battistoni, G.; Cremonesi, M.; Di Dia, A.; Fasso, A.; Ferrari, A.; Ferrari, M.; Paganelli, G.; Pedroli, G.; Valente, M. [Medical Physics Department, European Institute of Oncology, Via Ripamonti 435, 20141 Milan (Italy); Istituto Nazionale di Fisica Nucleare (I.N.F.N.), Via Celoria 16, 20133 Milan (Italy); Medical Physics Department, European Institute of Oncology, Via Ripamonti 435, 20141 Milan (Italy); Jefferson Lab, 12000 Jefferson Avenue, Newport News, Virginia 23606 (United States); CERN, 1211 Geneva 23 (Switzerland); Medical Physics Department, European Institute of Oncology, Milan (Italy); Nuclear Medicine Department, European Institute of Oncology, Via Ripamonti 435, 2014 Milan (Italy); Medical Physics Department, European Institute of Oncology, Via Ripamonti 435, 20141 Milan (Italy); FaMAF, Universidad Nacional de Cordoba and CONICET, Cordoba, Argentina C.P. 5000 (Argentina)

    2011-07-15

    Purpose: The calculation of patient-specific dose distribution can be achieved by Monte Carlo simulations or by analytical methods. In this study, fluka Monte Carlo code has been considered for use in nuclear medicine dosimetry. Up to now, fluka has mainly been dedicated to other fields, namely high energy physics, radiation protection, and hadrontherapy. When first employing a Monte Carlo code for nuclear medicine dosimetry, its results concerning electron transport at energies typical of nuclear medicine applications need to be verified. This is commonly achieved by means of calculation of a representative parameter and comparison with reference data. Dose point kernel (DPK), quantifying the energy deposition all around a point isotropic source, is often the one. Methods: fluka DPKs have been calculated in both water and compact bone for monoenergetic electrons (10{sup -3} MeV) and for beta emitting isotopes commonly used for therapy ({sup 89}Sr, {sup 90}Y, {sup 131}I, {sup 153}Sm, {sup 177}Lu, {sup 186}Re, and {sup 188}Re). Point isotropic sources have been simulated at the center of a water (bone) sphere, and deposed energy has been tallied in concentric shells. fluka outcomes have been compared to penelope v.2008 results, calculated in this study as well. Moreover, in case of monoenergetic electrons in water, comparison with the data from the literature (etran, geant4, mcnpx) has been done. Maximum percentage differences within 0.8{center_dot}R{sub CSDA} and 0.9{center_dot}R{sub CSDA} for monoenergetic electrons (R{sub CSDA} being the continuous slowing down approximation range) and within 0.8{center_dot}X{sub 90} and 0.9{center_dot}X{sub 90} for isotopes (X{sub 90} being the radius of the sphere in which 90% of the emitted energy is absorbed) have been computed, together with the average percentage difference within 0.9{center_dot}R{sub CSDA} and 0.9{center_dot}X{sub 90} for electrons and isotopes, respectively. Results: Concerning monoenergetic electrons

  18. A preclinical simulated dataset of S-values and investigation of the impact of rescaled organ masses using the MOBY phantom

    Science.gov (United States)

    Kostou, Theodora; Papadimitroulas, Panagiotis; Loudos, George; Kagadis, George C.

    2016-03-01

    Nuclear medicine and radiation therapy, although well established, are still rapidly evolving, by exploiting animal models, aiming to define precise dosimetry in molecular imaging protocols. The purpose of the present study was to create a dataset based on the MOBY phantom for the calculation of organ-to-organ S-values of commonly used radionuclides. S-values of most crucial organs were calculated using specific biodistributions with a whole-body heterogeneous source. In order to determine the impact of the varying organs’ size on the S-values, and based on the fact that the anatomic properties of the organs are correlated with S-values, dosimetric calculations were performed by simulating the MOBY-version 2 model with different whole-body masses. The GATE Monte Carlo simulation toolkit was used for all simulations. Two mouse models of different body masses were developed to calculate the S-values of eight commonly used radioisotopes in nuclear imaging studies, namely 18F, 68Ga, 131I, 111In, 177Lu, and 99mTc, 90Y and 188Re. The impact of modified mass of the source organs in S-values was investigated with 18F, and 90Y in five different scalings of the source organs. Based on realistic preclinical exams, three mouse models, 22, 28 and 34 g, were used as input in the GATE simulator based on realistic preclinical exams to calculate the S-values of the six radioisotopes used. Whole body activity distributions were used as the source organ. The simulation procedure was validated in terms of extracting individual organ-to-organ S-values, and consequently in calculating the new S-values using a heterogeneous activity distribution as a source. The calculation was validated with 18F source in a 30 g mouse model. For the generation of the new S-values with heterogeneous activity sources, four organs were used for the calculation of a single S-value. The absorbed doses per organ were compared with previously published reports. The validation procedure of 18F indicates

  19. Current Status of Nuclear Medicine Practice in the Middle East.

    Science.gov (United States)

    Paez, Diana; Becic, Tarik; Bhonsle, Uday; Jalilian, Amir R; Nuñez-Miller, Rodolfo; Osso, Joao Alberto

    2016-07-01

    availability of (68)Ge-(68)Ga generators is increasing and studies involving prostate-specific membrane antigen or DOTA-chelated peptides or both are performed in at least seven countries. Although therapeutic radionuclide agents are mostly imported from outside the region, this does not limit the availability of therapies with (90)Y, (153)Sm, (177)Lu, (131)I, (188)Re, and (89)Sr. Nevertheless, therapies based on alpha particle emitters are still largely not available in the region and are currently only available in Israel and Turkey. Regarding human resources, according to the data provided there are 1157 NM physicians, 1953 technologists, 586 medical physicists, and 173 radiopharmacists or radiochemists in the region. Approximately half of all available human resources are accounted for by Turkey. The region has great potential for expanding the applications of NM; this becomes especially important in view of the high prevalence of non-communicable diseases. Further increasing awareness of the clinical applications of NM in healthcare and strengthening technical and human capacities including the establishment of training programs for all professionals and disciplines in the field are recognized as key components in advancing the practice of NM in the Middle East.

  20. PLGA nanoparticles for peptide receptor radionuclide therapy of neuroendocrine tumors: a novel approach towards reduction of renal radiation dose.

    Directory of Open Access Journals (Sweden)

    Geetanjali Arora

    Full Text Available BACKGROUND: Peptide receptor radionuclide therapy (PRRT, employed for treatment of neuroendocrine tumors (NETs is based on over-expression of Somatostatin Receptors (SSTRs on NETs. It is, however, limited by high uptake and retention of radiolabeled peptide in kidneys resulting in unnecessary radiation exposure thus causing nephrotoxicity. Employing a nanocarrier to deliver PRRT drugs specifically to the tumor can reduce the associated nephrotoxicity. Based on this, (177Lu-DOTATATE loaded PLGA nanoparticles (NPs were formulated in the present study, as a potential therapeutic model for NETs. METHODOLOGY AND FINDINGS: DOTATATE was labeled with Lutetium-177 ((177Lu (labeling efficiency 98%; R(f∼0.8. Polyethylene Glycol (PEG coated (177Lu-DOTATATE-PLGA NPs (50:50 and 75:25 formulated, were spherical with mean size of 304.5±80.8 and 733.4±101.3 nm (uncoated and 303.8±67.2 and 494.3±71.8 nm (coated for PLGA(50:50 and PLGA(75:25 respectively. Encapsulation efficiency (EE and In-vitro release kinetics for uncoated and coated NPs of PLGA (50:50 & 75:25 were assessed and compared. Mean EE was 77.375±4.98% & 67.885±5.12% (uncoated and 65.385±5.67% & 58.495±5.35% (coated. NPs showed initial burst release between 16.64-21.65% with total 42.83-44.79% over 21 days. The release increased with coating to 20.4-23.95% initially and 60.97-69.12% over 21 days. In-vivo studies were done in rats injected with (177Lu-DOTATATE and (177Lu-DOTATATE-NP (uncoated and PEG-coated by imaging and organ counting after sacrificing rats at different time points over 24 hr post-injection. With (177Lu-DOTATATE, renal uptake of 37.89±10.2%ID/g was observed, which reduced to 4.6±1.97% and 5.27±1.66%ID/g with uncoated and coated (177Lu-DOTATATE-NP. The high liver uptake with uncoated (177Lu-DOTATATE-NP (13.68±3.08% ID/g, reduced to 7.20±2.04%ID/g (p = 0.02 with PEG coating. CONCLUSION: PLGA NPs were easily formulated and modified for desired release properties. PLGA

  1. Intra-arterial injection of lipid nano-capsules charged in rhenium-188, for the treatment of hepatocellular carcinomas among the rat; Injection intra-arterielle de nanocapsules lipidiques chargees en rhenium-188, pour le traitement des carcinomes hepatocellulaires chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Vanpouille, C.; Lacoeuille, F.; Hindre, F. [Inserm U646, Angers, (France); Roux, J. [service commun animalerie, hospitalo-universitaire, Angers, (France); Aube, C. [service de radiologie, CHU d' Angers, (France); Oberti, F. [service de gastro-enterologie et hepatologie, CHU d' Angers, (France); Lejeune, J.J.; Couturier, O. [service de medecine nucleaire, CHU d' Angers, (France)

    2009-05-15

    The objective of this study was to evaluate the therapy efficiency of the {sup 188}Re incorporated in the middle of lipid capsules (N.C.L. {sup 188}Re-S.S.S.) on a hepato carcinoma model of rat. The preliminary results are encouraging and show the efficiency of a single injection of N.C.L.{sup 188}Re-S.S.S. in a hepato carcinoma model of rat. (N.C.)

  2. Evaluation of Cobalt-Labeled Octreotide Analogs for Molecular Imaging and Auger Electron-Based Radionuclide Therapy

    DEFF Research Database (Denmark)

    Thisgaard, Helge; Olsen, Birgitte Brinkmann; Dam, Johan Hygum;

    2014-01-01

    )Co-DOTATATE via DNA double-strand break and proliferation assays. Comparisons with the therapeutic effects of (111)In- and (177)Lu-DOTATATE were also performed. Tumor uptake and normal tissue uptake were characterized in a subcutaneous pancreatic tumor mouse model. RESULTS: All 3 cobalt-conjugated peptides...

  3. Reduction of renal uptake of radiolabeled octreotate by amifostine coadministration

    NARCIS (Netherlands)

    M.L. Melis (Marleen); R. Valkema (Roelf); E.P. Krenning (Eric); M. de Jong (Marcel)

    2012-01-01

    textabstractMegalin-mediated renal retention of radiolabeled somatostatin analogs may lead to nephrotoxicity during peptide receptor radionuclide therapy (PRRT). The cytoprotective agent amifostine protected rats from long-term nephrotoxicity after PRRT with 177Lu-DOTA,Tyr3-octreotate. This study de

  4. Comparison of ⁹⁰Y and ¹⁷⁷Lu measurement capability in UK and European hospitals.

    Science.gov (United States)

    Fenwick, Andrew; Baker, Michaela; Ferreira, Kelley; Keightley, John

    2014-05-01

    Comparison exercises involving (90)Y and (177)Lu were performed during 2009 and 2012, respectively, to assess the measurement capability of hospitals in the UK and Europe. The results from the measurement of a typical liquid solution of (90)Y show that only 40% of participants could measure the solution to within 5% of the certificated value and that a significant -6% bias was present due to the use of non-standard geometries for the calibration of equipment. The results from the measurement of a standard liquid solution of (177)Lu show that 81% of participants could measure to within 5% of the certificated value and in fact 65% of these results were within 2% of the certificated value, showing administered activities can be far more accurately measured for (177)Lu than for (90)Y and that (177)Lu has a far smaller geometry dependence. These studies were performed to identify specific measurement issues in the user community and to identify areas where future research should be focused. In addition to this the work allows the participants to adjust measurement practice and identify key measurement issues.

  5. In vivo evaluation of PEGylated {sup 64}Cu-liposomes with theranostic and radiotherapeutic potential using micro PET/CT

    Energy Technology Data Exchange (ETDEWEB)

    Petersen, Anncatrine Luisa; Andresen, Thomas Lars [Technical University of Denmark, Department of Micro- and Nanotechnology, Lyngby (Denmark); Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Henriksen, Jonas Rosager [Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Technical University of Denmark, Department of Chemistry, Lyngby (Denmark); Binderup, Tina; Hag, Anne Mette; Kjaer, Andreas [University of Copenhagen, Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet and Cluster for Molecular Imaging, Faculty of Health Sciences, Copenhagen (Denmark); Elema, Dennis Ringkjoebing [Technical University of Denmark, Center for Nanomedicine and Theranostics, Lyngby (Denmark); Technical University of Denmark, Center for Nuclear Technologies, Hevesy Laboratory, Roskilde (Denmark); Rasmussen, Palle Hedengran [Technical University of Denmark, Center for Nuclear Technologies, Hevesy Laboratory, Roskilde (Denmark)

    2016-05-15

    The objective of this study was to evaluate the potential of PEGylated {sup 64}Cu-liposomes in clinical diagnostic positron emission tomography (PET) imaging and PEGylated {sup 177}Lu-liposomes in internal tumor radiotherapy through in vivo characterization and dosimetric analysis in a human xenograft mouse model. Liposomes with 5 and 10 mol% PEG were characterized with respect to size, charge, and {sup 64}Cu- and {sup 177}Lu-loading efficiency. The tumor imaging potential of {sup 64}Cu-loaded liposomes was evaluated in terms of in vivo biodistribution, tumor accumulation and tumor-to-muscle (T/M) ratios, using PET imaging. The potential of PEGylated liposomes for diagnostic and therapeutic applications was further evaluated through dosimetry analysis using OLINDA/EXM software. The {sup 64}Cu-liposomes were used as biological surrogates to estimate the organ and tumor kinetics of {sup 177}Lu-liposomes. High remote loading efficiency (>95 %) was obtained for both {sup 64}Cu and {sup 177}Lu radionuclides with PEGylated liposomes, and essentially no leakage of the encapsulated radionuclide was observed upon storage and after serum incubation for 24 h at 37 C. The 10 mol% PEG liposomes showed higher tumor accumulation (6.2 ± 0.2 %ID/g) than the 5 mol% PEG liposomes, as evaluated by PET imaging. The dosimetry analysis of the {sup 64}Cu-liposomes estimated an acceptable total effective dose of 3.3.10{sup -2} mSv/MBq for diagnostic imaging in patients. A high absorbed tumor dose (114 mGy/MBq) was estimated for the potential radiotherapeutic {sup 177}Lu-liposomes. The overall preclinical profile of PEGylated {sup 64}Cu-liposomes showed high potential as a new PET theranostic tracer for imaging in humans. Dosimetry results predicted that initial administered activity of 200 MBq of {sup 64}Cu-liposomes should be acceptable in patients. Work is in progress to validate the utility of PEGylated {sup 64}Cu-liposomes in a clinical research programme. The high absorbed tumor dose

  6. Comparative therapeutic efficacy of rhenium-188 radiolabeled-liposome and 5-fluorouracil in LS-174T human colon carcinoma solid tumor xenografts.

    Science.gov (United States)

    Hsu, Chin-Wei; Chang, Ya-Jen; Chang, Chih-Hsien; Chen, Liang-Cheng; Lan, Keng-Li; Ting, Gann; Lee, Te-Wei

    2012-10-01

    Nanoliposomes are important carriers capable of packaging drugs for various delivery applications. Rhenium-188-radiolabeled liposome ((188)Re-liposome) has potential for radiotherapy and diagnostic imaging. To evaluate the targeting of (188)Re-liposome, biodistribution, microSPECT/CT, whole-body autoradiography (WBAR), and pharmacokinetics were performed in LS-174T human tumor-bearing mice. The comparative therapeutic efficacy of (188)Re-liposome and 5-fluorouracil (5-FU) was assessed according to inhibition of tumor growth and the survival ratio. The highest uptake of (188)Re-liposome in LS-174T tumor was found at 24 hours by biodistribution and microSPECT/CT imaging, showing a positive correlation for tumor targeting of (188)Re-liposome using the Pearson's correlation analysis (r=0.997). Pharmacokinetics of (188)Re-liposome showed the properties of high circulation time and high bioavailability (mean residence time [MRT]=18.8 hours, area under the curve [AUC]=1371%ID/g·h). For therapeutic efficacy, the tumor-bearing mice treated with (188)Re-liposome (80% maximum tolerated dose [MTD], 23.7 MBq) showed better tumor growth inhibition and longer survival time than those treated with 5-FU (80% MTD, 144 mg/kg). The median survival time for mice treated with (188)Re-liposome (58.5 days; p0.05) and normal saline-treated mice (43.63 days). Dosimetry study revealed that the (188)Re-liposome did not lead to high absorbed doses in normal tissue, but did in small tumors. These results of imaging and biodistribution indicated the highly specific accumulation of tumor after intravenous (i.v.) injection of (188)Re-liposome. The therapeutic efficacy of radiotherapeutics of (188)Re-liposome have been confirmed in a LS-174T solid tumor animal model, which points to the potential benefit and promise of passive nanoliposome delivered radiotherapeutics for cancer treatment.

  7. Peptide Receptor Radionuclide Therapy with radiolabelled somatostatin analogues in patients with somatostatin receptor positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Essen, Martijn van; Krenning, Eric P.; Jong, Marion De; Valkema, Roelf; Kwekkeboom, Dik J. [Dept. of Nuclear Medicine, Erasmus MC, ' s Gravendijkwal 230, Rotterdam (Netherlands)

    2007-08-15

    Peptide Receptor Radionuclide Therapy (PRRT) with radiolabelled somatostatin analogues is a promising treatment option for patients with inoperable or metastasised neuroendocrine tumours. Symptomatic improvement may occur with all of the various {sup 111}In, {sup 90}Y, or {sup 177}Lu-labelled somatostatin analogues that have been used. Since tumour size reduction was seldom achieved with {sup 111}Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like {sup 90}Y and {sup 177}Lu were developed. Reported anti-tumour effects of [{sup 90}Y-DOTA0,Tyr3]octreotide vary considerably between various studies: Tumour regression of 50% or more was achieved in 9 to 33% (mean 22%). With [{sup 177}Lu-DOTA0,Tyr3]octreotate treatments, tumour regression of 50% or more was achieved in 28% of patients and tumour regression of 25 to 50% in 19% of patients, stable disease was demonstrated in 35% and progressive disease in 18%. Predictive factors for tumour remission were high tumour uptake on somatostatin receptor scintigraphy and limited amount of liver metastases. The side-effects of PRRT are few and mostly mild, certainly when using renal protective agents: Serious side-effects like myelodysplastic syndrome or renal failure are rare. The median duration of the therapy response for [{sup 90}Y-DOTA0,Tyr3]octreotide and [{sup 177}Lu-DOTA0,Tyr3]octreotate is 30 months and more than 36 months respectively. Lastly, quality of life improves significantly after treatment with [{sup 177}Lu-DOTA0,Tyr3]octreotate. These data compare favourably with the limited number of alternative treatment approaches, like chemotherapy. If more widespread use of PRRT is possible, such therapy might become the therapy of first choice in patients with metastasised or inoperable gastroenteropancreatic neuroendocrine tumours. Also the role in somatostatin receptor expressing non-GEP tumours, like metastasised paraganglioma/pheochromocytoma and non

  8. Lutetium-177 DOTATATE Production with an Automated Radiopharmaceutical Synthesis System

    Directory of Open Access Journals (Sweden)

    Alireza Aslani

    2015-07-01

    Full Text Available Objective(s: Peptide Receptor Radionuclide Therapy (PRRT with yttrium-90 (90Y and lutetium-177 (177Lu-labelled SST analogues are now therapy option for patients who have failed to respond to conventional medical therapy. In-house production with automated PRRT synthesis systems have clear advantages over manual methods resulting in increasing use in hospital-based radiopharmacies. We report on our one year experience with an automated radiopharmaceutical synthesis system.Methods: All syntheses were carried out using the Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® automated synthesis system. All materials and methods used were followed as instructed by the manufacturer of the system (Eckert & Ziegler Eurotope, Berlin, Germany. Sterile, GMP-certified, no-carrier added (NCA 177Lu was used with GMPcertifiedpeptide. An audit trail was also produced and saved by the system. The quality of the final product was assessed after each synthesis by ITLCSG and HPLC methods.Results: A total of 17 [177Lu]-DOTATATE syntheses were performed between August 2013 and December 2014. The amount of radioactive [177Lu]-DOTATATE produced by each synthesis varied between 10-40 GBq and was dependant on the number of patients being treated on a given day. Thirteen individuals received a total of 37 individual treatment administrations in this period. There were no issues and failures with the system or the synthesis cassettes. The average radiochemical purity as determined by ITLC was above 99% (99.8 ± 0.05% and the average radiochemical purity as determined by HPLC technique was above 97% (97.3 ± 1.5% for this period.Conclusions: The automated synthesis of [177Lu]-DOTATATE using Eckert & Ziegler Eurotope’s Modular-Lab Pharm Tracer® system is a robust, convenient and high yield approach to the radiolabelling of DOTATATE peptide benefiting from the use of NCA 177Lu and almost negligible radiation exposure of the operators.

  9. Use of the ORNL Tungsten-188/Rhenium-188 Generator for Preparation of the Rhenium-188 HDD/Lipiodol Complex for Transarterial Liver Cancer Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Knapp Jr, Russ F [ORNL; Jeong, J M [Seoul National University

    2008-01-01

    This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ({sup 188}W)/rhenium-188 ({sup 188}Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the {sup 188}Re-perrhenate bolus and preparation of {sup 188}Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The {sup 188}W/{sup 188}Re generator has a long useful shelf-life of several months and is a convenient on-site {sup 188}Re production system. {sup 188}Re has excellent therapeutic and imaging properties (T{sub 1/2} 16.9 hours; E{beta}{sub max} 2.12 MeV; 155-keV gamma ray, 15%) and is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of {sup 188}Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of {sup 188}Re, several {sup 188}Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. {sup 188}Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of {sup 188}Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) {sup 188}W/{sup 188}Re generators. The handling of such high levels of {sup 188}Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (ie, 'As Low As Reasonably Achievable') principles must be followed. The ORNL generator provides consistently high {sup 188}Re yields (>75%) and low {sup 188}W parent breakthrough (<10{sup -3}%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require

  10. Use of the Oak Ridge National Laboratory tungsten-188/rhenium-188 generator for preparation of the rhenium-188 HDD/lipiodol complex for trans-arterial liver cancer therapy

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, J M [Seoul National University; Knapp Jr, Russ F [ORNL

    2008-01-01

    This work describes the installation, use, and quality control (QC) of the alumina-based tungsten-188 ({sup 188}W)/rhenium-188 ({sup 188}Re) generators provided by the Oak Ridge National Laboratory (ORNL). In addition, methods used for concentration of the {sup 188}Re-perrhenate bolus and preparation of {sup 188}Re-labeled HDD (4-hexadecyl-2,2,9,9-tetramethyl-4,7-diaza-1,10-decanethiol) for trans-arterial administration for therapy of nonresectable liver cancer also are described. The {sup 188}W/{sup 188}Re generator has a long useful shelf-life of several months and is a convenient on-site {sup 188}Re production system. {sup 188}Re has excellent therapeutic and imaging properties (T{sub 1/2} 16.9 hours; E{sub {beta}max} 2.12 MeV; 155-keV gamma ray, 15%) and is cost effectively obtained on demand by saline elution of the generator. The clinical efficacy of a variety of {sup 188}Re-labeled agents has been demonstrated for several therapeutic applications. Because of the favorable physical properties of {sup 188}Re, several {sup 188}Re-labeled agents are being developed and evaluated for the treatment of nonresectable/refractory liver cancer. {sup 188}Re-labeled HDD has been the most widely studied of these agents for this application and has been introduced into clinical trials at a number of institutions. The trans-arterial administration of {sup 188}Re-labeled agents for treatment of inoperable liver cancer requires use of high-level (1-2 Ci) {sup 188}W/{sup 188}Re generators. The handling of such high levels of {sup 188}Re imposes radiological precautions normally not encountered in a radiopharmacy and adequate care and ALARA (i.e., 'As Low As Reasonably Achievable') principles must be followed. The ORNL generator provides consistently high {sup 188}Re yields (>75%) and low {sup 188}W parent breakthrough (<10{sup -3}%) over an extended shelf-life of several months. However, the high elution volumes (20-40 mL for 1-2 Ci generators) can require

  11. New peptide receptor radionuclide therapy of invasive cancer cells: in vivo studies using 177Lu-DOTA-AE105 targeting uPAR in human colorectal cancer xenografts

    DEFF Research Database (Denmark)

    Persson, Morten; Rasmussen, Palle; Madsen, Jacob;

    2012-01-01

    -of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. MethodsA DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29...... by recording mouse weight and by H&E staining of kidneys in each treatment group. ResultsuPAR-positive HT-29 xenograft was clearly visualized by PET/CT imaging using 64Cu-DOTA-AE105. Subsequently, these xenograft transplants were locally irradiated using 177Lu-DOTA-AE105, where a significant effect on tumor...... size and the number of uPAR-positive cells in the tumor was found (p

  12. Nuclear medicine program progress report for quarter ending September 30, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Knapp, F.F. Jr.; Ambrose, K.R.; Beets, A.L.; Luo, H.; McPherson, D.W.; Mirzadeh, S.

    1995-12-31

    In this report, we describe the results for study of the production of lutetium-177 ({sup 177}Lu) in the High Flux Isotope Reactor (HFIR). Two pathways for production of {sup 177}Lu were studied which involved both direct neutron capture on enriched {sup 176}Lu, {sup 176}Lu (n,{gamma}){sup 177}Lu, reaction and by decay of ytterbium-177 ({sup 177}Yb) produced by the {sup 176}Yb(n,{gamma}){sup 177}Yb ({beta}{sup {minus}} {sup {yields}}) reaction. Although the direct route is more straight forward and does not involve any separation steps, the indirect method via {beta}{sup {minus}}-decay of {sup 177}Yb has the advantage of providing carrier-free {sup 177}Lu, which would be required for antibody radiolabeling and other applications where very high specific activity is required.Substrates required for preparation of tissue-specific agents and several radioisotopes were also provided during this period through several Medical Cooperative Programs. These include the substrate for preparation of the ``BMIPP`` cardiac imaging which was developed in the ORNL Nuclear Medicine Program, which was provided to Dr. A. Giodamo, M.D. and colleagues at the Catholic University Hospital in Rome, Italy. Tungsten-188 produced in the ORNL HFIR was also provided to the Catholic University Hospital for fabrication of a tungsten-188/rhenium-188 generator to provide carrier-free rhenium-188 which will be used for preparation of rhenium-188 labeled methylenediphosphonate (MDP) for initial clinical evaluation for palliative treatment of bone pain (L. Troncone, M.D.). Samples of substrates for preparation of the new ORNL ``IQNP`` agent for imaging of muscarinic-cholinergic receptors were provided to the Karolinska Institute in Stockholm, Sweden, for preparation of radioiodinated IQNP for initial imaging studies with this new agent in monkeys and for tissue binding studies with human brain samples obtained from autopsy (C. Halldin, Ph.D.).

  13. Peptide receptor radionuclide therapy in the management of gastrointestinal neuroendocrine tumors: efficacy profile, safety, and quality of life

    Science.gov (United States)

    Severi, Stefano; Grassi, Ilaria; Nicolini, Silvia; Sansovini, Maddalena; Bongiovanni, Alberto; Paganelli, Giovanni

    2017-01-01

    Peptide receptor radionuclide therapy (PRRT), developed over the last two decades, is carried out using radiopharmaceuticals such as 90Y-DOTA-Tyr3-octreotide and 177Lu-DOTA-Tyr3-octreotate (177Lu-Dotatate). These radiocompounds are obtained by labeling a synthetic somatostatin analog with a β-emitting radioisotope. The compounds differ from each other in terms of their energetic features (due to the radionuclide) and peptide receptor affinity (due to the analog) but share the common characteristic of binding specific membrane somatostatin receptors that are (generally) overexpressed in neuroendocrine neoplasms (NENs) and their metastases. NENs are tumors arising from diffuse neuroendocrine system cells that are classified according to grading based on Ki67 percentage values (Grades 1 and 2 are classed as neuroendocrine tumors [NETs]) and to the anatomical site of occurrence (in this paper, we only deal with gastroenteropancreatic [GEP]-NETs, which account for 60%–70% of all NENs). They are also characterized by specific symptoms such as diarrhea and flushing (30% of cases). Despite substantial experience gained in the area of PRRT and its demonstrable effects in terms of efficacy, safety, and improvement in quality of life, these compounds are still not registered (registration of 177Lu-Dotatate for the treatment of midgut NETs is expected soon). Thus, PRRT can only be used in experimental protocols. We provide an overview of the work of leading groups with wide-ranging experience and continuity in data publication in the area of GEP-NET PRRT and report our own personal experience of using different dosage schedules based on the presence of kidney and bone marrow risk factors. Our results on the retreatment of patients previously administered 90Y-DOTA-Tyr3-octreotide with a low dosage of 177Lu-Dotatate are also included. A comment on potential future developments of PRRT in GEP-NETs is provided. PMID:28203088

  14. Synthesis and evaluation of novel bifunctional chelating agents based on 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid for radiolabeling proteins

    Energy Technology Data Exchange (ETDEWEB)

    Chappell, L.L.; Ma, D.; Milenic, D.E.; Garmestani, K.; Venditto, V.; Beitzel, M.P.; Brechbiel, M.W. E-mail: martinwb@mail.nih.gov

    2003-08-01

    Detailed synthesis of the bifunctional chelating agents 2-methyl-6-(p-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10 -tetraacetic acid (1B4M-DOTA) and 2-(p-isothiocyanatobenzyl)-5, 6-cyclohexano-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetate (CHX-DOTA) are reported. These chelating agents were compared to 2-(p-isothiocyanatobenzyl)-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (C-DOTA) and 1, 4, 7, 10-Tetraaza-N-(1-carboxy-3-(4-nitrophenyl)propyl)-N', N'', N'''-tris(acetic acid) cyclododecane (PA-DOTA) as their {sup 177}Lu radiolabeled conjugates with Herceptin{sup TM}. In vitro stability of the immunoconjugates radiolabeled with {sup 177}Lu was assessed by serum stability studies. The in vivo stability of the radiolabeled immunoconjugates and their targeting characteristics were determined by biodistribution studies in LS-174T xenograft tumor-bearing mice. Relative radiolabeling rates and efficiencies were determined for all four immunoconjugates. Insertion of the 1B4M moiety into the DOTA backbone increases radiometal chelation rate and provides complex stability comparable to C-DOTA and PA-DOTA while the CHX-DOTA appears to not form as stable a {sup 177}Lu complex while exhibiting a substantial increase in formation rate. The 1B4M-DOTAmay have potential for radioimmunotherapy applications. Published by Elsevier Inc. All rights reserved.

  15. Long-term tolerability of PRRT in 807 patients with neuroendocrine tumours: the value and limitations of clinical factors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, Lisa; Grana, Chiara M. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Kidd, Mark; Drozdov, Ignat; Lepensky, Christopher; Modlin, Irvin M. [Yale School of Medicine, Department of Surgery, New Haven, CT (United States); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Cremonesi, Marta [European Institute of Oncology, Division of Medical Physics, Milan (Italy); Kwekkeboom, Dik J.; Krenning, Eric P. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam (Netherlands); Baum, Richard P. [Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotheraphy and Molecular Imaging, Bad Berka (Germany)

    2015-01-15

    Peptide receptor radionuclide therapy (PRRT) with {sup 90}Y and {sup 177}Lu provides objective responses in neuroendocrine tumours, and is well tolerated with moderate toxicity. We aimed to identify clinical parameters predictive of long-term renal and haematological toxicity (myelodysplastic syndrome and acute leukaemia). Of 807 patients studied at IEO-Milan (1997-2013), 793 (98 %) received {sup 177}Lu (278, 34.4 %), {sup 90}Y (358, 44.4 %) or {sup 177}Lu and {sup 90}Y combined (157. 19.5 %), and 14 (2 %) received combinations of PRRT and other agents. Follow-up was 30 months (1-180 months). The parameters evaluated included renal risk factors, bone marrow toxicity and PRRT features. Data analysis included multiple regression, random forest feature selection, and recursive partitioning and regression trees. Treatment with {sup 90}Y and {sup 90}Y + {sup 177}Lu was more likely to result in nephrotoxicity than treatment with {sup 177}Lu alone (33.6 %, 25.5 % and 13.4 % of patients, respectively; p < 0.0001). Nephrotoxicity (any grade), transient and persistent, occurred in 279 patients (34.6 %) and was severe (grade 3 + 4) in 12 (1.5 %). In only 20-27 % of any nephrotoxicity was the disease modelled by risk factors and codependent associations (p < 0.0001). Hypertension and haemoglobin toxicity were the most relevant factors. Persistent toxicity occurred in 197 patients (24.3 %). In only 22-34 % of affected patients was the disease modelled by the clinical data (p < 0.0001). Hypertension (regression coefficient 0.14, p < 0.0001) and haemoglobin toxicity (regression coefficient 0.21, p < 0.0001) were pertinent factors. Persistent toxicity was associated with shorter PRRT duration from the first to the last cycle (mean 387 vs. 658 days, p < 0.004). Myelodysplastic syndrome occurred in 2.35 % of patients (modelled by the clinical data in 30 %, p < 0.0001). Platelet toxicity grade (2.05 ± 1.2 vs. 0.58 ± 0.8, p < 0.0001) and longer PRRT duration (22.6 ± 24 vs. 15.5

  16. Long-term results of PRRT in advanced bronchopulmonary carcinoid

    Energy Technology Data Exchange (ETDEWEB)

    Mariniello, Annapaola; Bodei, Lisa; Baio, Silvia Melania; Gilardi, Laura; Colandrea, Marzia; Papi, Stefano; Grana, Chiara Maria [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); Tinelli, Carmine [IRCCS Foundation Policlinico San Matteo, Epidemiology and Biometric Unit, Pavia (Italy); Valmadre, Giuseppe [Presidio Ospedaliero E. Morelli AOVV, Sondalo (Italy); Fazio, Nicola [European Institute of Oncology, Unit of Gastrointestinal Medical Oncology and Neuroendocrine Tumors, Milan (Italy); Galetta, Domenico [European Institute of Oncology, Thoracic Surgery Division, Milan (Italy); Paganelli, Giovanni [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy)

    2016-03-15

    Peptide receptor radionuclide therapy (PRRT) for the treatment of neuroendocrine tumours (NET) has been explored for almost two decades, but there are still few trials that have exclusively investigated well-differentiated and moderately differentiated NET arising from the respiratory tree. Thus, the aim of this study was to explore the outcome in patients affected by bronchopulmonary carcinoid (BPC) following PRRT. We retrospectively analysed 114 patients with advanced stage BPC consecutively treated with PRRT at the European Institute of Oncology, Milan, from 1997 to 2012 and followed until October 2014. The objective responses, overall survival (OS) and progression-free survival (PFS) were rated, and three different PRRT protocols ({sup 90}Y-DOTATOC vs. {sup 177}Lu-DOTATATE vs. {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE) were compared with regard to their efficacy and tolerability. The median OS (evaluated in 94 of the 114 patients) was 58.8 months. The median PFS was 28.0 months. The {sup 177}Lu-DOTATATE protocol resulted in the highest 5-year OS (61.4 %). Morphological responses (partial responses + minor responses) were obtained in 26.5 % of the cohort and were associated with longer OS and PFS. The {sup 90}Y-DOTATOC + {sup 177}Lu-DOTATATE protocol provided the highest response rate (38.1 %). Adverse events were mild in the majority of patients. However, haematological toxicity negatively affected survival. No severe (grade 3/4) serum creatinine increase was observed. Patients treated with {sup 90}Y-DOTATOC alone more frequently showed a mild/moderate decrease in renal function. In patients treated with chemotherapy before PRRT had a shorter OS and PFS, and a higher risk of developing nephrotoxicity. In a large cohort of patients with advanced BPC treated in a ''real-world'' scenario and followed up for a median of 45.1 months (range 2 - 191 months), PRRT proved to be promising in prolonging survival and delaying disease progression. Despite

  17. Safety and Efficacy of 188-Rhenium-Labeled Antibody to Melanin in Patients with Metastatic Melanoma

    Directory of Open Access Journals (Sweden)

    M. Klein

    2013-01-01

    Full Text Available There is a need for effective “broad spectrum” therapies for metastatic melanoma which would be suitable for all patients. The objectives of Phase Ia/Ib studies were to evaluate the safety, pharmacokinetics, dosimetry, and antitumor activity of 188Re-6D2, a 188-Rhenium-labeled antibody to melanin. Stage IIIC/IV metastatic melanoma (MM patients who failed standard therapies were enrolled in both studies. In Phase Ia, 10 mCi 188Re-6D2 were given while unlabeled antibody preload was escalated. In Phase Ib, the dose of 188Re-6D2 was escalated to 54 mCi. SPECT/CT revealed 188Re-6D2 uptake in melanoma metastases. The mean effective half-life of 188Re-6D2 was 12.4 h. Transient HAMA was observed in 9 patients. Six patients met the RECIST criteria for stable disease at 6 weeks. Two patients had durable disease stabilization for 14 weeks and one for 22 weeks. Median overall survival was 13 months with no dose-limiting toxicities. The data demonstrate that 188Re-6D2 was well tolerated, localized in melanoma metastases, and had antitumor activity, thus warranting its further investigation in patients with metastatic melanoma.

  18. A production method for Cr-51 at IEN's cyclotron

    Energy Technology Data Exchange (ETDEWEB)

    Bastos, M.A.V.; Britto, J.L.Q. de; Vinagre, U.M.; Silva, A.G. da (Instituto de Engenharia Nuclear, Rio de Janeiro (Brazil). Dept. de Fisica)

    1990-01-01

    Thick target yields for the reactions {sup 51}V(p,n){sup 51}Cr and {sup 51}V(d,2n){sup 51}Cr were measured and compared with literature values. The excitation function for the {sup 51}V(p,n){sup 51}Cr reaction was also measured. A method for the production and separation of this radioisotope was developed via the {sup 51}V(p,n){sup 51}Cr reaction and a combination of Fe{sup +3} coprecipitation and an anion exchange technique using a Dowex 1X8 (100-200 mesh) resin in hydrochloric acid medium. (orig.).

  19. Avidin chase reduces side effects of radioimmunotherapy in nude mice bearing human colon carcinoma

    Institute of Scientific and Technical Information of China (English)

    Gui-Ping Li; Yong-Xian Wang; Kai Huang; Hui Zhang; Chun-Fu Zhang

    2005-01-01

    AIM: To evaluate the influence of avidin chase on the side effects of radioimmunotherapy (RIT) in nude mice bearing human colon carcinoma and therapeutic outcome.METHODS: Purified anti-CEA monoclonal antibody (McAb)was biotinylated with NHS-biotin, and then radiolabeled with 188Re by the direct method. 188Re-labeledbiotinylated anti-CEA McAb (188Re-CEA McAb-Bt) was intravenously injected followed by intravenous injection of avidin after 24 h. SPECT imaging and biodistribution study were performed at 28-48 h after the injection of 188Re-CEA McAb-Bt. Three groups of nude mice subcutaneously grafted with human colon carcinoma were treated 7 d after the graft. Mice in the avidin chase group received intravenous injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg) followed by intravenous injection of cold avidin (80 μg) after 24 h. Mice in the control group (treated group without avidin chase) only received the injection of 188Re-CEA McAb-Bt (11.1 MBq/20 μg), another control group (non-treated group) only received 0.1 mL normal saline solution. Toxicity was evaluated on the basis of change of body weight and peripheral WBC counts, and therapy effects were determined by variation in tumor volume. Histological analysis of tumors was also performed.RESULTS: Avidin chase markedly accelerated the clearance of 188Re-CEA McAb-Bt from the blood and normal tissues. The tumor uptakes of 188Re-CEA Mc Ab-Bt at 28 h were 5.90 and 6.42% ID/g, respectively, in chase group and in non-chase group, while the tumor-to-background (T/NT) ratios were 3.19 and 0.56, respectively. The tumor uptake was slightly decreased by avidin chase, but the T/NT ratios were increased. In treated groups the growth rate of body weight and the number of WBC decreased after injection of 188Re-CEA McAb-Bt, and the WBC counts recovered earlier in the group with avidin chase than in the group without avidin chase. Compared to the nontreated group, treated groups with and without avidin chase showed significant anti

  20. Pentavalent rhenium-188 dimercaptosuccinic acid for targeted radiotherapy: synthesis and preliminary animal and human studies

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J. [Nuclear Medicine Department, Kent and Canterbury Hospital, Canterbury (United Kingdom)]|[Department of Biosciences, University of Kent, Canterbury (United Kingdom); Lam, A.S.K. [Department of Biosciences, University of Kent, Canterbury (United Kingdom); O`Doherty, M.J.; Kettle, A.G.; Coakley, A.J. [Nuclear Medicine Department, Kent and Canterbury Hospital, Canterbury (United Kingdom); Knapp, F.F. Jr. [Nuclear Medicine Group, Oak Ridge National Laboratory (ORNL), Oak Ridge, Tenn. (United States)

    1998-06-01

    The aim of this study was to develop the kit-based synthesis of the agent on a therapeutic scale, to assess its stability in vivo, and to obtain preliminary biodistribution and dosimetry estimates, prior to evaluation of its potential as a targeted radiotherapy agent. The organ distribution of {sup 188}Re in mice was determined 2 h after injection of 3 MBq {sup 188}Re(V)DMSA prepared from eluate from a {sup 188}W/{sup 188}Re generator. Three patients with cancer of the prostate and three with cancer of the bronchus, all with bone metastases, were given 370 MBq {sup 188}Re(V)DMSA and imaged at 3 h and 24 h using the 155-keV {gamma}-photon (15%). Blood and urine samples were collected to determine clearance and to analyse the speciation of {sup 188}Re. Organ residence times were estimated from the scans, and used to estimate radiation doses using MIRDOSE 3. In mice, {sup 188}Re(V)DMSA was selective for bone and kidney. In patients, it showed selectivity for bone metastases (particularly those from prostate carcinoma) and kidney, but uptake in normal bone was not significantly greater than in surrounding soft tissues. Of the normal tissues the kidneys received the highest radiation dose (0.5-1.3 mGy/MBq). The images were strongly reminiscent of {sup 99m}Tc(V)DMSA scans in similar patients. High-performance liquid chromatography analysis of blood and urine showed no evidence of {sup 188}Re in any chemical form other than {sup 188}Re(V)DMSA up to 24 h. In conclusion, {sup 188}Re(V)DMSA and its {sup 186}Re analogue warrant further clinical assessment as generator/kit-derived agents for treatment of painful bone metastases. These agents should also be assessed in medullary thyroid carcinoma and other soft tissue tumours which have been shown to accumulate {sup 99m}Tc(V)DMSA.(orig./MG) (orig.) With 10 figs., 1 tab., 34 refs.

  1. Multi-functional system of radiotherapy and thermal phototherapy for tumors that over-express receptors of the gastrin releasing peptide; Sistema multifuncional de radioterapia y fototerapia termica para tumores que sobre-expresan receptores del peptido liberador de gastrina

    Energy Technology Data Exchange (ETDEWEB)

    Jimenez M, N. P.

    2014-07-01

    The aim of this research was to prepare and characterize a multifunctional system of {sup 177}Lu and {sup 99m}Tc-labelled gold nanoparticles conjugated to Tat(49 57)-Lys{sup 3} bombesin ({sup 177}Lu/{sup 99m}Tc- AuNP-Tat-Bn) and to evaluate the radiation absorbed dose in GRP receptor positive PC3 tumours induced in mice (human prostate cancer cells), as well as to evaluate the thermal effect produced by the multifunctional system in PC3 cancer cells. The preparation of the system involved the conjugation of Bn-Tat, DOTA-GGC and HYNICTOC peptides to AuNP of 20 nm or 5 nm in diameter. The radiolabeling of the system with {sup 99m}Tc was carried out through the ligand HYNIC-TOC and with the {sup 177}Lu through DOTA-GGC. The functionalization of peptides to AuNP, was accomplished through a spontaneous reaction of thiol groups. The system was characterized by spectroscopic techniques while radiochemical purity was determined by size-exclusion molecular chromatography and ultrafiltration. Various internalization trials and non-specific binding were tested to demonstrate the affinity of the system to PC3 cells. The thermal effect was evaluated incubating the system into PC3 cells and irradiating it with a Nd:YAG pulsed laser beam and monitoring the temperature; after irradiation, cell viability was measured. In the evaluation of absorbed dose in mice with induced tumours, the system was administered intratumorally and later, mice were sacrificed, relevant organs and tumor were extracted, activity was quantified and radiopharmaceutical models were obtained for each organ and tumor to be used in the accumulated activity and absorbed dose calculation by the MIRD methodology. Finally, to establish the system location at cellular level, fluorescent images of the system incubated in PC3 cells were acquired with an epi fluorescent microscope. Tem, UV-Vis, XP S and Far-IR spectroscopy techniques demonstrated that AuNPs were functionalized with peptides through interactions with

  2. Re-188 Enhances the Inhibitory Effect of Bevacizumab in Non-Small-Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Jie Xiao

    2016-09-01

    Full Text Available The malignant behaviors of solid tumors such as growth, infiltration and metastasis are mainly nourished by tumor neovascularization. Thus, anti-angiogenic therapy is key to controlling tumor progression. Bevacizumab, a humanized anti-vascular endothelial growth factor (VEGF antibody, plus chemotherapy or biological therapy can prolong survival for cancer patients, but treatment-related mortality is a concern. To improve inhibitory effect and decrease side-effects on non-small-cell lung cancer (NSCLC, we used Re-188, which is a β emitting radionuclide, directly labeled with bevacizumab for radioimmunotherapy in a human A549 tumor model. Cytotoxic assay data showed that, after 188ReO4− or 188Re-bevacizumab at different concentration for 4 and 24 h, a time- and radioactivity does-dependent reduction in cell viability occurred. Also, an apoptosis assay conformed great apoptosis in the 188Re-bevacizumab group compared with controls and other treatment groups. In vivo, tumor volumes in the 188Re-bevacizumab (11.1 MBq/mice group were not reduced but growth was delayed compared with other groups. Thus, 188Re-bevacizumab enhanced the therapeutic effect of bevacizumab, suggesting a potential therapeutic strategy for NSCLC treatment.

  3. Standardization of methodology to derivatization and radiolabeling of the anti-CD20 monoclonal antibody from bifunctional chelator DOTA-NHS-Ester

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana V.F.; Akanji, Akinkunmi G.; Santos, Josefina S.; Pujatti, Priscilla B.; Couto, Renata M.; Massicano, Felipe; Araujo, Elaine Bortoleti de [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)], E-mail: adriana.avfernandes@gmail.com

    2009-07-01

    Lymphomas are cancers of the lymphatic system, being the most common the non-Hodgkin lymphoma (NHL). The Radioimmunotherapy (RIT), that increase the cytotoxic effect of monoclonal antibodies (mAb), therefore labeling these Mab with different radioisotopes. RIT combines the specificity of the antibody and the toxicity of the radionuclides. The mAb anti-CD20 is used for treatment of relapse or refractory NHL. The labeling of anti- CD20 with {sup 177}Lu, requires a bifunctional chelating agent that is designed to make a 'connect bridge' between the mAb and the radionuclide. The incorporation of the chelating group in mAb structure is called derivatization. The aim of this work is to study the derivatization of anti-CD20 antibody with DOTA-NHS-ester chelating group and labeling parameters to produce {sup 177}Lu-DOTA-Anti CD20. Five milligrams of anti-CD20 were purified by dialysis against phosphate buffer pH 8.0 and derivatized with DOTA-NHS-ester in 1:250, 1:500 and 1:1000 molar ratios. The reaction was conducted for 1 hour in gently mixing at room temperature and remained under refrigeration for 48 hours. The reaction mixture was purified in gel column Sephadex G-50 ; the aliquots that presented greater protein concentration, were mixed and concentrated. The purified antibody conjugated was added to 111-185MBq (3-5mCi) of {sup 177}LuCl3 diluted in 0.4 M acetate buffer pH 5.5. Radiochemical purity was less than 95% in all the molar ratios, indicating necessity of the purification after the labeling. The mAb derivatized showed stable when stored for to 1 month to 4 deg C and 4 days at -20 deg C. (author)

  4. Lu-177-Labeled Zirconia Particles for Radiation Synovectomy.

    Science.gov (United States)

    Polyak, Andras; Nagy, Lívia Naszályi; Drotár, Eszter; Dabasi, Gabriella; Jóba, Róbert P; Pöstényi, Zita; Mikolajczak, Renata; Bóta, Attila; Balogh, Lajos

    2015-12-01

    The present article describes the preparation of β-emitter lutetium-177-labeled zirconia colloid and its preliminary physicochemical and biological evaluation of suitability for local radionuclide therapy. The new (177)Lu-labeled therapeutic radiopharmaceutical candidate was based on the synthesis mode of a previously described zirconia nanoparticle system. The size and shape of the developed radiopharmaceutical compound were observed through a scanning electron microscope and dynamic light scattering methods. The radiocolloid had a 1.7 μm mean diameter and showed high in vitro radiochemical and colloid size stability at room temperature and during the blood sera stability test. After the in vitro characterizations, the product was investigated in the course of the treatment of a spontaneously diseased dog veterinary patient's hock joint completed with single-photon emission computed tomography (SPECT) imaging follow-up measurements and a dual-isotope SPECT imaging tests with conventional (99m)Tc-methanediphosphonic acid bone scintigraphy. In the treated dog, no clinical side-effects or signs of histopathological changes of the joints were recorded during the treatment. SPECT follow-up studies clearly and conspicuously showed the localization of the (177)Lu-labeled colloid in the hock joint as well as detectable but negligible leakages of the radiocolloid in the nearest lymph node. On the basis of biological follow-up tests, the orthopedic team assumed that the (177)Lu-labeled zirconia colloid-based local radionuclide therapy resulted in a significant and long-term improvement in clinical signs of the patient without any remarkable side-effects.

  5. uPAR Targeted Radionuclide Therapy with 177Lu-DOTA-AE105 Inhibits Dissemination of Metastatic Prostate Cancer

    DEFF Research Database (Denmark)

    Persson, Morten; Juhl, Karina; Rasmussen, Palle

    2014-01-01

    value of 100 nM in a competitive binding experiment. In vivo, uPAR targeted radionuclide therapy significantly reduced the number of metastatic lesions in the disseminated metastatic prostate cancer model, when compared to vehicle and nontargeted 177Lu groups (p bioluminescence imaging...... with bioluminescence imaging in a cohort of animals during the treatment study. In conclusion, uPAR targeted radiotherapy resulted in a significant reduction in the number of metastatic lesions in a human metastatic prostate cancer model. Furthermore, we have provided the first evidence of the potential...

  6. Peptide receptor radionuclide therapy (PRRT): clinical significance of re-treatment?

    Energy Technology Data Exchange (ETDEWEB)

    Virgolini, Irene [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Collaboration: The Innsbruck Team

    2015-12-15

    PRRT appears to be the most effective therapeutic option in the management of inoperable or metastasized NET patients with limited side effects if dose limits are respected. In patients with relapse after a first treatment period with {sup 90}Y-DOTATOC, multiple re-treatment cycles with {sup 177}Lu-DOTATATE are feasible, safe and efficacious. Quantitative imaging by dosimetry adds to formulate personalized and evidence-based treatment protocols. However, despite the large body of evidence regarding efficacy and safety of PRRT, the absence of prospective randomized controlled trials questions the utility of PRRT in the community. Furthermore, the growing number of pharmacological or liver-directed therapeutic options competes with the confusion based on the variety of somatostatin analogues to determine the optimal choice and sequencing of PRRT in the individual patient. However, the efficacy of PRRT should not be questioned rather than it should be explored as to when PRRT might be optimally applied in the sequence of available therapy modalities. The results of the present study by the Italian group [5] emphasizes that radiopharmaceuticals are still underused. Despite the huge potential of PRRT the non-availability of PRRT in many countries still limits its widespread use. After acquiring the exclusive rights for {sup 177}Lu-DOTATATE with granted orphan designation, the company Advanced Accelerator Applications (AAA) is currently running a phase III study comparing treatment with {sup 177}Lu-DOTATATE to Octreotide LAR in patients with inoperable, progressive, somatostatin receptor-positive, midgut carcinoid tumours with the aim of registering the radiopharmaceutical under the commercial name of Lutathera. Together with orphan designation also to other somatostatin-based radiopharmaceuticals, such as {sup 90}Y-DOTATOC, {sup 177}Lu-DOTATOC and the {sup 68}Ga-labelled somatostatin antagonist OPS202, these developments promote the advancement of PRRT and PET imaging

  7. In vivo comparative study of hydroxyapatite labeled with different radioisotopes: evaluation of the scintigraphic images

    Energy Technology Data Exchange (ETDEWEB)

    Couto, Renata Martinussi; Barboza, Marycel Figols de; Souza, Adriano Aparecido de; Muramoto, Emiko; Mengatti, Jair; Araujo, Elaine Bortoleti de, E-mail: rmcouto@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Radiofarmacia

    2008-07-01

    Rheumatoid arthritis (RA) is a chronic inflammatory disorder of joints that is characterized by the inflammation and proliferation of synovial tissues. Approximately 3% of the adult population in the world is affected by this disease which causes pain, joint immobility and disability. Adyo synovectomy (RSV) is a radiotherapeutic modality where a b--emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy in the treatment of RA and other inflammatory arthropathies. There are several radionuclides available for this purpose such as {sup 177}Lu, {sup 90}Y, {sup 153}Sm, {sup 165}Dy, and {sup 166}Ho. Hydroxyapatite (HA) is one of the preferred particulates for this application because it is the major chemical constituent of skeletal bone and it is converted into Ca and PO4 ions in the body. In addition HA is completely eliminated over a period of six weeks. The aim of this work is to compare the in vivo stability of hydroxyapatite labeled with {sup 177}Lu, {sup 90}Y and {sup 153}Sm in order to determine the influence of the radionuclide on biological pattern. In biological studies, 100mL of labeled HAs suspended in normal saline were injected into normal knee joints of Wistar rats and the retention of the activity into the synovium was determined. Labeled particles were also injected by intravenous and intramuscular administration, to verify the biodistribution in the case of an eventual leakage of the products from the joint. Sequential scintigraphic images were acquired from 1 hour to 7 days p.i. after anesthetizing the animals with ketamine. Hydroxyapatite was radiolabeled by all radionuclides with high yield. {sup 177}Lu-HA, {sup 90}Y-HA and {sup 153}Sm-HA were retained in the joint for 7 days, showing

  8. Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

    DEFF Research Database (Denmark)

    Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf

    2015-01-01

    . Following 2, 24 or 48 h of inflammation we calculated permeability-surface area product (PS) for [(51)Cr]-EDTA in the trigeminal ganglion (TG), spinal trigeminal nucleus, cortex, periaqueductal grey and cerebellum. RESULTS: We observed that [(51)Cr]-EDTA did not pass into the central nervous system (CNS...

  9. Single-tracer technique to evaluate pulmonary edema and its application to detect the effect of hexamethylene diisocyanate trimer aerosol exposures

    Energy Technology Data Exchange (ETDEWEB)

    Valentini, J.E.; Wong, K.L.; Alarie, Y.

    1983-07-01

    Two hours after a four-hour exposure to hexamethylene diisocyanate trimer (HDIt) aerosol between 2.5 and 39 mg/m3, mice were injected iv with /sup 51/Cr-EDTA (chromium ethylenediaminetetraacetate). Ten minutes later the lung was lavaged. A larger amount of /sup 51/Cr-EDTA was detected in the lung lavage of HDIt mice than of controls in a concentration-related fashion. The concentration-response curve was shifted to the left compared with that constructed using lung weight increase as response. Kinetic studies of the plasma level of /sup 51/Cr-EDTA revealed a three-exponential profile in normal mice, and similar plasma levels were obtained with mice exposed to 18-24 mg/m3 HDIt. However, both the amount of /sup 51/Cr-EDTA in the alveolar space and concentration in the pulmonary extravascular compartment were higher in HDIt-exposed mice than in controls. The data of /sup 51/Cr-EDTA distribution in the lung were fitted with a three-compartment model. According to the model, HDIt exposures increase the permeability constants of /sup 51/Cr-EDTA transport into the alveolar space from blood which accounts for the larger amount of /sup 51/Cr-EDTA in lung lavage of HDIt-exposed mice. This /sup 51/Cr-EDTA injection and lung lavage technique is a sensitive method for detecting pulmonary edema.

  10. Immune functions in beluga whales (Delphinapterus leucas): Evaluation of natural killer cell activity.

    NARCIS (Netherlands)

    S. De Guise (Sylvain); P.S. Ross (Peter); A.D.M.E. Osterhaus (Albert); D. Martineau (Daniel); P. Beland; M. Fournier (Michel)

    1997-01-01

    textabstractNatural killer (NK) activity, an important non-specific defense mechanism against viral infections and tumors, was demonstrated in beluga whales using two different methods: 51Cr release and flow cytometry. Using the 51Cr release assay, NK activity in belugas was shown to be higher again

  11. Influence of renal function on the elimination of morphine and morphine glucuronides

    DEFF Research Database (Denmark)

    Wolff, Jesper; Bigler, Dennis Richard; Christensen, C B

    1988-01-01

    plasma. No significant correlation was found between total body clearance of unconjugated morphine and 51Cr-EDTA clearance. However, patients with renal insufficiency had impaired elimination of morphine glucuronides, and the apparent clearance was significantly correlated with the 51Cr-EDTA clearance (r...

  12. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik

    1996-01-01

    -acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p ...Tc-MBP equal the clearances of 51Cr-EDTA is correct from a clinical point of view. We found that the uptake of the tracers in soft tissue and the renal handling of 51Cr-EDTA and 99mTc-MBP are also similar. The differences between the clearance values for 51Cr-EDTA and 99mTc-MBP may be explained...

  13. Patient-specific dosimetry in peptide receptor radionuclide therapy: a clinical review.

    Science.gov (United States)

    Chalkia, M T; Stefanoyiannis, A P; Chatziioannou, S N; Round, W H; Efstathopoulos, E P; Nikiforidis, G C

    2015-03-01

    Neuroendocrine tumours (NETs) belong to a relatively rare class of neoplasms. Nonetheless, their prevalence has increased significantly during the last decades. Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment approach for inoperable or metastasised NETs. The therapeutic effect is based on the binding of radiolabelled somatostatin analogue peptides with NETs' somatostatin receptors, resulting in internal irradiation of tumours. Pre-therapeutic patient-specific dosimetry is essential to ensure that a treatment course has high levels of safety and efficacy. This paper reviews the methods applied for PRRT dosimetry, as well as the dosimetric results presented in the literature. Focus is given on data concerning the therapeutic somatostatin analogue radiopeptides (111)In-[DTPA(0),D-Phe(1)]-octreotide ((111)In-DTPA-octreotide), (90)Y-[DOTA(0),Tyr(3)]-octreotide ((90)Y-DOTATOC) and (177)Lu-[DOTA(0),Tyr(3),Thr(8)]-octreotide ((177)Lu-DOTATATE). Following the Medical Internal Radiation Dose (MIRD) Committee formalism, dosimetric analysis demonstrates large interpatient variability in tumour and organ uptake, with kidneys and bone marrow being the critical organs. The results are dependent on the image acquisition and processing protocol, as well as the dosimetric imaging radiopharmaceutical.

  14. {sup 213}Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

    Energy Technology Data Exchange (ETDEWEB)

    Kratochwil, C.; Giesel, F.L.; Mier, W.; Haberkorn, U. [University Hospital Heidelberg, Department of Nuclear Medicine, Heidelberg (Germany); Bruchertseifer, F.; Apostolidis, C.; Morgenstern, A. [European Commission, Institute for Transuranium Elements, Karlsruhe (Germany); Boll, R.; Murphy, K. [Oak Ridge National Laboratory, Oak Ridge, TN (United States)

    2014-11-15

    Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as {sup 90}Y/{sup 177}Lu-DOTATOC is a new therapeutic option in neuroendocrine cancer. Alternative treatments for patients with refractory disease are rare. Here we report the first-in-human experience with {sup 213}Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with {sup 90}Y/{sup 177}Lu-DOTATOC were treated with an intraarterial infusion of {sup 213}Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of {sup 213}Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and {sup 68}Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of {sup 213}Bi-DOTATOC was evaluable with 440 keV gamma emission scans, and demonstrated specific tumour binding. Enduring responses were observed in all treated patients. Chronic kidney toxicity was moderate. Acute haematotoxicity was even less pronounced than with the preceding beta therapies. TAT can induce remission of tumours refractory to beta radiation with favourable acute and mid-term toxicity at therapeutic effective doses. (orig.)

  15. Lutetium 177-DOTA-TATE therapy for esthesioneuroblastoma: A case report

    Science.gov (United States)

    Sabongi, Juliano Guerra; Gonçalves, Mônica Carboni Pereira; Alves, Cira Danielle Casado; Alves, João; Scapulatempo-Neto, Cristovam; Moriguchi, Sonia Marta

    2016-01-01

    Esthesioneuroblastoma (ENB), also known as olfactory neuroblastoma, is a rare malignant tumor that accounts for 3% of all tumors of the nasal cavity. The incidence of ENB is 0.4 cases per million in the general population, and the most common symptoms are nasal obstruction and epistaxis. Previous studies have indicated the presence of somatostatin receptors in this tumor type. Common treatment strategies for ENB include resection and adjuvant radiotherapy and/or chemotherapy (combined treatment); however, the rate of recurrence is high. Treatment of neuroendocrine tumors using radionuclides bound to somatostatin analogues is well established in clinical practice. However, a standard and effective therapeutic approach has not been reported for ENB. The current study described the case of a 74-year-old female with numerous recurrences of ENB following multiple treatments and without possibility of resection. The patient was treated with the radiolabeled-somatostatin analogue, 177Lutetium-DOTA-octreotate (177Lu-DOTA-TATE), which successfully controlled the disease. This suggests that 177Lu-DOTA-TATE is a potential treatment for ENB and may represent an effective alternative and novel therapeutic strategy for this disease. PMID:27882120

  16. Current status and future perspectives of PSMA-targeted therapy in Europe: opportunity knocks

    Energy Technology Data Exchange (ETDEWEB)

    Pfestroff, A.; Luster, M. [University Hospital Marburg, Department of Nuclear Medicine, Marburg (Germany); Jilg, C.A. [University Hospital Freiburg, Department of Urology, Freiburg (Germany); Olbert, P.J. [University Hospital Marburg, Department of Urology, Marburg (Germany); Ohlmann, C.H. [Saarland University Hospital, Department of Urology, Homburg/Saar (Germany); Lassmann, M. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Maecke, H.R. [University Hospital Freiburg, Department of Nuclear Medicine and Radiopharmacy, Freiburg (Germany); Ezziddin, S. [Saarland University Hospital, Department of Nuclear Medicine, Homburg/Saar (Germany); Bodei, L. [European Institute of Oncology, Department of Nuclear Medicine, Milan (Italy); Collaboration: on behalf of the Radionuclide Therapy Committee of the European Association of Nuclear Medicine

    2015-12-15

    {sup 177}Lu-based PSMA-targeted therapy appears to be a promising treatment for advanced PCA. However, lessons should be learned from PRRT of neuroendocrine tumours, which was referred to as a ''promising'' tool for 15 years before the advent of evidence-based comparative studies. This experience strongly suggests that the communities involved with PSMA-targeted therapy, namely nuclear medicine, urology, radiochemistry, and medical physics, should capitalize without delay on the great opportunity to conduct well-designed prospective studies. Doing so should advance this modality from the proof-of principle stage to the potential standard-of-Care-stage. From our perspective, crucial components of this process are: - Harmonization of therapy protocols - Implementation of a patient selection algorithm into clinical routine - Standardization of toxicity assessment - Establishment of standardized dosimetry protocols to assess safety and efficacy - Transfer of expertise in PSMA therapy throughout Europe - Regulatory approval of {sup 177}Lu-PSMA-targeted compounds.

  17. Labelling of the peptide Dota-Octreotate with Lutetium 177; Marcado del peptido Dota-Octreotate con Lutecio 177

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez B, C.A

    2004-07-01

    In this work is described the optimization of the reaction conditions to obtain the complex {sup 177} Lu-Dota-TATE with a radiochemical purity > 95%, even so the studies of stability In vitro to the dilution in saline solution, stability in human serum and challenge to the cystein. The biodistribution studies are presented in mice Balb-C and the tests of biological recognition using one lines cellular of pancreatic adenoma (AR42-J). The obtained results show a high stability of the radio complex in vitro, since it doesn't suffer trans chelation from the Lutetium-177 to plasmatic proteins. The biodistribution tests in mice Balb-C demonstrated an appropriate lipophilly of the complex to be excreted in more proportion by the kidneys without significant accumulation in healthy tissues. It is necessary to mention that the drop activity specifies (3.54 {mu}g / 37 MBq) obtained in the irradiation of {sup 176} Lu{sub 2}O{sub 3} it allowed to verify the union of the {sup 177}Lu-Dota-Tate to membrane receivers but without being able to obtain the saturation curves and competition required to characterize quantitatively the biological recognition. (Author)

  18. Synthesis of gels with basis of titanium tungstates as matrixes of radioactive generators; Sintesis de geles a base de titanio tungstenatos como matrices de generadores radiactivos

    Energy Technology Data Exchange (ETDEWEB)

    Galico C, L

    2005-07-01

    The heteropolyanions, compounds formed by the union of molybdates or tungstates polyanions with atoms of metals like zirconium, titanium, cerium, thorium, tin, etc., have been used as generator matrixes of {sup 99m} Tc or {sup 188} Re. Particularly they have been studied and produced successfully in our laboratory, generators of {sup 99} Mo/ {sup 99}m Tc at basis of gels zirconium molybdates and titanium molybdates. Considering that the molybdenum and tungsten, as well as the technetium and the rhenium, its belong to the same groups of transition metals, it is feasible that gels can be synthesized at basis of titanium tungstates, continuing a methodology similar to that of the gels titanium molybdates or zirconium molybdates, to produce generators {sup 188} W/ {sup 188} Re. The {sup 188} Re possess nuclear characteristics that make it attractive for therapeutic applications, since, it emits {beta}{sup -} particles of a great energy (2.12 MeV); joined to the possibility of being able to unite to different ligands (bifunctional agents) and biomolecules (antibodies or fragments of proteins), as it makes the {sup 99m} Tc, useful in radioimmunotherapy. Commercially the {sup 188} Re generators use a chromatographic column loaded with alumina where the {sup 188} Re, it is adsorbed and eluted the {sup 188} ReO{sub 4}{sup -} by means of a saline solution The alumina adsorbs around 0.2% of the {sup 188} Re, situation that forces to use {sup 188} Re of a high specific activity. The use of the gels technology, allows to work with medium or low specific activities of {sup 188} Re, opening the possibility of their production in countries whose nuclear capacity is medium or low. In particular, the synthesized gels with basis of titanium offer the possibility of being synthesized with non active material, for later on to be irradiated and directly produce the generator, since, the titanium {sup 51} Ti, unique radioisotope produced by the titanium, has a half life of 5.79 min. This

  19. Self-assembled monolayers on gold for the fabrication of radioactive stents

    NARCIS (Netherlands)

    Bommel, van Kjeld J.C.; Friggeri, Arianna; Mateman, Dorine; Geurts, Frank A.J.; Leerdam, Kees G.C.; Verboom, Willem; Veggel, van Frank C.J.M.; Reinhoudt, David N.

    2001-01-01

    An innovative and easily applicable method for the fabrication of radioactive stents, to be used for the treatment of restenosis, is presented. By incorporating the b-emitting radioisotopes 186Re, 188Re, 90Y, or 32P into sulfur-containing adsorbates, it becomes possible to cover a gold surface with

  20. 188Re直接法标记CD45单抗及其体内生物分布研究%Direct-radiolabeling of CD45 monoclonal antibody with rhenium-188 and its biodistribution in normal mice

    Institute of Scientific and Technical Information of China (English)

    郑文莉; 李贵平; 黄宝丹; 杜丽; 黄凯

    2013-01-01

    Objective With direct-labeling method of CD45 McAb with 188Re, to investigate its bio-distribution character in normal mice. Methods The disulfide bond in the molecule of CD45 monoclonal antibody was reduced to form a mercapto group by the mercaptoethanol (2-ME). The labeling was conducted by stannous chloride used as reductant of 188Re, and sodium glucoheptonate as intermediate.weak ligands, then 188Re was directly labeled CD45 mAb alone; The reaction mixture was separated and purified throuth the PD-10 column;Labeling efficiency and radiochemical purity were measured by the paper chromatography. Then stability of 188Re labeled CD45 McAb was determined in vitro. The biodistribution in the healthy Kunming mice after intravenous injection of 188Re-CD45 McAb was determined. Results The labeling efficiency of 188Re-CD45 McAb was (85.25±2.63)%, and radiochemical purity was (92.54±3.56)%. The specific activity was (2.06±0.07) TBq/mmol;The radiochemical purity of 188Re-CD45 McAb was (64.33±1.53)% after incubating 24 h in room temperature. While mixed the saline and healthy rat serum at 37℃for 24 h, the radiochemical purity was (64. 2±3. 77)%and(56. 7±4. 16)%, respectively. The biodistribution result showed that the radioactivity in body was mainly distributed in kidney and liver, followed by lung, bone and blood. Conclusion The method of direct-labeling CD45 McAb with 188Re is not only simple, but also has high labeling efficiency. 188Re-CD45 McAb has good stability in vitro. After injected intravenously, radioactive label is mainly excreted through kidneys with a higher accumulation in liver, and it accords with the in vivo kinetics characteristic of labeled antibody.%目的:利用188Re直接法标记CD45单抗,探讨其在正常小鼠体内的生物学分布特性。方法应用2-巯基乙醇(2-ME)还原CD45单抗分子中的二硫键形成巯基;以氯化亚锡作为188Re的还原剂,葡庚糖酸钠为中间弱配体,188Re直接标记CD45

  1. Glomerular filtration rate estimated from the uptake phase of 99mTc-DTPA renography in chronic renal failure

    DEFF Research Database (Denmark)

    Petersen, L J; Petersen, J R; Talleruphuus, U

    1999-01-01

    The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea.......The purpose of the study was to compare the estimation of glomerular filtration rate (GFR) from 99mTc-DTPA renography with that estimated from the renal clearance of 51Cr-EDTA, creatinine and urea....

  2. Immune functions in beluga whales (Delphinapterus leucas): Evaluation of natural killer cell activity.

    OpenAIRE

    Guise, Sylvain De; Ross, Peter; Osterhaus, Albert; Martineau, Daniel; Beland, P; Fournier, Michel

    1997-01-01

    textabstractNatural killer (NK) activity, an important non-specific defense mechanism against viral infections and tumors, was demonstrated in beluga whales using two different methods: 51Cr release and flow cytometry. Using the 51Cr release assay, NK activity in belugas was shown to be higher against K-562 than against YAC-1 cell lines. Moreover, it was enhanced by the addition of human recombinant interleukin-2 with both cell lines. NK activity evaluated by flow cytometry in the peripheral ...

  3. Comprehensive evaluation of a somatostatin-based radiolabelled antagonist for diagnostic imaging and radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xuejuan; Fani, Melpomeni [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); Schulz, Stefan [Jena University Hospital - Friedrich Schiller University Jena, Department of Pharmacology and Toxicology, Jena (Germany); Rivier, Jean [The Salk Institute for Biological Studies, The Clayton Foundation Laboratories for Peptide Biology, La Jolla, CA (United States); Reubi, Jean Claude [University of Bern, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, Bern (Switzerland); Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Basel (Switzerland); University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-12-15

    Targeting of tumours positive for somatostatin receptors (sst) with radiolabelled peptides is of interest for tumour localization, staging, therapy follow-up and targeted radionuclide therapy. The peptides used clinically are exclusively agonists, but recently we have shown that the radiolabelled somatostatin-based antagonist {sup 111}In-DOTA-sst2-ANT may be preferable to agonists. However, a comprehensive study of this radiolabelled antagonist to determine its significance was lacking. The present report describes the evaluation of this novel antagonist labelled with {sup 111}In and {sup 177}Lu in three different tumour models. Radiopeptide binding, internalization and dissociation studies were performed using cells expressing HEK293-rsst{sub 2}. Biodistribution studies were performed in HEK293-rsst{sub 2}, HEK293-hsst{sub 2} and HEK293-rsst{sub 3} xenografted mice. Saturation binding analysis confirmed earlier IC{sub 50} data for {sup 111/nat}In-DOTA-sst2-ANT and showed similar affinity of {sup 177/nat}Lu-DOTA-sst2-ANT for the sst{sub 2}. Only low internalization was found in cell culture (6.68 {+-} 0.06 % at 4 h), which was not unexpected for an antagonist, and this could be further reduced by the addition of sucrose. No internalization was observed in HEK293 cells not expressing sst. Both results indicate that the internalization was specific. {sup 111}In-DOTA-sst2-ANT and {sup 177}Lu-DOTA-sst2-ANT were shown to target tumour xenografts expressing the rat and the human sst{sub 2} receptor with no differences in their uptake or pharmacokinetics. The uptake in rsst{sub 2} and hsst{sub 2} was high (about 30 %IA/g 4 h after injection) and surprisingly long-lasting (about 20-23 %IA/g 24 h after injection). Kidney uptake was blocked by approximately 50 % by lysine or Gelofusine. These results indicate that radiolabelled somatostatin-based antagonists may be superior to corresponding agonists. The long tumour retention time of {sup 177}Lu-DOTA-sst2-ANT indicates that

  4. What a difference a carbon makes: H₄octapa vs H₄C3octapa, ligands for In-111 and Lu-177 radiochemistry.

    Science.gov (United States)

    Price, Eric W; Zeglis, Brian M; Cawthray, Jacqueline F; Lewis, Jason S; Adam, Michael J; Orvig, Chris

    2014-10-06

    The acyclic ligands H4C3octapa and p-SCN-Bn-H4C3octapa were synthesized for the first time, using nosyl protection chemistry. These new ligands were compared to the previously studied ligands H4octapa and p-SCN-Bn-H4octapa to determine the extent to which the addition of a single carbon atom to the backbone of the ligand would affect metal coordination, complex stability, and, ultimately, utility for in vivo radiopharmaceutical applications. Although only a single carbon atom was added to H4C3octapa and the metal donor atoms and denticity were not changed, the solution chemistry and radiochemistry properties were drastically altered, highlighting the importance of careful ligand design and radiometal-ligand matching. It was found that [In(C3octapa)](-) and [Lu(C3octapa)](-) were substantially different from the analogous H4octapa complexes, exhibiting fluxional isomerization and a higher number of isomers, as observed by (1)H NMR, VT-NMR, and 2D COSY/HSQC-NMR experiments. Past evaluation of the DFT structures of [In(octapa)](-) and [Lu(octapa)](-) revealed very symmetric complexes; in contrast, the [In(C3octapa)](-) and [Lu(C3octapa)](-) complexes were much less symmetric, suggesting lower symmetry and less rigidity than that of the analogous H4octapa complexes. Potentiometric titrations revealed the formation constants (log K(ML), pM) were ~2 units lower for the In(3+) and Lu(3+) complexes of H4C3octapa when compared to that of the more favorable H4octapa ligand (~2 orders of magnitude less thermodynamically stable). The bifunctional ligands p-SCN-Bn-H4C3octapa and p-SCN-Bn-H4octapa were conjugated to the antibody trastuzumab and radiolabeled with (111)In and (177)Lu. Over a 5 day stability challenge experiment in blood serum, (111)In-octapa- and (111)In-C3octapa-trastuzumab immunoconjugates were determined to be ~91 and ~24% stable, respectively, and (177)Lu-octapa- and (177)Lu-C3octapa-trastuzumab, ~89% and ~4% stable, respectively. This work suggests that 5

  5. New measurements of excitation functions of 186W(p,x) nuclear reactions up to 65 MeV. Production of a 178W/178mTa generator

    Science.gov (United States)

    Tárkányi, F.; Ditrói, F.; Takács, S.; Hermanne, A.

    2017-01-01

    New experimental excitation functions for proton induced reactions on natW are presented in the 32-65 MeV energy range. The cross-sections for natW(p,xn)186,184m,184g,183, 182m,182g,181Re, natW(p,x)178W, natW(p,x)183,182, 180m, 177,176,175Ta, 175Hf and 177Lu were measured via an activation method by using a stacked-foil irradiation technique and high resolution gamma-ray spectroscopy. The results were compared with predicted values obtained with the nuclear reaction code TALYS (results taken from the TENDL 2014 and TENDL 2015 on-line libraries). Production routes of the medically relevant radionuclides 186Re, the 178W → 178Ta generator and 181W are discussed.

  6. Treatment of neuroendocrine tumours with radioactive labelled somatostatin analogues; Therapie neuroendokriner Tumoren mit radioaktiv markierten Somatostatinanaloga

    Energy Technology Data Exchange (ETDEWEB)

    Geisler, J.; Bartenstein, P.; Haug, Alexander R. [Ludwig-Maximilians-Univ., Muenchen (Germany). Klinik fuer Nuklearmedizin

    2011-12-15

    Therapy of neuroendocrine tumors (NET) using radiolabelled somatostatin receptors such as {sup 177}-Lu-DOTATATE or {sup 90}Y-DOTATOC is gaining more and more importance. Due to the over expression of somatostatin receptors in NET the tumor-to-background ratio is very favourable. A significant therapy response is achievable between 20% and up to 46% of treated patients with a median time to progression of up to 40 months. Furthermore, this kind of therapy is very beneficial in the case of hormonal active, functional NET in terms of symptom control. Also quality of life is significantly improved after therapy, even in non-responding patients. The most common side effects of this therapy are nausea, vomiting and transient hematologic toxicity. However, late serious side effects such as renal impairment or myelodysplastic syndrome are rare if renal protection is used during the course of therapy. (orig.)

  7. Standardization of (166m)Ho and 243Am/239Np by live-timed anti-coincidence counting with extending dead time.

    Science.gov (United States)

    da Silva, C J; Loureiro, J S; Delgado, J U; Poledna, R; Moreira, D S; Iwahara, A; Tauhata, L; da Silva, R L; Lopes, R T

    2012-09-01

    The National Laboratory for Metrology of Ionizing Radiation (LNMRI)/Brazil acquired (166m)Ho and (243)Am/(239)Np solutions from commercial suppliers in order to realize primary standardization and therefore reducing the associated uncertainties. The method used in the standardization was the live-timed 4πβ(LS)-γ(ΝaI(Tl)) anticoincidence counting. The live-timed anticoincidence system is operated since 2006 in LNMRI and is composed of two MTR2 modules donated by Laboratoire National Henri Becquerel (LNE-LNHB)/France. The data acquisition system uses a homemade LabView program and an Excel file for calculus. These systems have been used for primary standardization at LNMRI for many radionuclides and recently took part in the (124)Sb and (177)Lu International Key Comparisons with good performance.

  8. Source self-attenuation in ionization chamber measurements of (57)Co solutions.

    Science.gov (United States)

    Cessna, Jeffrey T; Golas, Daniel B; Bergeron, Denis E

    2016-03-01

    Source self-attenuation for solutions of (57)Co of varying density and carrier concentration was measured in nine re-entrant ionization chambers maintained at NIST. The magnitude of the attenuation must be investigated to determine whether a correction is necessary in the determination of the activity of a source that differs in composition from the source used to calibrate the ionization chamber. At our institute, corrections are currently made in the measurement of (144)Ce, (109)Cd, (67)Ga, (195)Au, (166)Ho, (177)Lu, and (153)Sm. This work presents the methods used as recently applied to (57)Co. A range of corrections up to 1% were calculated for dilute to concentrated HCl at routinely used carrier concentrations.

  9. Peptide receptor radionuclide therapy with lutetium-177 DOTATATE in a case of recurrent extradrenal retroperitoneal malignant paraganglioma with nodal and bone metastasis

    Directory of Open Access Journals (Sweden)

    Koramadai Karuppusamy Kamaleshwaran

    2015-01-01

    Full Text Available Extra-adrenal retroperitoneal paragangliomas (PGLs are rare tumors causing considerable difficulty in both, diagnosis and treatment. They can be unicentric or multicentric, tend to be locally invasive and therefore have a high incidence of local recurrence. PGLs shows somatostatin receptor positivity, which can be imaged with technetium-99m (Tc-99m-hydrazinonicotinyl-Tyr3-octreotide (HYNIC-TOC and can be treated with lutetium-177 (Lu-177 DOTATATE. We present a case of recurrent unresectable retroperitoneal PGL with nodal and bone metastases in a 27-year-old male, 6 months postsurgery detected with Tc-99m-HYNIC-TOC and was administered with peptide receptor radionuclide therapy using Lu-177 DOTATATE.

  10. Effect of a spacer moiety on radiometal labelled Neurotensin derivatives

    Energy Technology Data Exchange (ETDEWEB)

    Mascarin, A.; Valverde, I.E.; Mindt, T.L. [Univ. of Basel Hospital (Switzerland). Div. of Radiopharmaceutical Chemistry

    2013-07-01

    The binding sequence of the regulatory peptide Neurotensin, NT(8-13), represents a promising tumour-specific vector for the development of radiopeptides useful in nuclear oncology for the diagnosis (imaging) and therapy of cancer. A number of radiometal-labelled NT(8-13) derivatives have been reported, however, the effect of the spacer which connects the vector with the radiometal complex has yet not been investigated systematically. Because a spacer moiety can influence potentially important biological characteristics of radiopeptides, we synthesized three [DOTA({sup 177}Lu)]-X-NT(8-13) derivatives and evaluated the effect of a spacer (X) on the physico-chemical properties of the conjugate including lipophilicity, stability, and in vitro receptor affinity and cell internalization. (orig.)

  11. 68Ga-DOTA-NOC PET and peptide receptor radionuclide therapy in management of bilateral ovarian metastases from gastrointestinal carcinoid.

    Science.gov (United States)

    Singla, Suhas; Gupta, Santosh; Reddy, Rama Mohan; Durgapal, Prashant; Bal, C S

    2012-12-01

    The management of neuroendocrine tumours is challenging when curative surgery is ruled out because of distant metastases. We report a case of gastrointestinal carcinoid with bilateral ovarian metastases in a 50-year-old female who received octreotide therapy followed by peptide receptor radionuclide therapy and surgery thereafter. Somatostatin receptor expression on neuroendocrine tumours has implications in diagnosis and therapy. (68)Ga-DOTA-NOC PET is a recent advancement in the field of somatostatin receptor imaging. The lesions which demonstrate tracer uptake on positron emission tomographic studies can be further planned for treatment with octreotide and (177)Lu-DOTA-TATE. The case in discussion responded well to non-invasive treatment options before proceeding to definitive surgical management.

  12. Approximation of Sums of Experimental Radiative Strength Functions of Dipole Gamma-Transitions in the Region $E_\\gamma \\approx B_n$ for the Atomic Masses $40 \\leq a \\leq 200$

    CERN Document Server

    Sukhovoj, A M; Khitrov, V A

    2008-01-01

    The sums k(E1)+k(M1) of radiative strength functions of dipole primary gamma-transitions were approximated with high precision in the energy region of $0.5 < E_1 < B_n-0.5$ MeV for nuclei: 40K, 60Co, 71,74Ge, 80Br, 114Cd, 118Sn, 124,125Te, 128I, 137,138,139Ba, 140La, 150Sm, 156,158Gd, 160Tb, 163,164,165Dy, 166Ho, 168Er, 170Tm, 174Yb, 176,177Lu, 181Hf, 182Ta, 183,184,185,187W, 188,190,191,193Os, 192Ir, 196Pt, 198Au, 200Hg by sum of two independent functions. It has been shown that this parameter of gamma-decay are determined by the structure of the decaying and excited levels, at least, up to the neutron binding energy.

  13. Semiphenomenological approximation of the sums of experimental radiative strength functions for dipole gamma transitions of energy E γ below the neutron binding energy B n for mass numbers in the range 40 ≤ A ≤ 200

    Science.gov (United States)

    Sukhovoj, A. M.; Furman, W. I.; Khitrov, V. A.

    2008-06-01

    The sums of radiative strength functions for primary dipole gamma transitions, k( E1) + k( M1), are approximated to a high precision by a superposition of two functional dependences in the energy range 0.5 125Te, 128I, 137,138,139Ba, 140La, 150Sm, 156,158Gd, 160Tb, 163,164,165Dy, 166Ho, 168Er, 170Tm, 174Yb, 176,177Lu, 181Hf, 182Ta, 183,184,185,187W, 188,190,191,193Os, 192Ir, 196Pt, 198Au, and 200Hg nuclei. It is shown that, in any nuclei, radiative strength functions are a dynamical quantity and that the values of k( E1) + k( M1) for specific energies of gamma transitions and specific nuclei are determined by the structure of decaying and excited levels, at least up to the neutron binding energy B n .

  14. Use of radioactive substances in diagnosis and treatment of neuroendocrine tumors

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Knigge, Ulrich

    2015-01-01

    -DOTATATE, (68)Ga-DOTATOC and (68)Ga-DOTANOC are the three most often used PET tracers. They perform better than SPECT tracers and should be preferred. FDG-PET is well suited for visualization of most of the somatostatin receptor-negative tumors prognostic in NET patients. Also (11)C-5-HTP, (18)F-DOPA and (123)I...... of up to 3 years. Grade 3-4 kidney or bone marrow toxicity is seen in 1.5% and 9.5%, respectively, but are completely or partly reversible in most patients. (177)Lu-DOTATATE seems to have less toxicity than (90)Y-DOTATOC. However, until now only retrospective, non-randomized studies have been performed...

  15. Complete Remission of Metastatic Neuroendocrine Paragastric Carcinoma After "Neoadjuvant" Peptide Receptor Radionuclide Therapy and Surgery.

    Science.gov (United States)

    Schmidt, Matthias C; Uhrhan, Klara; Fischer, Thomas; Schmitz, Stephan; Markiefka, Birgid; Drzezga, Alexander; Stippel, Dirk

    2015-08-01

    A 48-year-old man presenting with upper abdominal pain was diagnosed with neuroendocrine tumor after biopsy of a paragastric mass with multiple liver metastases. (68)Ga-DOTATATE PET/CT showed intense uptake in the paragastric tumor and in multiple liver metastases not allowing primary surgery. Two cycles with cumulative 14.6 GBq (177)Lu-DOTATATE were given resulting in a considerable improvement. Subsequent surgery resulted in a complete remission as demonstrated by (68)Ga-DOTATATE PET/CT. Usually, peptide receptor radionuclide (PRRT) therapy is considered a palliative treatment. Few patients demonstrate a very favorable response allowing resection of the primary tumor after downstaging metastatic disease burden.

  16. In Vivo Monitoring of the Antiangiogenic Effect of Neurotensin Receptor-Mediated Radiotherapy by Small-Animal Positron Emission Tomography: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Simone Maschauer

    2014-04-01

    Full Text Available The neurotensin receptor (NTS1 has emerged as an interesting target for molecular imaging and radiotherapy of NTS-positive tumors due to the overexpression in a range of tumors. The aim of this study was to develop a 177Lu-labeled NTS1 radioligand, its application for radiotherapy in a preclinical model and the imaging of therapy success by small-animal positron emission tomography (µPET using [68Ga]DOTA-RGD as a specific tracer for imaging angiogenesis. The 177Lu-labeled peptide was subjected to studies on HT29-tumor-bearing nude mice in vivo, defining four groups of animals (single dose, two fractionated doses, four fractionated doses and sham-treated animals. Body weight and tumor diameters were determined three times per week. Up to day 28 after treatment, µPET studies were performed with [68Ga]DOTA-RGD. At days 7–10 after treatment with four fractionated doses of 11–14 MBq (each at days 0, 3, 6 and 10, the tumor growth was slightly decreased in comparison with untreated animals. Using a single high dose of 51 MBq, a significantly decreased tumor diameter of about 50% was observed with the beginning of treatment. Our preliminary PET imaging data suggested decreased tumor uptake values of [68Ga]DOTA-RGD in treated animals compared to controls at day 7 after treatment. This pilot study suggests that early PET imaging with [68Ga]DOTA-RGD in radiotherapy studies to monitor integrin expression could be a promising tool to predict therapy success in vivo. Further successive PET experiments are needed to confirm the significance and predictive value of RGD-PET for NTS-mediated radiotherapy.

  17. Lutetium-177 Labeled Peptides: The European Institute of Oncology Experience.

    Science.gov (United States)

    Carollo, Angela; Papi, Stefano; Chinol, Marco

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogues has shown encouraging results in various somatostatin receptor positive tumors. Partial remission rates up to 30% have been documented as well as significant improvements in quality of life and survival. This treatment takes advantage of the high specific binding of the radiolabeled peptide to somatostatin receptors overexpressed by the tumors thus being more effective on the tumor cells with less systemic side-effects. The development of macrocyclic chelators conjugated to peptides made possible the stable binding with various radionuclides. In particular 177Lu features favourable physical characteristics with a half-life of 6.7 days, emission of β- with energy of 0.5 MeV for treatment and γ-emissions suitable for imaging. The present contribution describes the learning process achieved at the European Institute of Oncology (IEO) since the first application of 90Y labeled peptides to the therapy of neuroendocrine tumors back in 1997. Continuous improvements led to the preparation of a safe 177Lu labeled peptide for human use. Our learning curve began with the identification of the optimal characteristics of the isotope paying attention to its chemical purity and specific activity along with the optimization of the parameters involved in the radiolabeling procedure. Also the radiation protection issues have been improved along the years and recently more and more attention has been devoted to the pharmaceutical aspects involved in the preparation. The overall issue of the quality has now been completed by drafting an extensive documentation with the goal to deliver a safe and reliable product to our patients.

  18. Kinetic and allometric models for dosimetry using radiopharmaceuticals labeled with lanthanides; Proposicao de modelos cineticos e alometricos para a dosimetria de radiofarmacos marcados com lantanideos

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Marina Ferreira

    2012-07-01

    This work proposes two models based in compartmental analyses: Animal model and Human model, using images from gamma camera measurements to determinate the kinetic constants of the {sup 177}Lu-DOTATATE to three animal species (rat Wistar, Armenian hamster and Syrian hamster) and to the human in biodistribution studies split in two phases: Phase 1 governed by uptake from the blood and Phase 2 governed by the real excretion. The kinetic constants obtained from the animals' data ere used to build allometric scaling to predict radiopharmaceutical biodistribution in the human employing relations by mass, metabolism, by life span and by physiological parameters. These extrapolation results were compared with the PRRT (Peptide receptor radiotherapy) patients kinetic data calculated using the Human model. The kinetic constants obtained from humans were used in dose assessment to PRRT patients considering MIRD 26 organs and tissues. Dosimetry results were in agreement with available results from literature. For the Phase 1 allometric scaling from kinetic data from the blood to the organs straight responsible for the {sup 177}Lu-DOTATATE metabolism and excretion - liver, kidneys and urinary bladder -show good correlation in the scaling by mass, metabolism and physiological and parameters. For the Phase 2, only the kinetic data from blood to the liver and to the kidneys show good correlation. Based in the anaesthetics inhibitory action over the renal excretion, there is not empirical basis to allow measurement times over 40 minutes in in vivo studies with small animals. Consequently, the Phase 1 results seem enough to make allometric scaling to assessment dose in PRRT. (author)

  19. Quantification of β-Cell Mass in Intramuscular Islet Grafts Using Radiolabeled Exendin-4

    Science.gov (United States)

    Espes, Daniel; Selvaraju, Ramkumar; Velikyan, Irina; Krajcovic, Martin; Carlsson, Per-Ola; Eriksson, Olof

    2016-01-01

    Background There is an increasing interest in alternative implantation sites to the liver for islet transplantation. Intramuscular implantation has even been tested clinically. Possibilities to monitor β-cell mass would be of huge importance not only for the understanding of islet engraftment but also for the decision of changing the immunosuppressive regime. We have therefore evaluated the feasibility of quantifying intramuscular β-cell mass using the radiolabeled glucagon like peptide-1 receptor agonist DO3A-VS-Cys40-Exendin-4. Methods One hundred to 400 islets were transplanted to the abdominal muscle of nondiabetic mice. After 3 to 4 weeks, 0.2 to 0.5 MBq [177Lu]DO3A-VS-Cys40-Exendin-4 was administered intravenously. Sixty minutes postinjection abdominal organs and graft bearing muscle were retrieved, and the radioactive uptake measured in a well counter within 10 minutes. The specific uptake in native and transplanted islets was assessed by autoradiography. The total insulin-positive area of the islet grafts was determined by immunohistochemistry. Results Intramuscular islet grafts could easily be visualized by this tracer, and the background uptake was very low. There was a linear correlation between the radioactivity uptake and the number of transplanted islets, both for standardized uptake values and the total radiotracer uptake in each graft (percentage of injected dose). The quantified total insulin area of surviving β cells showed an even stronger correlation to both standardized uptake values (R = 0.96, P = 0.0002) and percentage of injected dose (R = 0.88, P = 0.0095). There was no correlation to estimated α cell mass. Conclusions [177Lu]DO3A-VS-Cys40-Exendin-4 could be used to quantify β-cell mass after experimental intramuscular islet transplantation. This technique may well be transferred to the clinical setting by exchanging Lutetium-177 radionuclide to a positron emitting Gallium-68.

  20. Assessment of human natural killer and lymphokine-activated killer cell cytotoxicity against Toxoplasma gondii trophozoites and brain cysts

    Energy Technology Data Exchange (ETDEWEB)

    Dannemann, B.R.; Morris, V.A.; Araujo, F.G.; Remington, J.S. (Palo Alto Medical Foundation, CA (USA))

    1989-10-15

    Because previous work has suggested that NK cells may be important in host resistance against the intracellular parasite Toxoplasma gondii we examined whether human NK cells and lymphokine-activated killer (LAK) cells have activity against trophozoites and cysts of this organism in vitro. A method to radiolabel Toxoplasma trophozoites with 51Cr was developed and direct cytotoxic activity was determined by using modifications of the standard 51Cr release assay. Viability of 51Cr-labeled trophozoites assessed by both methylene blue staining and trypan blue exclusion was greater than 90%. Significantly more 51Cr was released by anti-Toxoplasma antibody and C than by antibody in the absence of C. Incubation of trophozoites with freshly isolated human NK cells or NK cells activated with either rIL-2 or rIFN-alpha did not result in significant release of 51Cr (specific lysis was 0 to 2.3%). In contrast, the average specific lysis of radiolabeled trophozoites by LAK cells was significant. In a series of separate experiments, preincubation of radiolabeled trophozoites with heat-inactivated normal or Toxoplasma antibody-positive human serum increased the cytotoxicity of LAK cells from a mean specific lysis of 15% +/- 4.5 to 39% +/- 8.5, respectively, as assessed by 51Cr release. Because previous work has shown that radioisotope release from parasites may be nonspecific, separate experiments were performed to determine the cytotoxicity of LAK cells against antibody-coated trophozoites by using ethidium bromide-acridine orange staining to assess effector cell damage. LAK cells had a mean specific lysis of 51% against antibody-coated trophozoites by ethidium bromide-acridine orange staining. Preincubation with heat-inactivated Toxoplasma-antibody positive human serum did not increase activity of rIL-2-activated NK cells against 51CR-labeled trophozoites.

  1. Effect of immunologic reactions on rat intestinal epithelium. Correlation of increased permeability to chromium 51-labeled ethylenediaminetetraacetic acid and ovalbumin during acute inflammation and anaphylaxis

    Energy Technology Data Exchange (ETDEWEB)

    Ramage, J.K.; Stanisz, A.; Scicchitano, R.; Hunt, R.H.; Perdue, M.H.

    1988-06-01

    In these studies we compared jejunal permeability to two probes--chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) (mol wt, 360) and ovalbumin (mol wt, 45,000)--under control conditions, during acute intestinal inflammation, and in response to systemic anaphylaxis. Acute inflammation was produced after infection with Nippostrongylus brasiliensis and rats were studied at day 0 (control), day 4 (early), day 10 (acute), and day 35 (postinfection). At the latter stage, immune rats were also studied during anaphylaxis induced by i.v. N. brasiliensis antigen. In each study, blood and urine were sampled over 5 h after the probes were simultaneously injected into ligated loops in anesthetized rats. In controls, small quantities (less than 0.04% and 0.002% of the administered dose for 51Cr-EDTA and ovalbumin, respectively) appeared in the circulation and plateaued at 1 h. During acute inflammation, the appearance of both probes continued to increase with time. Compared with controls, 5-h values for 51Cr-EDTA and ovalbumin were (a) significantly elevated at day 4 (p less than 0.005), (b) increased approximately 20-fold at day 10 (p less than 0.005 and less than 0.01, respectively), and (c) normal at day 35. Urinary recovery of 51Cr-EDTA followed the same pattern. During anaphylaxis, appearance of the probes in the circulation increased at 1 h to values approximately 10-fold those in controls (p less than 0.001 and less than 0.01, for 51Cr-EDTA and ovalbumin, respectively), and then declined. Urinary recovery of 51Cr-EDTA over 5 h was also significantly increased. We conclude that epithelial barrier function becomes impaired during both acute inflammation and anaphylaxis. In this rat model, gut permeability changes to 51Cr-EDTA reflect gut permeability changes to macromolecular antigens.

  2. Radiometric and spectrophotometric studies of the behavior of chromium(VI) oxide in concentrated perchloric acid

    Energy Technology Data Exchange (ETDEWEB)

    Pezzin, S.H.; Collins, C.H.; Collins, K.E. [Universidade Estadual de Campinas (Brazil). Inst. de Quimica; Archundia, C. [Universidad Nacional Autonoma de Mexico, Mexico City (Mexico). Inst. de Ciencias Nucleares

    1997-11-01

    A study of the behavior of {sup 51}CrO{sub 3} in 70% HClO{sub 4} over the temperature range from 20 to 194 C by means of Cr-51 labelling, UV-VIS spectrophotometry and ion exchange chromatography, shows that the solubility of {sup 51}CrO{sub 3} depends on a competition between the dissolution process and the acid reduction of solution phase Cr(VI). These processes occur simultaneously and are dependent on both the temperature and the concentration of Cr(VI), as shown by comparison between radiometric measurements (where total chromium can be accurately determined) and spectrophotometric measurements (where only the Cr(VI) is detectable at the wavelengths studied). These conclusions are confirmed by PbCrO{sub 4} precipitation of {sup 51}Cr(VI), where at 194 C, 97% of the total chromium appears as Pb{sup 51}CrO{sub 4} while at 86 C only 5% does. Cation exchange chromatography of the solution after brief contact of {sup 51}CrO{sub 3} with concentrated HClO{sub 4} at 20 C shows only traces of {sup 51}Cr(VI), most of the radioactivity eluting as {sup 51}Cr(H{sub 2}O){sup 3+}{sub 6}, with smaller amounts of species with +2 and +1 charges. These results imply serious limitations to the spectrophotometric determination of low concentrations of total chromium in alloys or in biological material which use dissolution in 70% HClO{sub 4} as a primary analytical step. (orig.)

  3. In vitro and in vivo evaluation of direct rhenium-188-labeled anti-CD52 monoclonal antibody alemtuzumab for radioimmunotherapy of B-cell chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Decker, Mario de [Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent (Belgium); Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen (Netherlands)], E-mail: mario.dedecker@health.wa.gov.au; Bacher, Klaus; Thierens, Hubert [Department of Medical Physics and Radiation Protection, Ghent University, Ghent (Belgium); Slegers, Guido [Department of Medical Imaging of Domestic Animals, Ghent University, Ghent (Belgium); Dierckx, Rudi A. [Department of Nuclear Medicine and Molecular Imaging, University Medical Centre Groningen, Groningen (Netherlands); Vos, Filip de [Department of Radiopharmacy, Faculty of Pharmaceutical Sciences, Ghent University, Ghent (Belgium)

    2008-07-15

    Alemtuzumab (Campath, Berlex) is a humanized IgG1 rat monoclonal antibody directed against the cell surface CD52 antigen, found on lymphocytes and monocytes. It is being developed for the treatment of chronic lymphocytic leukemia (CLL), autoimmune disease and for the prevention of transplant rejection. This study focused on synthesis, quality control, in vitro evaluation and biodistrubution of {sup 188}Re-labeled alemtuzumab for radioimmunotherapy of B-cell CLL. {sup 188}Re-alemtuzumab was synthesized using a direct radiolabeling method. Reduction of the intramolecular disulfide bonds of the antibody was performed with tris-(carboxyethyl)-phosphine (Pierce), using a 1:60 molar excess. Reaction took place at room temperature for 20 min. A PD-10 desalting column was used to purify the reduced antibody from excess phospine. Complexation and transchelation of {sup 188}ReO{sub 4}{sup -} was achieved using sodium gluconate as weak chelator and SnCl{sub 2} as reducing agent. Quality control was done using instant thin-layer chromatography. Binding assays were performed on a CD52-positive cell line (HuT-78). Female NMRI mice were injected intravenously with 20 {mu}g radiolabeled alemtuzumab and killed at preset time intervals for biodistribution studies. Tissues were dissected, weighed and counted for determination of radioactivity. Data were expressed as percentage injected activity per gram of tissue (% IA/g tissue) or as percentage injected activity (% IA). {sup 188}Re-alemtuzumab was prepared achieving high radiochemical yields. Labeling efficiency of more than 95% can be obtained using optimal reaction conditions. {sup 188}Re-alemtuzumab showed good in vitro stability, remaining intact at 24 h after radiolabeling. In mice, {sup 188}Re-alemtuzumab showed high uptake in the blood (25.10{+-}1.36% IA at 1 h p.i.), followed by a biexponential clearance (t{sub 1/2{alpha}}=4.790 h and t{sub 1/2{beta}}=55.45 h). Increased uptake was observed in kidneys and heart (9

  4. Targeted killing of virally infected cells by radiolabeled antibodies to viral proteins.

    Directory of Open Access Journals (Sweden)

    Ekaterina Dadachova

    2006-11-01

    Full Text Available BACKGROUND: The HIV epidemic is a major threat to health in the developing and western worlds. A modality that targets and kills HIV-1-infected cells could have a major impact on the treatment of acute exposure and the elimination of persistent reservoirs of infected cells. The aim of this proof-of-principle study was to demonstrate the efficacy of a therapeutic strategy of targeting and eliminating HIV-1-infected cells with radiolabeled antibodies specific to viral proteins in vitro and in vivo. METHODS AND FINDINGS: Antibodies to HIV-1 envelope glycoproteins gp120 and gp41 labeled with radioisotopes bismuth 213 ((213Bi and rhenium 188 ((188Re selectively killed chronically HIV-1-infected human T cells and acutely HIV-1-infected human peripheral blood mononuclear cells (hPBMCs in vitro. Treatment of severe combined immunodeficiency (SCID mice harboring HIV-1-infected hPBMCs in their spleens with a (213Bi- or (188Re-labeled monoclonal antibody (mAb to gp41 resulted in a 57% injected dose per gram uptake of radiolabeled mAb in the infected spleens and in a greater than 99% elimination of HIV-1-infected cells in a dose-dependent manner. The number of HIV-1-infected thymocytes decreased 2.5-fold in the human thymic implant grafts of SCID mice treated with the (188Re-labeled antibody to gp41 compared with those treated with the (188Re-control mAb. The treatment did not cause acute hematologic toxicity in the treated mice. CONCLUSIONS: The current study demonstrates the effectiveness of HIV-targeted radioimmunotherapy and may provide a novel treatment option in combination with highly active antiretroviral therapy for the eradication of HIV.

  5. Radiobiological characterization of post-lumpectomy focal brachytherapy with lipid nanoparticle-carried radionuclides

    Science.gov (United States)

    Hrycushko, Brian A.; Gutierrez, Alonso N.; Goins, Beth; Yan, Weiqiang; Phillips, William T.; Otto, Pamela M.; Bao, Ande

    2011-02-01

    Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. The primary objective of this work was to characterize, through dosimetric and radiobiological modeling, a novel focal brachytherapy technique which uses direct intracavitary infusion of β-emitting radionuclides (186Re/188Re) carried by lipid nanoparticles (liposomes). Absorbed dose calculations were performed for a spherical lumpectomy cavity with a uniformly injected activity distribution using a dose point kernel convolution technique. Radiobiological indices were used to relate predicted therapy outcome and normal tissue complication of this technique with equivalent external beam radiotherapy treatment regimens. Modeled stromal damage was used as a measure of the inhibition of the stimulatory effect on tumor growth driven by the wound healing response. A sample treatment plan delivering 50 Gy at a therapeutic range of 2.0 mm for 186Re-liposomes and 5.0 mm for 188Re-liposomes takes advantage of the dose delivery characteristics of the β-emissions, providing significant EUD (58.2 Gy and 72.5 Gy for 186Re and 188Re, respectively) with a minimal NTCP (0.046%) of the healthy ipsilateral breast. Modeling of kidney BED and ipsilateral breast NTCP showed that large injected activity concentrations of both radionuclides could be safely administered without significant complications.

  6. Thermal neutron fluence from ultra low-level gamma-ray spectrometry of spoons activated during the JCO criticality accident at Tokai-mura in 1999.

    Science.gov (United States)

    Hult, Mikael; Martínez Canet, María Jose; Johnston, Peter N; Komura, Kazuhisa

    2002-01-01

    During the JCO-accident in Tokai-mura in 1999, the surrounding village was irradiated by an uncontrolled neutron flux. At some locations in that village, the thermal neutron flux was determined retrospectively by measurement of the very low activity of 51Cr and 60Co in stainless-steel spoons using gamma-ray spectrometry in underground laboratories. Activities determined in the HADES underground facility are presented here, together with calibrations performed using a well-defined thermal neutron flux to directly estimate the fluence of thermal neutrons independent of most assumptions. The results show measurable 51Cr in three samples and 60Co in four samples taken from locations at distances of up to 430m from the accident location despite the elapse of 4 half-lives of 51Cr before measurement. Effects of air transport of the samples were considered and shown to be negligible.

  7. Glomerular filtration rate by {sup 51}chomium and {sup 113m}indium labeled EDTA in horses; Taxa de filtracao glomerular pelo EDTA marcado com {sup 51}cromo e com {sup 113m}indio em equinos

    Energy Technology Data Exchange (ETDEWEB)

    Maliska, C.; D' Almeida, J.; Pellegrini, P.M.; Schimit, T.S. [Hospital Central do Exercito (HCE), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear; Pinho, W.R. [Centro de Ensino Superior, Valenca, RJ (Brazil). Fac. de Medicina Veterinaria; Lima, J.E.T. [Instituto Nacional do Cancer (INCa), Rio de Janeiro, RJ (Brazil). Servico de Medicina Nuclear

    2009-07-01

    The glomerular filtration rate was determined in nine healthy horses, six male and three female, aged two to 12-year-old, by means of {sup 51}Cr and {sup 113m}In labeled EDTA single injection technique. The glomerular filtration rate was calculated from the plasma disappearance curve and the volume of distribution of the radiotracer, {sup 51}Cr-EDTA or {sup 113m}In-EDTA. The result (mean +- standard deviation) was 148.80 +- 26.42 m L.min{sup -1}.100 kg. It is concluded that the measurement of glomerular filtration rate by {sup 51}Cr-EDTA or {sup 113m}In-EDTA by single injection technique eliminates the bladder catheterization, and for its simplicity, convenience, accuracy, and low dose of radiation, can be used in horses as a method of choice in clinical routine. (author)

  8. Plasma volume changes during hypoglycaemia

    DEFF Research Database (Denmark)

    Hilsted, J; Bendtsen, F; Christensen, N J

    1990-01-01

    To investigate whether previously reported changes in venous blood volume and composition induced by acute hypoglycaemia in humans are representative for the entire body we measured erythrocyte 51Cr content, haematocrit, plasma volume, intravascular albumin content and transcapillary escape rate...... of albumin in arterial and venous blood in seven healthy subjects before and during insulin-induced hypoglycaemia. In both vascular sites blood 51Cr content and the haematocrit increased, plasma volume and intravascular albumin content decreased and the transcapillary escape rate of albumin increased during...

  9. Tissue distribution of adoptively transferred adherent lymphokine-activated killer cells assessed by different cell labels

    DEFF Research Database (Denmark)

    Basse, P; Herberman, R B; Hokland, M;

    1992-01-01

    Assessment of the tissue distribution of adoptively transferred adherent lymphokine-activated killer A-LAK) cells by use of 51Cr indicated that these effector cells, after an initial phase in the lungs, distributed in high numbers to liver and spleen (30% and 10% of injected dose, respectively......). However, when this experiment was repeated with 125IdUrd as cell label, fewer than 2% and 0.5% of the injected cells distributed into liver and spleen respectively. To analyse this discrepancy, we compared the tissue distribution of 51Cr- and 125IdUrd-labelled A-LAK cells with that indicated...

  10. Activation cross-sections of longer lived products of proton induced nuclear reactions on cobalt up to 70 MeV

    CERN Document Server

    Ditrói, F; Takács, S; Hermanne, A; Yamazaki, H; Baba, M; Mohammadi, A

    2013-01-01

    As a part of our series of studies on deuteron induced reaction on various target materials excitation functions on natural cobalt have been measured by using stacked-foil technique. In these measurements 51Cr, 55;56;57;58Co, 51Cr, 52;54;56Mn and 56;57Ni radioisotopes have been identi?fied. For the above isotopes the excitation functions were determined and compared with the literature data and with the results of EMPIRE and TALYS calculations taken from the TENDL 2011 library. The agreement with previous measurements was acceptable and we could also determine new cross-section data.

  11. Whole-body microvascular permeability of small molecules in man

    DEFF Research Database (Denmark)

    Henriksen, J H

    1985-01-01

    In order to estimate whole-body permeability-surface area (PS) product, the initial slope of the plasma disappearance curve was determined after simultaneous i.v. injection of 24Na+ (mol.wt 24) and 51Cr-EDTA (mol.wt 342). Twelve subjects were studied. Plasma volume (PV) was measured by the indica......In order to estimate whole-body permeability-surface area (PS) product, the initial slope of the plasma disappearance curve was determined after simultaneous i.v. injection of 24Na+ (mol.wt 24) and 51Cr-EDTA (mol.wt 342). Twelve subjects were studied. Plasma volume (PV) was measured...

  12. Standardization of (55)Fe by tracing method.

    Science.gov (United States)

    Koskinas, M F; Pires, C A; Yamazaki, I M; Silva, E A; Dias, M S

    2008-01-01

    This work describes the procedure followed by the Laboratório de Metrologia Nuclear (LMN) for the standardization of (55)Fe by the tracing method. This technique was applied using two radionuclides, which decay by the electron capture process followed by a prompt gamma-ray, namely (51)Cr and (54)Mn, as tracers. The calibration was performed in a 4pibeta-gamma coincidence system. The efficiency was obtained by selecting a gamma-ray window set at the 320keV total absorption peak for (51)Cr and at 834keV for (54)Mn.

  13. Study of conjugation and radiolabeling of monoclonal antibody rituximab for use in radionuclide therapy; Estudo da conjugacao e radiomarcacao do anticorpo monoclonal rituximab para aplicacao em terapia radionuclidica

    Energy Technology Data Exchange (ETDEWEB)

    Massicano, Adriana Vidal Fernandes

    2011-07-01

    Lymphomas are tumors originated from the transformation of a lymphocyte in the lymphatic system. The most common lymphoma is the Non-Hodgkin Lymphoma (NHL). Advances in immunology and molecular biology have been improving NHL's detection and treatment strategies development, such as Radioimmunotherapy (RIT). Rituximab is an anti-CD20 monoclonal antibody used as immunotherapeutic to treat refractory or relapsed NHL. The goal of the present work was to conjugate this antibody to DOTA-NHS-ester bifunctional chelator and to radiolabel it with {sup 177}Lu radioisotope in order to develop a radio immunotherapeutic agent for NHL's treatment. Different rituximab to DOTA molar ratios (1:5, 1:10, 1:20, 1:50, 1:250, 1:500 and 1:1000) were evaluated in order to determine the best condition for obtaining the highest radiochemical purity of radio immunotherapeutic. The stability of the unlabeled immuno conjugated was evaluated by high performance liquid chromatography (HPLC) for up to 240 days in different storage conditions. The stability of the labeled preparations was evaluated either after storing at 2-8 degree C or incubation in human serum at 37 degree C. The binding to serum proteins was also determined. In vivo studies were performed in healthy Swiss mice, in order to characterize the biological properties of labeled conjugate. Finally, preliminary studies of radio immuno conjugated competitive binding to CD20 positive Raji cells were carried out in order to analyze if the process of conjugation and radiolabeling compromises the immunoreactivity of the antibody. The conjugation applying lower antibody to chelator molar ratios (1:5, 1:10 and 1:20) showed high stability when stored for up to 240 days in different conditions. The HPLC analysis showed that the monoclonal antibody conjugated in molar ratio 1:50 was labeled with higher radiochemical purity (> 95%) when purified in PD-10 column. This conjugate showed reasonable stability at 2-8 degree C. The analysis

  14. Pharmacokinetics and Dosimetry Studies for Optimization of Pretargeted Radioimmunotherapy in CEA-Expressing Advanced Lung Cancer Patients

    Directory of Open Access Journals (Sweden)

    Caroline eBodet-Milin

    2015-11-01

    Full Text Available Objectives. A phase I pretargeted radioimmunotherapy trial (EudractCT 200800603096 was designed in patients with metastatic lung cancer expressing carcinoembryonic antigen (CEA to optimize bispecific antibody and labelled peptide doses, as well as the delay between their injections.Methods. Three cohorts of 3 patients received the anti-CEA x anti-histamine-succinyl-glycine (HSG humanized trivalent bispecific antibody (TF2 and the IMP288 bivalent HSG-peptide. Patients underwent a pre-therapeutic imaging session S1 (44 or 88 nmol/m2 of TF2 followed by 4.4 nmol/m2, 185 MBq, of 111In-labelled IMP288, and, 1-2 weeks later, a therapy session S2 (240 or 480 nmol/m2 of TF2 followed by 24 nmol/m2, 1.1 GBq/m2, 177Lu-labeled IMP288. The pretargeting delay was 24 or 48 hours. The dose schedule was defined based on pre-clinical TF2 pharmacokinetic studies, on our previous clinical data using the previous anti-CEA pretargeting system and on clinical results observed in the first patients injected using the same system in the Netherlands.Results. TF2 pharmacokinetics (PK was represented by a two-compartment model in which the central compartment volume was linearly dependent on the patient's surface area. PK were remarkably similar, with a clearance of 0.33 +/- 0.03 L/h per m2. 111In- and 177Lu-IMP288 PK were also well represented by a two-compartment model. IMP288 PK were faster (clearance 1.4 to 3.3 l/h. The central compartment volume was proportional to body surface area and IMP288clearance depended on the molar ratio of injected IMP288 to circulating TF2 at the time of IMP288 injection. Modelling of image quantification confirmed the dependence of IMP288 kinetics on circulating TF2, but tumour activity PK were variable. Organ absorbed doses were not significantly different in the 3 cohorts, but the tumour dose was significantly higher with the higher molar doses of TF2 (p < 0.002. S1 imaging predicted absorbed doses calculated in S2. Conclusion. The best

  15. Three-dimensional radiobiological dosimetry of kidneys for treatment planning in peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Baechler, Sebastien; Hobbs, Robert F.; Boubaker, Ariane; Buchegger, Franz; He Bin; Frey, Eric C.; Sgouros, George [Institute of Radiation Physics, Lausanne University Hospital, 1007 Lausanne (Switzerland); Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231 (United States); Department of Nuclear Medicine, Lausanne University Hospital, 1011 Lausanne (Switzerland); Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21231 (United States)

    2012-10-15

    Purpose: Peptide receptor radionuclide therapy (PRRT) delivers high absorbed doses to kidneys and may lead to permanent nephropathy. Reliable dosimetry of kidneys is thus critical for safe and effective PRRT. The aim of this work was to assess the feasibility of planning PRRT based on 3D radiobiological dosimetry (3D-RD) in order to optimize both the amount of activity to administer and the fractionation scheme, while limiting the absorbed dose and the biological effective dose (BED) to the renal cortex. Methods: Planar and SPECT data were available for a patient examined with {sup 111}In-DTPA-octreotide at 0.5 (planar only), 4, 24, and 48 h post-injection. Absorbed dose and BED distributions were calculated for common therapeutic radionuclides, i.e., {sup 111}In, {sup 90}Y and {sup 177}Lu, using the 3D-RD methodology. Dose-volume histograms were computed and mean absorbed doses to kidneys, renal cortices, and medullae were compared with results obtained using the MIRD schema (S-values) with the multiregion kidney dosimetry model. Two different treatment planning approaches based on (1) the fixed absorbed dose to the cortex and (2) the fixed BED to the cortex were then considered to optimize the activity to administer by varying the number of fractions. Results: Mean absorbed doses calculated with 3D-RD were in good agreement with those obtained with S-value-based SPECT dosimetry for {sup 90}Y and {sup 177}Lu. Nevertheless, for {sup 111}In, differences of 14% and 22% were found for the whole kidneys and the cortex, respectively. Moreover, the authors found that planar-based dosimetry systematically underestimates the absorbed dose in comparison with SPECT-based methods, up to 32%. Regarding the 3D-RD-based treatment planning using a fixed BED constraint to the renal cortex, the optimal number of fractions was found to be 3 or 4, depending on the radionuclide administered and the value of the fixed BED. Cumulative activities obtained using the proposed simulated

  16. 10 CFR 30.71 - Schedule B.

    Science.gov (United States)

    2010-01-01

    ...) 10 Chlorine 38 (Cl 38) 10 Chromium 51 (Cr 51) 1,000 Cobalt 57 (Co 57) 100 Cobalt 58m (Co 58m) 10 Cobalt 58 (Co 58) 10 Cobalt 60 (Co 60) 1 Copper 64 (Cu 64) 100 Dysprosium 165 (Dy 165) 10 Dysprosium...

  17. 10 CFR Appendix L to Part 110 - Illustrative List of Byproduct Materials Under NRC Export/Import Licensing Authority a

    Science.gov (United States)

    2010-01-01

    ... 137) Chlorine 36 (Cl 36) Chlorine 38 (Cl 38) Chromium 51 (Cr 51) Cobalt 58m (Co 58m) Cobalt 58 (Co 58) Cobalt 60 (Co 60) Copper 64 (Cu 64) Curium 240 (Cm 240) Curium 241 (Cm 241) Curium 242 (Cm 242)...

  18. Drug: D06891 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available D06891 Drug Chromium Cr 51 Edetate (USP) C10H16N2O8. xCr D06891.gif ATC code: V09CX...TICALS V09C RENAL SYSTEM V09CX Other renal system diagnostic radiopharmaceuticals V09CX04 Chromium (51Cr) edetate D06891 Chromium

  19. One-sample determination of glomerular filtration rate (GFR) in children. An evaluation based on 75 consecutive patients

    DEFF Research Database (Denmark)

    Henriksen, Ulrik Lütken; Kanstrup, Inge-Lis; Henriksen, Jens Henrik Sahl

    2013-01-01

    Abstract Background and aim. From a clinical point of view determination of glomerular filtration rate (clearance) is important. The aim of the present study was to compare the one-sample clearance to reference multiple-sample (51)Cr-EDTA clearance in consecutively referred children suspected of ...

  20. Rapid decline in glomerular filtration rate during the first weeks following heart transplantation

    DEFF Research Database (Denmark)

    Hornum, M; Andersen, M; Gustafsson, F;

    2011-01-01

    We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using (51)Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before...

  1. Changes in glomerular filtration rate, lithium clearance and plasma protein clearances in the early phase after unilateral nephrectomy in living healthy renal transplant donors

    DEFF Research Database (Denmark)

    Strandgaard, S; Kamper, A; Skaarup, P;

    1988-01-01

    1. Glomerular and tubular function was studied before and 2 months after unilateral nephrectomy in 14 healthy kidney donors by measurement of the clearances of 51Cr-labelled ethylenediaminetetra-acetate, lithium, beta 2-microglobulin, albumin and immunoglobulin G. 2. The glomerular filtration rate...

  2. Monitoring kidney function in type 2 diabetic patients with incipient and overt diabetic nephropathy

    DEFF Research Database (Denmark)

    Rossing, Peter; Rossing, Kasper; Gaede, Peter

    2006-01-01

    The purpose of this study was to assess agreement between glomerular filtration rate (GFR) and the decline in GFR estimated with the Modification of Diet in Renal Disease (MDRD) Study Group equation or the Cockcroft-Gault formula and measured by the plasma clearance of 51Cr-EDTA....

  3. The influence of body posture on lithium clearance

    DEFF Research Database (Denmark)

    Kamper, A L; Strandgaard, S; Holstein-Rathlou, N H;

    1988-01-01

    To establish appropriate standard circumstances for lithium clearance measurements, a study was undertaken in 12 healthy volunteers. In each subject, the glomerular filtration rate (GFR), as estimated by [51Cr]EDTA plasma clearance, and the renal clearances of lithium, sodium and potassium were m...

  4. Drug: D05252 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available odium chromate (51Cr) (INN); Rachromate (TN) CrO4. 2Na 160.904 161.9732 D05252.gif Diagnostic aid [blood volume determination]; Radio...br08301] 4 Agents affecting cellular function 43 Radioactive drugs 430 Radioactive drugs 4300 Radio

  5. Omega 3 fatty acids increase spontaneous release of cytosolic components from tumor cells

    Energy Technology Data Exchange (ETDEWEB)

    Jenski, L.J.; Sturdevant, L.K.; Ehringer, W.D.; Stillwell, W. (Department of Biology, Indiana University-Purdue University, Indianapolis (United States))

    1991-05-01

    Mice fed menhaden (fish) oil or coconut oil-rich diets were inoculated intraperitoneally with a rapidly growing leukemia, T27A. After one week, the tumor cells were harvested, and 51Cr was used to label intracellular molecules. Spontaneous release of 51Cr was used as a measure of plasma membrane permeability. Compared to cells from mice fed coconut oil (rich in saturated fatty acids), tumor cells from mice fed menhaden oil (rich in long chain polyunsaturated omega 3 fatty acids) showed an increased level of spontaneous 51Cr release, which was exacerbated by increased temperature and reduced by extracellular protein. At physiological salt concentrations, the released 51Cr was detected in particles of approximately 2700 daltons. Enhanced permeability correlated with the incorporation of dietary (fish oil) omega 3 polyunsaturated fatty acids docosahexaenoic and eicosapentaenoic acid into the tumor cells. The results demonstrate that omega 3 fatty acids are incorporated into cellular constituents of tumor cells and change properties associated with the plasma membrane. This result suggests that dietary manipulation may be used to enhance tumor cell permeability and contribute to tumor eradication.

  6. The renal handling of sodium and water is not affected by the standard-dose cisplatin treatment for testicular cancer

    DEFF Research Database (Denmark)

    Daugaard, G; Strandgaard, S; Holstein-Rathlou, N H

    1987-01-01

    Renal clearances of 51Cr-EDTA, lithium, sodium and potassium were measured before and after each of four consecutive treatment series with cisplatin in 15 men with testicular cancer. Since lithium is reabsorbed like sodium and water in the proximal tubules, but not reabsorbed to any measurable...

  7. Active and passive vectorization of technetium{sup 99m} and {sup 188}rhenium radiopharmaceuticals for medical imaging and radiotherapy; Vectorisations active et passive de radiopharmaceutiques du technetium-99m et du rhenium-188 pour l'imagerie medicale et la therapie

    Energy Technology Data Exchange (ETDEWEB)

    Lepareur, N

    2003-11-15

    Research for new molecules for nuclear medicine is a field in constant development. Over the past few years, development of new radiopharmaceuticals for radiotherapy has renewed interest for rhenium chemistry. Indeed, its two isotopes {sup 186}Re and {sup 188}Re, owing to their ideal properties and their similitude with {sup 99m}Tc, which is widely used as a radiotracer for diagnostic imaging, seem very promising for the preparation of radiopharmaceuticals. In the first part of this manuscript, the synthesis of rhenium and technetium-99 complexes, [M(RPhCS3)2(RPhCS2)] (M = Re, Tc), is described. The preparation of technetium{sup 99m} based radiopharmaceuticals, analogues to the pondered complexes, is also described. The stability/reactivity of these complexes has been studied by exchange reactions with potential ligands, specially dithiocarbamates, and also by UV-visible absorption spectroscopy and thermogravimetry. The reactivity of the complexes towards dithiocarbamates leads to the possibility to bind biomolecules to the metallic core, via the dithiocarbamate moiety. This method represents a potential alternative to current ones using the so-called bifunctional approach. In the second part of this manuscript, a new kit formulation for the {sup 188}Re labeling of lipiodol is described, using a complex analogous to those described in the previous part. The labeled oil is a potential cure for hepatocellular carcinoma. The in vitro and in vivo stability of this {sup 188}Re-SSS lipiodol and of its analogue {sup 99m}Tc-SSS lipiodol has been studied, and also their in vivo behavior in healthy pigs. This study has shown the quasi-exclusive hepatic fixation of the radiopharmaceutical, and has proven its good stability. Its selectivity for tumors remains to be shown before trying it on humans. (author)

  8. Radiolabeling of anti-CD20 with Re-188 for treatment of non-Hodgkin's lymphoma: radiochemical control

    Energy Technology Data Exchange (ETDEWEB)

    Dias, Carla R.; Osso Junior, Joao A., E-mail: carladias@usp.b, E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    The development of tumor-selective radiopharmaceuticals is clinically desirable as a means of detecting or confirming the presence and location of primary and metastatic lesions and monitoring tumor response to (chemo)therapy. In addition, the application of targeted radiotherapeutics provides a unique and effective modality for direct tumor treatment. In this manner the radioimmunotherapy (RIT) uses the targeting features of monoclonal antibody to deliver radiation from an attached radionuclide. Antibody therapy directed against the CD20 antigen on the surface of B-cells is considered one of the first successful target-specific therapies in oncology. The radionuclide rhenium-188 ({sup 188}Re) is currently produced from the father nuclide tungsten-188 ({sup 188}W) through a transportable generator system. Because of its easy availability and suitable nuclear properties (EbetaMAX = 2.1 MeV, t{sub 1/2} = 16.9 h, Egamma = 155 keV), this radionuclide is considered an attractive candidate for application as therapeutic agent and could be conveniently utilized for imaging and dosimetric purposes. The purpose of this work is to show the radiochemical control of the optimized formulation (solution) and lyophilized formulation (kit) of labeled rituximab (anti-CD20) with {sup 188}Re. Rituximab was reduced by incubation with 2-mercaptoethanol at room temperature. The number of resulting free sulfhydryl groups was assayed with Ellman's reagent. Radiochemical purity of {sup 188}Re-rituximab was evaluated using instant thin layer chromatography-silica gel (ITLC-SG). Quality control methods for evaluation of radiochemical purity showed good labeling yield of the antibody. (author)

  9. Comparative characterization of the leukocidic and hemolytic activity of Moraxella bovis.

    Science.gov (United States)

    Hoien-Dalen, P S; Rosenbusch, R F; Roth, J A

    1990-02-01

    The cytotoxic effect of Moraxella bovis 118F on bovine neutrophils was evaluated and characterized by use of a 51Cr release assay. Neutrophils harvested from healthy adult cattle were labeled with 51Cr. The leukocidic activity produced by M bovis 118F, a hemolytic strain of M bovis, was heat-labile. A live culture of strain 118F, at a ratio of 100 bacteria/neutrophil, released 97.7% of the 51Cr from labeled neutrophils. Neither a heat-killed preparation of M bovis 118F nor a live or heat-killed preparation of M bovis IBH63 (a nonhemolytic and nonpathogenic strain) induced significant (P greater than 0.05) release of 51Cr. Moraxella bovis 118F broth culture filtrates prepared for evaluation of leukocidic activity also were evaluated for hemolytic activity. These 2 toxic activities had several characteristics in common. Both were filterable, heat-labile, produced by a hemolytic strain, and were released during early logarithmic phase growth from broth cultures. Leukocidic and hemolytic activities were protected from degradation by phenylmethyl sulfonyl fluoride, a serine protease inhibitor. Leukocidic and hemolytic activities were dependent on calcium ions. Filtrate resulted in 54.1% 51Cr release from labeled neutrophils and contained 646.7 hemolytic U/ml, respectively, when saline (0.85% NaCl) + 10 mM CaCl2 solution was used as diluent. Neither saline solution nor saline + 10 mM MgCl2 solution supported leukocidic or hemolytic activity. Serum, obtained from several calves 10 to 38 days after M bovis inoculation, substantially neutralized leukocidic and hemolytic activities, compared with paired preinoculation serum samples.(ABSTRACT TRUNCATED AT 250 WORDS)

  10. Evaluation of tetrazolium-based semiautomatic colorimetric assay for measurement of human antitumor cytotoxicity

    Energy Technology Data Exchange (ETDEWEB)

    Heo, D.S.; Park, J.G.; Hata, K.; Day, R.; Herberman, R.B.; Whiteside, T.L. (Univ. of Pittsburgh School of Medicine, PA (USA))

    1990-06-15

    A 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)-based colorimetric assay was developed and compared with 51Cr release from different adherent tumor cell targets (human squamous cell carcinoma lines of the head and neck established in our laboratory, melanoma, and colorectal carcinoma) using 5-7-day human lymphokine-activated killer cells and monocyte-depleted peripheral blood lymphocytes as effectors. With adherent tumor cell targets, MTT colorimetry was more sensitive than the 51Cr release assay in measuring the antitumor activity of effectors: median, 4385 (range, 988-8144) versus median, 1061 (range, 582-7294) lytic units (the number of effector cells required to lyse 20% of 5 x 10(3) targets)/10(7) effectors (P less than 0.01). Background effects (without effector cells) were comparable in 4-h assays (9% versus 10%) between MTT colorimetry and 51Cr release. In 24-h assays, MTT colorimetry showed higher antitumor activity (70-100% versus 40-60% lysis at 1:1 effector:target cell ratio) but lower background effects (6% versus 38%) than 51Cr release assay. Thus, MTT colorimetry was more sensitive, did not use radiolabeled targets, required fewer effector cells, and was easier, less expensive, and better adaptable to serial monitoring of effector cell function in cancer patients. This colorimetric assay is especially well suited to adherent tumor cell targets. The use of adherent tumor cell monolayers, as opposed to trypsinized single cell suspensions, provides an opportunity to measure interactions of effector cells with enzymatically unaltered solid tumor targets. Because of the greater sensitivity of the colorimetric assay, the transformation of MTT data into lytic units, as commonly used for 51Cr release assays, required an adjustment to avoid the extrapolation based on the exponential fit equation.

  11. Targeting somatostatin receptors in gastro entero pancreatic neuroendocrine tumours (G.E.P.N.E.T.): Which radiotracers for which tumours?;Ciblage des recepteurs de la somatostatine dans les tumeurs neuroendocrines gastroenteropancreatiques (TNE-GEP): quels radiotraceurs pour quelles tumeurs?

    Energy Technology Data Exchange (ETDEWEB)

    Cuny, T.; Saveanu, A.; Barlier, A. [CRN2M, UMR 6231, CNRS, laboratoire de neurobiologie et neurophysiologie de Marseille, faculte de medecine, 13 - Marseille (France); Saveanu, A.; Barlier, A. [Hotal de la Conception Assistance publique-hopitaux de Marseille, Laboratoire de biochimie, biologie moleculaire, 13 - Marseille (France); Taieb, D. [Hopital de la Timone, Assistance publique des hopitaux de Marseille, Service de medecine nucleaire, 13 - Marseille (France)

    2010-05-15

    Topographic and functional imaging hold a key position in endocrine oncology. In vivo somatostatin receptor scintigraphy using Indium-111 labeled DTPA-octreotide, a tracer with preferential affinity for the somatostatin receptor subtype 2 (sst2), is the gold-standard for initial diagnosis of gastro entero pancreatic neuroendocrine tumours (G.E.P.N.E.T.). Due to the detection limits of scintigraphy, other metabolic imaging modalities are required. Positron emission topography (PET) offers whole body scanning, facilitates tumour localization, and assesses the metastasis statement of the tumour. {sup 18}F-F.D.G. is the most frequent radiotracer used in clinical practice because of its availability, but its interest is demonstrated only in undifferentiated G.E.P.N.E.T.. More recently, {sup 18}F-DOPA PET showed a high sensitivity in particular in carcinoid tumours detection. PET using different {sup 68}Ga-labeled-somatostatin analogs with high affinity for sst2 displayed better results than somatostatin receptors scintigraphy (S.R.S.) in G.E.P.N.E.T. primary tumour and metastasis detection, especially when fusion with computerized tomography images was performed. Using similar metabolic targets, peptide receptor radionuclide therapy (P.R.R.T.) with {sup 177}Lu-octreotate and {sup 90}Y-DOTA-TOC, is indicated in disseminated G.E.P.N.E.T. forms with an efficiency of 30 % and a minor toxicity. (authors)

  12. Survival prediction in patients undergoing radionuclide therapy based on intratumoral somatostatin-receptor heterogeneity

    Science.gov (United States)

    Ilhan, Harun; Higuchi, Takahiro; Buck, Andreas K.; Lehner, Sebastian; Bartenstein, Peter; Bengel, Frank; Schatka, Imke; Muegge, Dirk O.; Papp, László; Zsótér, Norbert; Große-Ophoff, Tobias; Essler, Markus; Bundschuh, Ralph A.

    2017-01-01

    The NETTER-1 trial demonstrated significantly improved progression-free survival (PFS) for peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors (NET) emphasizing the high demand for response prediction in appropriate candidates. In this multicenter study, we aimed to elucidate the prognostic value of tumor heterogeneity as assessed by somatostatin receptor (SSTR)-PET/CT. 141 patients with SSTR-expressing tumors were analyzed obtaining SSTR-PET/CT before PRRT (1-6 cycles, 177Lu somatostatin analog). Using the Interview Fusion Workstation (Mediso), a total of 872 metastases were manually segmented. Conventional PET parameters as well as textural features representing intratumoral heterogeneity were computed. The prognostic ability for PFS and overall survival (OS) were examined. After performing Cox regression, independent parameters were determined by ROC analysis to obtain cut-off values to be used for Kaplan-Meier analysis. Within follow-up (median, 43.1 months), 75 patients showed disease progression (median, 22.2 m) and 54 patients died (median, 27.6 m). Cox analysis identified 8 statistically independent heterogeneity parameters for time-to-progression and time-to-death. Among them, the textural feature Entropy predicted both PFS and OS. Conventional PET parameters failed in response prediction. Imaging-based heterogeneity assessment provides prognostic information in PRRT candidates and outperformed conventional PET parameters. Its implementation in clinical practice can pave the way for individualized patient management. PMID:27705948

  13. Inhibition of MNK pathways enhances cancer cell response to chemotherapy with temozolomide and targeted radionuclide therapy.

    Science.gov (United States)

    Grzmil, Michal; Seebacher, Jan; Hess, Daniel; Behe, Martin; Schibli, Roger; Moncayo, Gerald; Frank, Stephan; Hemmings, Brian A

    2016-09-01

    Current standard-of-care treatment for malignant cancers includes radiotherapy and adjuvant chemotherapy. Here, we report increased MAP kinase-interacting kinase (MNK)-regulated phosphorylation of translation initiation factor 4E (eIF4E) in glioma cells upon temozolomide (TMZ) treatment and in medullary thyroid carcinoma (MTC) cells in response to targeted radionuclide therapy. Depletion of MNK activity by using two MNK inhibitors, CGP57380 or cercosporamide, as well as by MNK1-specific knockdown sensitized glioblastoma (GBM) cells and GBM-derived spheres to TMZ. Furthermore, CGP57380 treatment enhanced response of MTC cells to (177)Lu-labeled gastrin analogue. In order to understand how MNK signaling pathways support glioma survival we analyzed putative MNK substrates by quantitative phosphoproteomics in normal condition and in the presence of TMZ. We identified MNK inhibitor-sensitive phosphorylation sites on eIF4G1, mutations of which either influenced eIF4E phosphorylation or glioma cell response to TMZ, pointing to altered regulation of translation initiation as a resistance mechanism. Pharmacological inhibition of overexpressed MNK1 by CGP57380 reduced eIF4E phosphorylation and induced association of inactive MNK1 with eIF4G1. Taken together, our data show an activation of MNK-mediated survival mechanisms in response to either glioma chemotherapy or MTC targeted radiation and suggest that inhibition of MNK activity represents an attractive sensitizing strategy for cancer treatments.

  14. The prognostic influence of the proliferative discordance in metastatic pancreatic neuroendocrine carcinoma revealed by peptide receptor radionuclide therapy

    Science.gov (United States)

    Montanier, Nathanaëlle; Joubert-Zakeyh, Juliette; Pétorin, Caroline; Montoriol, Pierre François; Maqdasy, Salwan; Kelly, Antony

    2017-01-01

    Abstract Rationale: Pancreatic neuroendocrine tumors (pNET) are rare slowly growing tumors with a high metastatic potential. Peptide receptor radionuclide therapy (PRRT) with radiolabeled analogues has been developed as a new tool for the management of metastatic well-differentiated (grade 1 and 2) neuroendocrine tumors expressing somatostatin receptor (SSTR2). Chemotherapy is the mainstay in the management of grade 3 (G3) unresectable pancreatic neuroendocrine carcinoma (pNEC). To date, no study has evaluated the efficacy of PRRT in such tumors. Diagnoses and interventions: We describe a case of a progressive G3 pNEC with huge liver metastases successfully treated with PRRT (177Lu DOTATATE). Outcomes: Complete remission was obtained for 3 years. Indeed, the mitotic index was low (as G2 tumors) but with a very high Ki-67 index (45%–70%). Such discordance between the proliferative markers should consider the use of PRRT before chemotherapy in unresectable metastatic G3 tumors expressing SSTR2. Lessons: This case supports the hypotheses highlighting the heterogeneity of G3 pNEC. The latter should be subdivided into 2 distinct categories: proliferation-discordant (well differentiated) and concordant (poorly differentiated) NEC. PRRT could be suggested for the former group before the conventional chemotherapy. PMID:28178157

  15. Development of modern approach to absorbed dose assessment in radionuclide therapy, based on Monte Carlo method simulation of patient scintigraphy

    Science.gov (United States)

    Lysak, Y. V.; Klimanov, V. A.; Narkevich, B. Ya

    2017-01-01

    One of the most difficult problems of modern radionuclide therapy (RNT) is control of the absorbed dose in pathological volume. This research presents new approach based on estimation of radiopharmaceutical (RP) accumulated activity value in tumor volume, based on planar scintigraphic images of the patient and calculated radiation transport using Monte Carlo method, including absorption and scattering in biological tissues of the patient, and elements of gamma camera itself. In our research, to obtain the data, we performed modeling scintigraphy of the vial with administered to the patient activity of RP in gamma camera, the vial was placed at the certain distance from the collimator, and the similar study was performed in identical geometry, with the same values of activity of radiopharmaceuticals in the pathological target in the body of the patient. For correct calculation results, adapted Fisher-Snyder human phantom was simulated in MCNP program. In the context of our technique, calculations were performed for different sizes of pathological targets and various tumors deeps inside patient’s body, using radiopharmaceuticals based on a mixed β-γ-radiating (131I, 177Lu), and clear β- emitting (89Sr, 90Y) therapeutic radionuclides. Presented method can be used for adequate implementing in clinical practice estimation of absorbed doses in the regions of interest on the basis of planar scintigraphy of the patient with sufficient accuracy.

  16. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    Science.gov (United States)

    Costa, Ricardo; Bacchi, Carlos E.; Almeida Filho, Paulo

    2013-01-01

    Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET)/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU). PMID:24455330

  17. VIDA: a voxel-based dosimetry method for targeted radionuclide therapy using Geant4.

    Science.gov (United States)

    Kost, Susan D; Dewaraja, Yuni K; Abramson, Richard G; Stabin, Michael G

    2015-02-01

    We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to provide patient-specific dosimetry in targeted radionuclide therapy performing Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code generates voxel-level dose rate maps using anatomical and physiological data taken from individual patients. Voxel level dose rate curves are then fit and integrated to yield a spatial map of radiation absorbed dose. In this article, we present validation studies using established dosimetry results, including self-dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit density spheres and organ self- and cross-organ DFs in the Radiation Dose Assessment Resource (RADAR) reference adult phantom. The comparison with reference data demonstrated agreement within 5% for self-DFs to spheres and reference phantom source organs for four common radionuclides used in targeted therapy ((131)I, (90)Y, (111)In, (177)Lu). Agreement within 9% was achieved for cross-organ DFs. We also present dose estimates to normal tissues and tumors from studies of two non-Hodgkin Lymphoma patients treated by (131)I radioimmunotherapy, with comparison to results generated independently with another dosimetry code. A relative difference of 12% or less was found between methods for mean absorbed tumor doses accounting for tumor regression.

  18. Dose evaluation of therapeutic radiolabeled bleomycin complexes based on biodistribution data in wild-type rats:Effect of radionuclides in absorbed dose of different organs

    Institute of Scientific and Technical Information of China (English)

    Hassan Yousefnia; Samaneh Zolghadri; Amir Reza Jalilian; Mohammad Ghannadi-Maragheh

    2015-01-01

    Bleomycins (BLMs), as tumor-seeking antibiotics, have been used for over 20 years in treatment of several types of cancers. Several radioisotopes are used in radiolabeling of BLMs for therapeutic and diagnostic purpos-es. An important points in developing new radiopharmaceuticals, especially therapeutic agents, is the absorbed dose delivered in critical organs. In this work, absorbed dose to organs after injection of 153Sm-, 177Lu-and 166Ho-labeled BLM was investigated by radiation dose assessment resource (RADAR) method based on biodis-tribution data in wild-type rats. The absorbed dose effect of the radionuclides was evaluated. The maximum absorbed dose for the complexes was observed in the kidneys, liver and lungs. For all the radiolabeled BLMs, bone and red marrow received considerable absorbed dose. Due to the high energy beta particles emitted by 166Ho, higher absorbed dose is observed for 166Ho-BLM in the most organs. The reported data can be useful for the determination of the maximum permissible injected activity of the radiolabeled BLMs in the treatment planning programs.

  19. Metastatic Insulinoma Managed with Radiolabeled Somatostatin Analog

    Directory of Open Access Journals (Sweden)

    Ricardo Costa

    2013-01-01

    Full Text Available Insulinoma is a rare pancreatic neuroendocrine tumor. Overproduction of insulin and associated hypoglycemia are hallmark features of this disease. Diagnosis can be made through demonstration of hypoglycemia and elevated plasma levels of insulin or C-Peptide. Metastatic disease can be detected through computerized tomography (CT scans, magnetic resonance imaging (MRI, and positron emission tomography (PET/CT. Somatostatin receptor scintigraphy can be used not only to document metastatic disease but also as a predictive marker of the benefit from therapy with radiolabeled somatostatin analog. Unresectable metastatic insulinomas may present as a major therapeutic challenge for the treating physician. When feasible, resection is the mainstay of treatment. Prevention of hypoglycemia is a crucial goal of therapy for unresectable/metastatic tumors. Diazoxide, hydrochlorothiazide, glucagon, and intravenous glucose infusions have been used for glycemic control yielding temporary and inconsistent results. Sandostatin and its long-acting depot forms have occasionally been used in the treatment of Octreoscan-positive insulinomas. Herein, we report a case of metastatic insulinoma with very difficult glycemic control successfully treated with the radiolabeled somatostatin analog lutetium (177LU.

  20. Taxa de filtração glomerular pelo EDTA marcado com 51cromo e com 113míndio em equinos Glomerular fltration rate by 51chomium and 113m indium labeled EDTA in horses

    Directory of Open Access Journals (Sweden)

    C. Maliska

    2009-06-01

    Full Text Available Determinou-se a taxa de filtração glomerular por meio do EDTA, marcado com 51Cr e com 113mIn, pela técnica de injeção única, em nove equinos, seis machos e três fêmeas com idades de dois a 12 anos. A taxa de filtração glomerular foi calculada a partir da curva de desaparecimento no plasma e do volume de distribuição do radiotraçador, 51Cr-EDTA ou 113mIn-EDTA. O resultado (média±desvio-padrão foi de 148,80±26,42mL.min-1.100kg. Conclui-se que a medida da taxa de filtração glomerular pelo 51Cr-EDTA ou 113mIn-EDTA, pela técnica de injeção única, elimina o cateterismo vesical e, por sua simplicidade, comodidade, precisão e baixa dose de radiação, pode ser empregada em cavalos como método de escolha em rotina clínica.The glomerular filtration rate was determined in nine healthy horses, six male and three female, aged two to 12-year-old, by means of 51Cr and 113mIn labeled EDTA single injection technique. The glomerular filtration rate was calculated from the plasma disappearance curve and the volume of distribution of the radiotracer, 51Cr-EDTA or 113mIn-EDTA. The result (mean±standard deviation was 148.80±26.42mL.min-1.100kg. It is concluded that the measurement of glomerular filtration rate by 51Cr-EDTA or 113mIn-EDTA by single injection technique eliminates the bladder catheterization, and for its simplicity, convenience, accuracy, and low dose of radiation, can be used in horses as a method of choice in clinical routine.

  1. Pharmacokinetics of BMEDA after Intravenous Administration in Beagle Dogs

    Directory of Open Access Journals (Sweden)

    Chih-Hsien Chang

    2014-01-01

    Full Text Available The pharmacokinetics of N,N-bis(2-mercapatoethly-N',N'-diethylenediamine (BMEDA, a molecule that can form a chelate with rhenium-188 (188Re to produce the 188Re-BMEDA-liposomes, was studied. In this work, beagles received a single injection of BMEDA, at doses of 1, 2, or 5 mg/kg; the concentration of BMEDA in the beagles’ plasma was then analyzed and determined by liquid chromatography-mass spectrometry/mass spectrometry. Based on the pharmacokinetic parameters of BMEDA, we found that male and female animals shared similar patterns indicating that the pharmacokinetics of BMEDA is independent of gender differences. In addition, the pharmacokinetics of BMEDA was seen to be non-linear because the increase of mean AUC0–t and AUC0–∞ values tend to be greater than dose proportional while the mean Vss and CL values of BMEDA appeared to be dose dependent. The information on the pharmacokinetics of BMEDA generated from this study will serve as a basis to design appropriate pharmacology and toxicology studies for future human use.

  2. Pharmacokinetic properties of new antitumor radiopharmaceutical on the basis of diamond nanoporous composites labeled with rhenium-188

    Science.gov (United States)

    Petriev, V. M.; Tishchenko, V. K.; Kuril’chik, A. A.; Skvortsov, V. G.

    2017-01-01

    Today the development of address therapeutic radionuclide delivery systems directly to tumor tissue is of current interest. It can be achieved by the design of drug containers of specific sizes and shapes from carbon-based composite materials. It will be allowed to enhance the efficacy of anticancer therapy and avoid serious side effects. In this work we studied the pharmacokinetic properties of nanodiamond nanoporous composite labeled with rhenium-188 in rats with hepatocholangioma PC-1 after intratumoral injection. It was established that substantial part of injected radioactivity remained in tumor tissue. Within three hours after 188Re-nanoporous composites injection activity in tumor constituted 79.1–91.3% of injected dose (ID). Then activity level declined to 45.9% ID at 120 hours. No more than 1.34% ID entered the bloodstream. In soft organs and tissues, except thyroid gland, the content of compound didn’t exceed 0.3% ID/g. The highest activity in thyroid gland was 6.95% ID/g. In conclusion, received results suggest 188Re-nanoporous composites can be promising radionuclide delivery systems for cancer treatment.

  3. Radiosynovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Deog Yoon [Kyunghee University School of Medicine, Seoul (Korea, Republic of)

    2006-04-15

    Radiosynovectomy has been used as an effective treatment in patients with resistant synovitis after failure of long-term medication and intraarticular steroid injection. Although {sup 90}Y silicate/citrate, {sup 186}Re sulfide, and {sup 169}Er citrate were approved in Europe for the appropriate radiopharmaceuticals for radiosynovectomy, other radionuclides such as {sup 32}P-chromic phosphate, {sup 165}Dy-ferric hydroxide macroaggregate, {sup 188}Rh-microspheres, {sup 153}Sm-particulate, and {sup 166}Ho- ferric hydroxide macroaggregate have been used in many countries. Reported success rates range from 40% to 90% for the different joints and underlying disease. In Korea, {sup 188}Re-tin-colloid and {sup 166}Ho-chitosan complex are now using as the major radionuclides in radiosynovectomy with good clinical results. A study on radiation synovectomy using {sup 188}Re-tin-colloid for patients with Korean rheumatoid arthritis shows the treatment resulted in the improvement of arthritis and well tolerated. In our study, the radiosynovectomy with {sup 166}Ho- chitosan complex in 53 hemophilic patients markedly decreased intra-articular bleeding frequency and need for coagulation factor. This review includes general principles in the application of radiosynovectomy and the clinical experience in Korea.

  4. Evaluating the potential of a new isotope-labelled glyco-ligand for estimating the remnant liver function of schistosoma-infected mice.

    Science.gov (United States)

    Cheng, P-C; Chiang, P-F; Lee, K-M; Yeh, C-H; Hsu, K-L; Liu, S-W; Shen, L-H; Peng, C-L; Fan, C-K; Luo, T-Y

    2013-01-01

    A new glyco-derivative compound (OCTAM) was developed and labelled with isotope to form (188) Re-OCTAM as a candidate nuclear medicine imaging agent for testing the liver function. We evaluated the potential of isotope-labelled OCTAM for estimating the remnant liver function in vitro and in vivo schistosoma-infected mice. The affinity of OCTAM to liver asialoglycoprotein receptors (ASGPR) was assessed by competitive inhibition assay in vitro. In vivo assessments were performed to score the remnant liver function in mice at different schistosomal infection stages. OCTAM binds specifically to ASGPR and showed competitive inhibition of anti-ASGPR antibody binding to hepatocytes, and was higher than that of other galactosyl ligands. Micro-SPECT/CT images of uninfected mice revealed strong liver uptake. Quantified serial images of mice infected for 9, 12 and 18 weeks showed delayed liver uptake, and the retention of uptake was inversely correlated with stage and grade of schistosoma infection. Pathological and biochemical analysis demonstrated that gradually accumulating liver injury caused by infection significantly influenced uptake of (188) Re-OCTAM. Hepatic ASGPR expression diminished only in the chronic infection stage. This study demonstrated that the isotope-labelled OCTAM could accumulate in the liver, might have potential as an imaging agent for in vivo hepatic function evaluation of schistosomiasis.

  5. Preparation and biodistribution of 186,188Re—HEDP for bone tumor therapy

    Institute of Scientific and Technical Information of China (English)

    罗顺忠; 谯健; 等

    1996-01-01

    Radionuclides186,188Re,suitable for tumor therapy and with high specific activity,are prepared through irradiating natural metallic rhenium,instead of costly enriched target,Complexation of rhenium with HEDP(1-hydroxy ethylidene diphosphonate)is mainly dependent on pH values and the reductant concentrations in the medium,and the yield is not less than 0.95 in pH2.0-4.0 and SnⅡconcentration of 0.012-0.018mol/L.The 186,188ReHEDP complex has high stability in vitro and in vivo in the presence of protecting agent,and gives superior biological properties in small animals,similar to those of 153Sm-EDTMP including faster blood clearance,lower soft tissue residue and higher skeletal uptake with the peak of 0.2576 ID/g at 1h post injection(overseas report 0.0101 ID/g)comparable to that of 153m-EDTMP(0.2644ID/g) at 3h post injection.

  6. MOLECULAR ANALYSIS OF RADIATION-INDUCED MUTATION IN EXON 7/8 OF RAT HPRT GENE

    Institute of Scientific and Technical Information of China (English)

    任晓庆; 黄定九; 黄钢; 王利民

    2003-01-01

    Objective To investigate the relationship between the radiation dose and the HPRT gene locus mutation in rat smooth muscle cells, and provide the molecular basis for prevention of restenosis after percutaneous transluminal coronary angioplasty (PTCA).MethodsThe smooth muscle cells cultured in vitro were irradiated by radionuclide 188Re in different doses. HPRT gene mutation colonies were selected and isolated by 6 thioguanine. Analysis of mutation in exon 7/8 of HPRT gene were accomplished by polymerase chain reaction and single strand conformation polymorphism.ResultsThe HPRT gene mutation frequency of rat smooth muscle cells that were irradiated by radionuclide 188Re ranged from 5.5×10-6 to 13×10-6. Of 91 HPRT gene mutation colonies, 13(14.3%) contained exon 7/8 deletion and 15(16.5%) had point mutation. The exon 7/8 mutation frequency was 30.8%. There were significant relationships between radiation dose and mutation frequency of HPRT gene and exon 7/8.ConclusionThe DNA damage and gene mutation induced by radiation has positive relationship with radiation dose, and is a basis of proliferation inhibition and apoptosis of smooth muscle cells.

  7. Gastroesophageal reflux in children with recurrent abdominal pain.

    Science.gov (United States)

    van der Meer, S B; Forget, P P; Kuijten, R H; Arends, J W

    1992-02-01

    In this study we investigated the presence of gastroesophageal reflux in children with recurrent abdominal pain and its possible relationship to food intolerance-associated duodenal inflammation. Twenty-four-hour intra-esophageal pH monitoring, an endoscopic duodenal biopsy and a small bowel 51Cr-EDTA permeability test were performed in 25 children with recurrent abdominal pain. In 14 cases (56%) the pH monitoring was abnormal, pointing to the presence of pathological gastroesophageal reflux. Treatment of gastroesophageal reflux in the latter patients resulted in resolution or improvement of abdominal pain in 10 cases (71%). Gastroesophageal reflux did not appear to be associated with either intestinal permeability to 51Cr-EDTA or duodenal biopsy findings. We conclude that pathological gastroesophageal reflex is a frequent finding in children with recurrent abdominal pain, that it is unrelated to duodenal inflammation and that there might be a causal relationship between pathological gastroesophageal reflux and recurrent abdominal pain in children.

  8. Måling af nyrefunktion under cytostatisk behandling

    DEFF Research Database (Denmark)

    Hartlev, Louise Brøndt; Bøje, Charlotte Rotbøl; Bluhme, Henrik;

    2008-01-01

    INTRODUCTION: Some cytostatics, used in the treatment of cancer, are excreted by the kidneys and may be nephrotoxic. The glomerular filtration rate (GFR) represents a method for reliable assessement of the 51Cr-EDTA plasma clearance before and during treatment with nephrotoxic drugs. The aim...... of this retrospective study was to evaluate whether this method could be replaced by a more simplified GFR estimate calculated from the creatinine plasma concentration. MATERIALS AND METHODS: We included all patients who had had at least four GFR measurements in 2005 as part of their nephrotoxic cytostatic treatment....... The estimated GFR (eGFR) was calculated from sex, age and weight, according to the Cockcroft formula. RESULTS: Forty-eight patients with a mean age of 47 years were included. 51Cr-EDTA plasma clearance and eGFR showed a poor correlation (r(2) = 0,678). On average, GFR decreased from 95 ml/min to 80 ml/min from...

  9. Chromium and vanadium effects on glucose and lipid metabolism of guinea pigs and obese and diabetic mice

    Energy Technology Data Exchange (ETDEWEB)

    Li, Y.C.

    1987-01-01

    Severe chromium deficiency in experimental animals may contribute to insulin resistance, impaired glucose tolerance and elevated serum cholesterol concentration. Vanadium also has been reported to be a nutritionally important element for both chicks and rats, but its function and even its essentiality are still in question. Chromium absorption even from supplemented diets is poor, thus efforts were made to study the site of absorption of /sup 51/Cr from CrCl/sub 3/. /sup 51/Cr was found to move very rapidly through the GI tract and appears to flow with dietary and secreted water. It was not absorbed from the stomach. In a study with guinea pigs, vanadate supplementation appeared to affect cholesterol fraction. Chromium supplementation lowered serum triacylglycerol concentrations at the end of an 18-week study. Since the previous study and others have indicated a role for chromium and vanadium in lipid carbohydrate metabolism, experiments were designed to compare effects of chromium and vanadium supplements on related parameters.

  10. Estimation of Glomerular Filtration Rate in Elderly Chronic Kidney Disease Patients: Comparison of Three Novel Sophisticated Equations and Simple Cystatin C Equation.

    Science.gov (United States)

    Bevc, Sebastjan; Hojs, Nina; Hojs, Radovan; Ekart, Robert; Gorenjak, Maksimiljan; Puklavec, Ludvik

    2017-04-01

    Estimating glomerular filtration rate (GFR) in elderly patients is a problem, since they are poorly represented in studies developing GFR equations. Serum cystatin C is a better indicator of GFR than serum creatinine in elderly patients. Therefore the aim of our study was to compare frequently used serum cystatin C based GFR equations with a gold standard ((51) CrEDTA clearance) in elderly chronic kidney disease (CKD) patients. 106 adult Caucasian patients, older than 65 years (58 women, 48 men; mean age 72.5 years), were included. In each patient (51) CrEDTA clearance, serum creatinine (IDMS traceable method) and serum cystatin C (immunonephelometric method) were determined. GFR was estimated using the Simple cystatin C, CKD-EPI cystatin C, CKD-EPI creatinine-cystatin C and BIS2 equation. Mean serum creatinine of our patients was 141.4 ± 41.5 μmol/L, mean serum cystatin C 1.79 ± 0.6 mg/L, mean (51) CrEDTA clearance was 52.2 ± 15.9 mL/min per 1.73 m(2) . Statistically significant correlations between (51) CrEDTA clearance and all formulas were found (P C and BIS2 equation underestimated and CKD-EPI cystatin C and Simple cystatin C equation overestimated measured GFR. All equations lacked precision. Analysis of ability to correctly predict patient's GFR below or above 45 mL/min per 1.73 m(2) showed similar ability for all equations (P = 0.24-0.89). All equations are equally accurate for estimating GFR in elderly Caucasian CKD patients. For daily practice Simple cystatin C equation is most practical.

  11. Erythrocyte survival in chronic renal failure. Role of secondary hyperparathyroidism.

    OpenAIRE

    Akmal, M; Telfer, N; Ansari, A N; Massry, S G

    1985-01-01

    The human erythrocyte (RBC) is a target organ for parathyroid hormone (PTH) and the hormone increases RBC osmotic fragility and induces their hemolysis. The present study was undertaken to examine whether elevated blood levels of PTH affect RBC survival, and therefore whether PTH, being an extracorpuscular factor, is responsible for the shortened RBC survival in chronic renal failure. 51Cr-labeled RBC survival was elevated in six normal dogs, in six animals with chronic renal failure and seco...

  12. Results of the whole GALLEX experiment

    Energy Technology Data Exchange (ETDEWEB)

    Cribier, M. [CEA-Saclay, Gif-sur-Yvette (France)

    1998-01-01

    After 5.5 years of data taking, GALLEX ended its experimental phase. The solar neutrino production rate, 76.4 {+-} 8 SNU represents about 55% of the predicted rate. The As tests prove, at the 1% level, the reliability of the technique and the detection of {sup 51}Cr neutrino, with the nominal efficiency (93.0 {+-} 8%), control the response of the detector to neutrinos in the solar energy range.

  13. Chromium 51-ethylenediaminetetraacetate test: a useful test in the assessment of inflammatory bowel disease

    Energy Technology Data Exchange (ETDEWEB)

    O' Morain, C.A.; Abelow, A.C.; Chervu, L.R.; Fleischner, G.M.; Das, K.M.

    1986-11-01

    We evaluated the usefulness of urinary excretion values in assessing mucosal damage in inflammatory bowel disease after administration of chromium 51-labeled EDTA either orally or rectally. In the oral study, 19 controls, 18 patients with Crohn's disease, and 13 patients with ulcerative colitis were given 100 microCi /sup 51/Cr-EDTA by mouth. The amount of /sup 51/Cr-EDTA in a 24-hour urine collection was expressed as a percentage of the ingested dose. The patients with Crohn's disease of the small bowel excreted 6.3% +/- 4.3%, which was significantly (P less than 0.001) higher than the percentage in patients with ulcerative colitis (1.7% +/- 1.1%) and controls (1.4% +/- 0.6%). In the enema study, 19 patients with ulcerative colitis, two with Crohn's disease, two with radiation colitis, and four controls (spastic colitis, lactose intolerance) were given 100 microCi /sup 51/Cr-EDTA by retention enema. The patients with active colonic inflammation excreted 8.4% +/- 3.9% of the dose given by enema, which was significantly (P less than 0.01) higher than in other controls (1.9% +/- 0.91%) or patients with inactive colitis (2.2% +/- 1.9%). The /sup 51/Cr-EDTA excretion test is a safe, inexpensive test useful in evaluating patients with inflammatory bowel disease. It can be given orally to screen patients with abdominal complaints who are suspected of having Crohn's disease involving the small intestine, and when given by enema it provides additional objective assessment of idiopathic ulcerative colitis or proctitis.

  14. Neutrophil-induced injury of rat pulmonary alveolar epithelial cells.

    OpenAIRE

    Simon, R H; DeHart, P D; Todd, R F

    1986-01-01

    The damage to pulmonary alveolar epithelial cells that occurs in many inflammatory conditions is thought to be caused in part by phagocytic neutrophils. To investigate this process, we exposed monolayers of purified rat alveolar epithelial cells to stimulated human neutrophils and measured cytotoxicity using a 51Cr-release assay. We found that stimulated neutrophils killed epithelial cells by a process that did not require neutrophil-generated reactive oxygen metabolites. Pretreatment of neut...

  15. Escaping the correction for body surface area when calculating glomerular filtration rate in children

    Energy Technology Data Exchange (ETDEWEB)

    Piepsz, Amy; Tondeur, Marianne [CHU St. Pierre, Department of Radioisotopes, Brussels (Belgium); Ham, Hamphrey [University Hospital Ghent, Department of Nuclear Medicine, Ghent (Belgium)

    2008-09-15

    {sup 51}Cr ethylene diamine tetraacetic acid ({sup 51}Cr EDTA) clearance is nowadays considered as an accurate and reproducible method for measuring glomerular filtration rate (GFR) in children. Normal values in function of age, corrected for body surface area, have been recently updated. However, much criticism has been expressed about the validity of body surface area correction. The aim of the present paper was to present the normal GFR values, not corrected for body surface area, with the associated percentile curves. For that purpose, the same patients as in the previous paper were selected, namely those with no recent urinary tract infection, having a normal left to right {sup 99m}Tc MAG3 uptake ratio and a normal kidney morphology on the early parenchymal images. A single blood sample method was used for {sup 51}Cr EDTA clearance measurement. Clearance values, not corrected for body surface area, increased progressively up to the adolescence. The percentile curves were determined and allow, for a single patient, to estimate accurately the level of non-corrected clearance and the evolution with time, whatever the age. (orig.)

  16. Role of mucus in gastric mucosal injury induced by local ischemia/reperfusion.

    Science.gov (United States)

    Seno, K; Joh, T; Yokoyama, Y; Itoh, M

    1995-09-01

    The role of gastric mucus was evaluated in a rat model of gastric epithelial damage induced by local ischemia/reperfusion (I/R) stress. In this model, blood-to-lumen chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) clearance served as an index of injury. Tetraprenyl acetone (TPA; 100 mg, 200 mg/kg IP) was used to stimulate mucus production. Administration of TPA increased both the hexosamine content in gastric tissue and the amount of alcian blue-periodic acid Schiff (AB-PAS) stained mucus in the mucosa in a dose-dependent manner. Increases in 51Cr-EDTA clearance induced by I/R were significantly attenuated by TPA in a dose-dependent manner. N-acetyl-L-cysteine (NAC; 0.6%, 0.8%) was perfused into the gastric lumen to assess the effect of reduction in mucus on the injury induced by I/R. Although mean values of hexosamine content were increased by perfusion with NAC, AB-PAS-stained mucus in the mucosa was significantly decreased in a dose-dependent manner. Perfusion of NAC did not change basal 51Cr-EDTA clearance but significantly exacerbated the increase in clearance induced by I/R in a dose-dependent manner. These results indicate that gastric mucus protects the gastric mucosa against I/R stress in vivo.

  17. Method for the quantitation of gastric emptying time of gel test meals.

    Science.gov (United States)

    Russell, J; Bass, P

    1984-09-01

    Isotopic markers were developed to allow measurement of the gastric emptying times of homogeneous and nonhomogeneous gel meals. Meals containing the dietary fibers psyllium and guar gum presented as homogeneous, viscous gels while meals containing the synthetic polymer polycarbophil presented as discrete gel particle-water mixtures. Fiber meals were labeled differently than polycarbophil meals. Fiber meals were labeled with 51Cr-CM-Sephadex. The marker was uniformly suspended in meals containing at least 1% guar or 2% psyllium. In contrast, polycarbophil particles were labeled by hydrating the dried granules with saline in which Na2(51)CrO4 had been dissolved. Use of the markers to measure gastric emptying was demonstrated in dogs fitted with duodenal cannulas. Half of the fiber meals emptied from the stomach in about 40 min without significant dilution by secretions. In contrast, only 8% of the polycarbophil particles emptied by 90 min. Particle-specific labeling of polycarbophil was important because the meal effluent was diluted extensively by secretions. We conclude that 51Cr-CM-Sephadex and soluble Cr-51 may be used as meal markers for estimation of the gastric emptying times of certain homogeneous and nonhomogeneous gel-type meals, respectively.

  18. Measuring melanoma-specific cytotoxic T lymphocytes elicited by dendritic cell vaccines with a tumor inhibition assay in vitro.

    Science.gov (United States)

    Paczesny, Sophie; Shi, Honhgzhen; Saito, Hiroaki; Mannoni, Patrice; Fay, Joseph; Banchereau, Jacques; Palucka, A Karolina

    2005-01-01

    Improving cancer vaccines depends on assays measuring elicited tumor-specific T-cell immunity. Cytotoxic effector cells are essential for tumor clearance and are commonly evaluated using 51Cr release from labeled target cells after a short (4 hours) incubation with T cells. The authors used a tumor inhibition assay (TIA) that assesses the capacity of cytotoxic T lymphocytes (CTLs) to control the survival/growth of EGFP-labeled tumor cell lines. TIA was validated using CD8+ T cells primed in vitro against melanoma and breast cancer cells. TIA was then used to assess the CTL function of cultured CD8+ T cells isolated from patients with metastatic melanoma who underwent vaccination with peptide-pulsed CD34+ HPCs-derived DCs. After the DC vaccination, T cells from six of eight patients yielded CTLs that could inhibit the survival/growth of melanoma cells. The results of TIA correlated with killing of tumor cells in a standard 4-hour 51Cr release assay, yet TIA allowed detection of CTL activities that appeared marginal in the 51Cr release assay. Thus, TIA might prove valuable for measuring spontaneous and induced antigen-specific cytotoxic T cells.

  19. Beta-2-microglobulin excretion: an indicator of long term nephrotoxicity during cis-platinum treatment?

    DEFF Research Database (Denmark)

    Sørensen, P G; Nissen, Mogens Holst; Groth, S;

    1985-01-01

    To evaluate the value of beta-2-microglobulin as an indicator of acute and long-term cis-platinum-induced nephrotoxicity, 51Cr-EDTA clearance and serum concentration and urinary excretion of beta-2-microglobulin were measured in 18 patients treated with a regimen including cis-platinum. Before...... treatment all values were within the normal range. During treatment 51Cr-EDTA clearance decreased from 108 to 90 ml/min/1.73 m2 (P less than 0.02). The decrease was irreversible, while a transient 2 to 5-fold increase in beta-2-microglobulin excretion in the urine was seen during treatment. Serum beta-2......-microglobulin remained unchanged. The decrease in 51Cr-EDTA clearance was not correlated to either the peak increase in the beta-2-microglobulin excretion or to the time of occurrence of the peak (R = 0.3). Thus, it is not possible to predict the long-term nephrotoxicity of cis-platinum by measuring the beta-2...

  20. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A. [Ulm Univ. (Germany). Abt. Nuklearmedizin; Bunjes, D.; Doehner, H. [Abteilung Innere Medizin III, Haematologie und Onkologie, Universitaetsklinikum Ulm (Germany); Martin, H.; Bergmann, L. [Klinik fuer Haematologie und Onkologie, Johann-Wolfgang-Goethe Universitaet Frankfurt (Germany)

    2001-07-01

    Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ({sup 188}Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2{+-}2.1 (range 6.9-15.8) GBq {sup 188}Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4{+-}5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking {sup 188}Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

  1. Biokinetics and dosimetry of target-specific radiopharmaceuticals for molecular imaging and therapy

    Energy Technology Data Exchange (ETDEWEB)

    Ferro F, G.; Torres G, E. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico); Gonzalez V, A. [UAEM, Facultad de Medicina, Toluca (Mexico); Murphy, C.A. de [INCMNSZ, Mexico D.F. (Mexico)

    2006-07-01

    Molecular imaging techniques directly or indirectly monitor and record the spatiotemporal distribution of molecular or cellular processes for biochemical, biologic, diagnostic or therapeutic applications. {sup 99m}Tc-HYNlC-TOC has shown high in vitro and in vivo stability, rapid background clearance and rapid detection of somatostatin receptor-positive tumors. Therapies using radiolabeled anti-CD20 have demonstrated their efficacy in patients with B-cell non Hodgkin's Iymphoma (NHL). The aim of this study was to establish biokinetic models for {sup 99m}Tc-HYNlC-TOC and {sup 188}Re-anti-CD20 prepared from Iyophilized kits, and to evaluate their dosimetry as target-specific radiopharmaceuticals. Whole-body images were acquired at different times after {sup 99m}Tc-HYNlC-TOC or {sup 188}Re-anti-CD20 administration obtained from instant freeze-dried kit formulations with radiochemical purities > 95 %. Regions of interest (ROls) were drawn around source organs on each time frame. The cpm of each ROI was converted to activity using the conjugate view counting method. The image sequence was used to extrapolate time-activity curves in each organ, to adjust the biokinetic model using the SAAM software, and to calculate the total number of disintegrations (N) that occurred in the source regions. N data were the input for the OLINDA/EXM code to calculate internal radiation dose estimates. {sup 99m}Tc-HYNlC-TOC images showed an average tumor/blood (heart) ratio of 4.3 {+-} 0.7 in receptor-positive tumors at 1 h and the mean radiation absorbed dose calculated for a study using 740 MBq was 24, 21.5, 5.5 and 1.0 mSv for spleen, kidneys, liver and bone marrow respectively and the effective dose was 4.4 mSv. Results showed that after administration of 7 GBq of {sup 188}Re-anti-CD20 the absorbed dose to whole body would be 0.7 Gy (0.1 mGy/MBq) which is the indicated dose for non Hodgkin's Iymphome therapies. (Author)

  2. Urinary recovery of orally administered chromium 51-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in healthy adult male Beagles.

    Science.gov (United States)

    Frias, Rafael; Steiner, Jörg M; Williams, David A; Sankari, Satu; Westermarck, Elias

    2012-05-01

    Objective-To provide values for gastrointestinal permeability and absorptive function tests (GIPFTs) with chromium 51 ((51)Cr)-labeled EDTA, lactulose, rhamnose, d-xylose, 3-O-methyl-d-glucose, and sucrose in Beagles and to evaluate potential correlations between markers. Animals-19 healthy adult male Beagles. Procedures-A test solution containing 3.7 MBq of (51)Cr-labeled EDTA, 2 g of lactulose, 2 g of rhamnose, 2 g of d-xylose, 1 g of 3-O-methyl-d-glucose, and 8 g of sucrose was administered intragastrically to each dog. Urinary recovery of each probe was determined 6 hours after administration. Results-Mean ± SD (range) percentage urinary recovery was 6.3 ± 1.6% (4.3% to 9.7%) for (51)Cr-labeled EDTA, 3.3 ± 1.1% (1.7% to 5.3%) for lactulose, 25.5 ± 5.0% (16.7% to 36.9%) for rhamnose, and 58.8% ± 11.0% (40.1% to 87.8%) for 3-O-methyl-d-glucose. Mean (range) recovery ratio was 0.25 ± 0.06 (0.17 to 0.37) for (51)Cr-labeled EDTA to rhamnose, 0.13 ± 0.04 (0.08 to 0.23) for lactulose to rhamnose, and 0.73 ± 0.09 (0.60 to 0.90) for d-xylose to 3-O-methyl-d-glucose. Median (range) percentage urinary recovery was 40.3% (31.6% to 62.7%) for d-xylose and 0% (0% to 0.8%) for sucrose. Conclusions and Clinical Relevance-Reference values in healthy adult male Beagles for 6 of the most commonly used GIPFT markers were determined. The correlation between results for (51)Cr-labeled EDTA and lactulose was not as prominent as that reported for humans and cats; thus, investigators should be cautious in the use and interpretation of GIPFTs performed with sugar probes in dogs with suspected intestinal dysbiosis.

  3. Radiolabelled peptides for tumour therapy: current status and future directions. Plenary lecture at the EANM 2002

    Energy Technology Data Exchange (ETDEWEB)

    Jong, Marion de; Kwekkeboom, Dik; Valkema, Roelf; Krenning, Eric P. [Department of Nuclear Medicine, L2, Erasmus MC, 3015 GD, Rotterdam (Netherlands)

    2003-03-01

    On their plasma membranes, cells express receptor proteins with high affinity for regulatory peptides, such as somatostatin. Changes in the density of these receptors during disease, e.g. overexpression in many tumours, provide the basis for new imaging methods. The first peptide analogues successfully applied for visualisation of receptor-positive tumours were radiolabelled somatostatin analogues. The next step was to label these analogues with therapeutic radionuclides for peptide receptor radionuclide therapy (PRRT). Results from preclinical and clinical multicentre studies have already shown an effective therapeutic response when using radiolabelled somatostatin analogues to treat receptor-positive tumours. Infusion of positively charged amino acids reduces kidney uptake, enlarging the therapeutic window. For PRRT of CCK-B receptor-positive tumours, such as medullary thyroid carcinoma, radiolabelled minigastrin analogues are currently being successfully applied. The combination of different therapy modalities holds interest as a means of improving the clinical therapeutic effects of radiolabelled peptides. The combination of different radionuclides, such as {sup 177}Lu- and {sup 90}Y-labelled somatostatin analogues, to reach a wider tumour region of high curability, has been described. A variety of other peptide-based radioligands, such as bombesin and NPY(Y{sub 1}) analogues, receptors for which are expressed on common cancers such as prostate and breast cancer, are currently under development and in different phases of (pre)clinical investigation. Multi-receptor tumour targeting using the combination of bombesin and NPY(Y{sub 1}) analogues is promising for scintigraphy and PRRT of breast carcinomas and their lymph node metastases. (orig.)

  4. Radiolabelled somatostatin analogue treatment in gastroenteropancreatic neuroendocrine tumours: factors associated with response and suggestions for therapeutic sequence

    Energy Technology Data Exchange (ETDEWEB)

    Campana, Davide; Nori, Francesca; Cacciari, Giulia; Tomassetti, Paola [University of Bologna, Department of Medical and Surgical Sciences, Bologna (Italy); Capurso, Gabriele; Panzuto, Francesco; Delle Fave, Gianfranco [University of Rome, Digestive and Liver Disease Unit, Rome (Italy); Partelli, Stefano [Sacro Cuore Don Calabria Hospital, Department of Surgery, Negrar (Italy); University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy); Tamburrino, Domenico; Falconi, Massimo [University of Verona, Department of Surgery, Verona (Italy); Universita Politecnica delle Marche, Pancreas Surgical Unit, Ancona (Italy)

    2013-08-15

    Peptide receptor radionuclide therapy (PRRT) is a relatively new treatment modality for patients with unresectable or metastatic gastroenteropancreatic neuroendocrine tumours (GEP NETs). The aim of this study was to determine the time to progression of patients treated with PRRT and to identify the prognostic factors related to treatment response. Patients with sporadic GEP NETs prospectively treated with PRRT were retrospectively analysed. The primary end point was progression-free survival (PFS). A total of 69 patients (37 men and 32 women; 45 with pancreatic and 24 with gastrointestinal lesion; 22 NET G1 and 41 NET G2) were treated with {sup 90}Y or {sup 177}Lu. The objective response rate was 27.5 % (partial response, PR), while 50.7 % had stable disease and 23.2 % had progressive disease. Significant differences in PFS were observed in relationship to the stage of the disease (44 months for stage III, 23 months for stage IV), the evidence of a PR 6 months after the end of the PRRT (39 months in patients with a PR, 22 months in patients without a PR) and previous transarterial chemoembolization (TACE, yes 13 months vs no 31 months). Stage IV, NET G2 and previous TACE were found to be significant factors for tumour progression at multivariate analysis. Low tumour burden and a low proliferation index represent independent prognostic factors for long PFS, while previous chemoembolization techniques represent independent prognostic factors for early tumour progression and shorter PFS. Our data suggest that chemoembolization techniques to reduce the hepatic tumour burden should be avoided. (orig.)

  5. Modular syntheses of H₄octapa and H₂dedpa, and yttrium coordination chemistry relevant to ⁸⁶Y/⁹⁰Y radiopharmaceuticals.

    Science.gov (United States)

    Price, Eric W; Cawthray, Jacqueline F; Adam, Michael J; Orvig, Chris

    2014-05-21

    The ligands H2dedpa, H4octapa, p-SCN-Bn-H2dedpa, and p-SCN-Bn-H4octapa were synthesized using a new protection chemistry approach, with labile tert-butyl esters replacing the previously used methyl esters as protecting groups for picolinic acid moieties. Additionally, the ligands H2dedpa and p-SCN-Bn-H2dedpa were synthesized using nosyl protection chemistry for the first time. The use of tert-butyl esters allows for deprotection at room temperature in trifluoroacetic acid (TFA), which compares favorably to the harsh conditions of refluxing HCl (6 M) or LiOH that were previously required for methyl ester cleavage. H4octapa has recently been shown to be a very promising (111)In and (177)Lu ligand for radiopharmaceutical applications; therefore, coordination chemistry studies with Y(3+) are described to assess its potential for use with (86)Y/(90)Y. The solution chemistry of H4octapa with Y(3+) is shown to be suitable via solution NMR studies of the [Y(octapa)](-) complex and density functional theory (DFT) calculations of the predicted structure, suggesting properties similar to those of the analogous In(3+) and Lu(3+) complexes. The molecular electrostatic potential (MEP) was mapped onto the molecular surface of the DFT-calculated coordination structures, suggesting very similar and even charge distributions between both the Lu(3+) and Y(3+) complexes of octapa(4-), and coordinate structures between 8 (ligand only) and 9 (ligand and one H2O). Potentiometric titrations determined H4octapa to have a formation constant (log K(ML)) with Y(3+) of 18.3 ± 0.1, revealing high thermodynamic stability. This preliminary work suggests that H4octapa may be a competent ligand for future (86)Y/(90)Y radiopharmaceutical applications.

  6. SU-E-T-154: Calculation of Tissue Dose Point Kernels Using GATE Monte Carlo Simulation Toolkit to Compare with Water Dose Point Kernel

    Energy Technology Data Exchange (ETDEWEB)

    Khazaee, M [shahid beheshti university, Tehran, Tehran (Iran, Islamic Republic of); Asl, A Kamali [Shahid Beheshti University, Tehran, Iran., Tehran, Tehran (Iran, Islamic Republic of); Geramifar, P [Shariati Hospital, Tehran, Iran., Tehran, Tehran (Iran, Islamic Republic of)

    2015-06-15

    Purpose: the objective of this study was to assess utilizing water dose point kernel (DPK)instead of tissue dose point kernels in convolution algorithms.to the best of our knowledge, in providing 3D distribution of absorbed dose from a 3D distribution of the activity, the human body is considered equivalent to water. as a Result tissue variations are not considered in patient specific dosimetry. Methods: In this study Gate v7.0 was used to calculate tissue dose point kernel. the beta emitter radionuclides which have taken into consideration in this simulation include Y-90, Lu-177 and P-32 which are commonly used in nuclear medicine. the comparison has been performed for dose point kernels of adipose, bone, breast, heart, intestine, kidney, liver, lung and spleen versus water dose point kernel. Results: In order to validate the simulation the Result of 90Y DPK in water were compared with published results of Papadimitroulas et al (Med. Phys., 2012). The results represented that the mean differences between water DPK and other soft tissues DPKs range between 0.6 % and 1.96% for 90Y, except for lung and bone, where the observed discrepancies are 6.3% and 12.19% respectively. The range of DPK difference for 32P is between 1.74% for breast and 18.85% for bone. For 177Lu, the highest difference belongs to bone which is equal to 16.91%. For other soft tissues the least discrepancy is observed in kidney with 1.68%. Conclusion: In all tissues except for lung and bone, the results of GATE for dose point kernel were comparable to water dose point kernel which demonstrates the appropriateness of applying water dose point kernel instead of soft tissues in the field of nuclear medicine.

  7. Molecular Imaging of Urogenital Diseases

    Science.gov (United States)

    Cho, Steve Y.; Szabo, Zsolt; Morgan, Russell H.

    2013-01-01

    There is an expanding and exciting repertoire of PET imaging radiotracers for urogenital diseases, particularly in prostate cancer, renal cell cancer, and renal function. Prostate cancer is the most commonly diagnosed cancer in men. With growing therapeutics options for the treatment of metastatic and advanced prostate cancer, improved functional imaging of prostate cancer beyond the limitations of conventional computed tomography (CT) and bone scan (BS) is becoming increasingly important for both clinical management and drug development. PET radiotracers beyond 18F-Fluorodeoxyglucose (FDG) for prostate cancer include 18F-Sodium Fluoride, 11C-Choline and 18F-Fluorocholine and 11C-Acetate. Other emerging and promising PET radiotracers include a synthetic L-leucine amino acid analog (anti-18F-FACBC), dihydrotestosterone analog (18F-FDHT) and prostate specific membrane antigen (PSMA) based PET radiotracers (ex. 18F-DCFBC, 89Zr-DFO-J591, 68Ga(HBED-CC)). Larger prospective and comparison trials of these PET radiotracers are needed to establish the role of PET/CT in prostate cancer. Renal cell cancer imaging with FDG PET/CT although available can be limited, especially for detection of the primary tumor. Improved renal cell cancer detection with carbonic anhydrase IX (CAIX) based antibody (124I-girentuximab) and radioimmunotherapy targeting with 177Lu-cG250 appear promising. Evaluation of renal injury by imaging renal perfusion and function with novel PET radiotracers include p-18F-fluorohippurate (18F-PFH) and hippurate m-cyano-p-18F-fluorohippurate (18F-CNPFH) and Rubidium-82 chloride (typically used for myocardial perfusion imaging). Renal receptor imaging of the renal renin angiotensin system with a variety of selective PET radioligands are also becoming available for clinical translation. PMID:24484747

  8. Kinetics model for lutate dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Lima, M.F.; Mesquita, C.H., E-mail: mflima@ipen.br, E-mail: chmesqui@ipen.br [Instituto de Pesquisas Energeticas (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2013-11-01

    The use of compartmental analysis to predict the behavior of drugs in the organism is considered the better option among numerous methods employed in pharmacodynamics. A six compartments model was developed to determinate the kinetic constants of 177Lu-DOTATATO biodistribution using data from one published study with 67 patients treated by PRRT (Peptide receptor radionuclide therapy) and followed by CT during 68,25 hours. The compartmental analysis was made using the software AnaComp Registered-Sign . The influence of the time pos-injection over the dose assessment was studied taking into account the renal excretion management by aminoacid coinfusion, whose direct effects persist in the first day. The biodistribution curve was split in five sectors: 0-0.25h; 0-3.25h; 3.25-24.25h; 24.25-68.25h and 3.25-68.25h. After the examination of that influence, the study was concentrated in separate the biodistribution curve in two phases. Phase 1: governed by uptake from the blood, considering the time pos-injection until 3.25h and phase 2: governed by renal excretion, considering the time pos-injection from 3.25h to 68.25h. The model considered the organs and tissues superposition in the CT image acquisition by sampling parameters as the contribution of the the activity concentration in blood and relation between the sizes of the whole body and measured organs. The kinetic constants obtained from each phase (1 and 2) were used in dose assessment to patients in 26 organs and tissues described by MIRD. Dosimetry results were in agreement with the available results from literature, restrict to whole body, kidneys, bone marrow, spleen and liver. The advantage of the proposed model is the compartmental method quickness and power to estimate dose in organs and tissues, including tumor that, in the most part, were not discriminate by voxels of phantoms built using CT images. (author)

  9. Peptide receptor chemoradionuclide therapy in small cell carcinoma: from bench to bedside

    Energy Technology Data Exchange (ETDEWEB)

    Lewin, Jeremy; Rao, Aparna; Mileshkin, Linda [Division of Hematology and Medical Oncology, East Melbourne, VIC (Australia); Cullinane, Carleen [Division of Cancer Research, East Melbourne, VIC (Australia); The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC (Australia); Akhurst, Tim; Eu, Peter [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Waldeck, Kelly [Division of Cancer Research, East Melbourne, VIC (Australia); Watkins, D.N. [Monash University, Monash Institute of Medical Research, Clayton, VIC (Australia); Hicks, Rodney J. [Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The University of Melbourne, Sir Peter MacCallum Department of Oncology, Melbourne, VIC (Australia)

    2015-01-15

    Small cell cancers (SmCC), whether pulmonary (SCLC) or extrapulmonary, have a poor prognosis unless localised at diagnosis. Given a proportion of these cancers express somatostatin receptor subtype 2 (SSTR2), we aimed to investigate the efficacy of targeted peptide receptor chemoradionuclide therapy (PRCRT). In this preclinical study, we used a SCLC xenograft mouse model with high expression of SSTR2 to investigate the effect of peptide receptor radionuclide therapy (PRRT) with chemotherapy compared to either alone. We subsequently explored the clinical utility in a patient with SmCC with high SSTR expression treated with PRCRT. Robust expression of SSTR2 in NCI-H69 SCLC xenografts was documented by {sup 68}Ga-DOTA-octreotate (GaTate) (tumour to background uptake ratio = 35). The combination of PRRT using {sup 177}Lu-DOTA-octreotate (LuTate) with carboplatin/etoposide (C/E) chemotherapy was more effective than either LuTate or C/E alone for regression of the NCI-H69 model (p value < 0.05). PRCRT was associated with significantly prolonged survival versus PRRT (p value = 0.0001) or chemotherapy alone (p value = 0.0058). In the subsequent case study, a patient with relapsed SmCC with high SSTR2 expression on GaTate PET underwent PRCRT with radiosensitising etoposide with evidence of a complete metabolic response for 4 months. Given the limited treatment options in this setting, PRCRT is a promising therapeutic option for SSTR2-expressing SmCC. (orig.)

  10. Nuclear oncology, a fast growing field of nuclear medicine

    Science.gov (United States)

    Olivier, Pierre

    2004-07-01

    Nuclear Medicine in oncology has been for a long time synonymous with bone scintigraphy, the first ever whole body imaging modality, and with treatment of thyroid cancer with iodine-131. More recently, somatostatin receptor scintigraphy (SRS) using peptides such as 111In-labelled octreotide became a reference imaging method in the detection and staging of neuroendocrine tumors while 131I- and 123I-MIBG remain the tracers of reference for pheochromocytomas and neuroblastomas. Lymphoscintigraphic imaging based on peritumoral injection of 99mTc-labelled colloids supports, in combination with per operative detection, the procedure of sentinel node identification in breast cancers and melanomas. Positron Emission Tomography (PET) is currently experiencing a considerable growth in oncology based on the use of 18F-FDG (fluorodeoxyglucose), a very sensitive, although non-specific, tumor tracer. Development of instrumentation is crucial in this expansion of PET imaging with new crystals being more sensitive and hybrid imagers that permit to reduce the acquisition time and offer fused PET-CT images. Current developments in therapy can be classified into three categories. Radioimmunotherapy (RIT) based on monoclonal antibodies (or fragments) labelled with beta-emitters. This technique has recently made its entrance in clinical practice with a 90Y-labelled anti-CD20 antibody ( 90Y-ibritumomab tiuxetan (Zevalin ®)) approved in US for the treatment of some subtypes of non-Hodgkin's lymphoma. Radionuclide-bone pain palliation has experienced developments with 153Sm-EDTMP, 186Re-HEDP or 89Sr, efficient in patients with widespread disease. Last, the same peptides, as those used in SRS, are being developed for therapy, labelled with 90Y, 111In or 177Lu in patients who failed to respond to other treatments. Overall, nuclear oncology is currently a fast growing field thanks to the combined developments of radiopharmaceuticals and instrumentation.

  11. Synthesis and evaluation of ligand targeting the somatostatin receptor for drug delivery to tumor cell

    Energy Technology Data Exchange (ETDEWEB)

    Lee, So Young; Hong, Young Don; Jung, Sung Hee; Choi, Sun Ju [Radioisotope Research Division, Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2015-12-15

    Most of targeted therapies block the action of certain enzymes, proteins, or other molecules involved in the growth and spread of cancer cells to produce its cytotoxic effect. Either small molecule drugs or monoclonal antibodies are mostly used in targeted therapies. Unfortunately, targeted therapy has a certain degree of unwanted side effect like other cytotoxicity inducing chemotherapies. To overcome and to reduce unwanted side effects during a cancer therapy, recently radiopeptide therapies has got the worlds' attraction for the tumor targeting modalities due to its beneficial effect on less side effect compared to cytotoxic chemotherapies. Among radiopeptide therapies, {sup 177}Lu-DOTATATE is a major modality as an effective one invented so far in treating neuroendocrine tumor (NET) and it has been in clinical trials at least one decade. Although it does have rather effective therapeutic effect on NET, it has less effective in rather large solid tumor. There are many ways to improve or increase therapeutic effect of radiopeptide are a finding the potent small molecules to target the tumor site selectively, or a labeling with radioisotope of emitting high energy, or an improving its biological half-life by introducing different moieties to increase lipophilicity. Present study was focus to increase a biological halflife of radio somatostatin which will target the somatostatin receptor by altering the bifunctional chelator (BFCA) by introducing lipophilic moiety to the somatostatin, which would make the labeled peptide stay longer in the tumor site and thus it can intensify the therapeutic effect on tumor cell itself and around tissues.

  12. Development of [{sup 90}Y]DOTA-conjugated bisphosphonate for treatment of painful bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Kazuma [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan)], E-mail: kogawa@med.kanazawa-u.ac.jp; Kawashima, Hidekazu [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Shiba, Kazuhiro [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Washiyama, Kohshin; Yoshimoto, Mitsuyoshi [Division of Health Sciences, Graduate School of Medical Science, Kanazawa University, Kanazawa 920-0942 (Japan); Kiyono, Yasushi [Biomedical Imaging Research Center, University of Fukui, Yoshida-gun 910-1193 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Ueda, Masashi [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan); Radioisotopes Research Laboratory, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Mori, Hirofumi [Advanced Science Research Center, Kanazawa University, Kanazawa 920-8640 (Japan); Saji, Hideo [Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501 (Japan)

    2009-02-15

    Introduction: Based on the concept of bifunctional radiopharmaceuticals, we have previously developed {sup 186}Re-complex-conjugated bisphosphonate analogs for palliation of painful bone metastases and have demonstrated the utility of these compounds. By applying a similar concept, we hypothesized that a bone-specific directed {sup 90}Y-labeled radiopharmaceutical could be developed. Methods: In this study, 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was chosen as the chelating site, and DOTA was conjugated with 4-amino-1-hydroxybutylidene-1,1-bisphosphonate. [{sup 90}Y]DOTA-complex-conjugated bisphosphonate ([{sup 90}Y]DOTA-HBP) was prepared by coordination with {sup 90}Y, and its biodistribution was studied in comparison to [{sup 90}Y]citrate. Results: In biodistribution experiments, [{sup 90}Y]DOTA-HBP and [{sup 90}Y]citrate rapidly accumulated and resided in the bone. Although [{sup 90}Y]citrate showed a higher level of accumulation in the bone than [{sup 90}Y]DOTA-HBP, the clearances of [{sup 90}Y]DOTA-HBP from the blood and from almost all soft tissues were much faster than those of [{sup 90}Y]citrate. As a result, the estimated absorbed dose ratios of soft tissues to osteogenic cells (target organ) of [{sup 90}Y]DOTA-HBP were lower than those of [{sup 90}Y]citrate. Conclusions: [{sup 90}Y]DOTA-HBP showed superior biodistribution characteristics as a bone-seeking agent and led to a decrease in the level of unnecessary radiation compared to [{sup 90}Y]citrate. Since the DOTA ligand forms a stable complex not only with {sup 90}Y but also with lutetium ({sup 177}Lu), indium ({sup 111}In), gallium ({sup 67/68}Ga), gadolinium (Gd) and so on, complexes of DOTA-conjugated bisphosphonate with various metals could be useful as agents for palliation of metastatic bone pain, bone scintigraphy and magnetic resonance imaging.

  13. Radiopharmaceutical development of radiolabelled peptides

    Energy Technology Data Exchange (ETDEWEB)

    Fani, Melpomeni; Maecke, Helmut R. [University Hospital Freiburg, Department of Nuclear Medicine, Freiburg (Germany)

    2012-02-15

    Receptor targeting with radiolabelled peptides has become very important in nuclear medicine and oncology in the past few years. The overexpression of many peptide receptors in numerous cancers, compared to their relatively low density in physiological organs, represents the molecular basis for in vivo imaging and targeted radionuclide therapy with radiolabelled peptide-based probes. The prototypes are analogs of somatostatin which are routinely used in the clinic. More recent developments include somatostatin analogs with a broader receptor subtype profile or with antagonistic properties. Many other peptide families such as bombesin, cholecystokinin/gastrin, glucagon-like peptide-1 (GLP-1)/exendin, arginine-glycine-aspartic acid (RGD) etc. have been explored during the last few years and quite a number of potential radiolabelled probes have been derived from them. On the other hand, a variety of strategies and optimized protocols for efficient labelling of peptides with clinically relevant radionuclides such as {sup 99m}Tc, M{sup 3+} radiometals ({sup 111}In, {sup 86/90}Y, {sup 177}Lu, {sup 67/68}Ga), {sup 64/67}Cu, {sup 18}F or radioisotopes of iodine have been developed. The labelling approaches include direct labelling, the use of bifunctional chelators or prosthetic groups. The choice of the labelling approach is driven by the nature and the chemical properties of the radionuclide. Additionally, chemical strategies, including modification of the amino acid sequence and introduction of linkers/spacers with different characteristics, have been explored for the improvement of the overall performance of the radiopeptides, e.g. metabolic stability and pharmacokinetics. Herein, we discuss the development of peptides as radiopharmaceuticals starting from the choice of the labelling method and the conditions to the design and optimization of the peptide probe, as well as some recent developments, focusing on a selected list of peptide families, including somatostatin

  14. Radio-embolization for hepatocellular carcinoma; Traitement des carcinomes hepatocellulaires par injection intra-arterielle de radio-isotopes

    Energy Technology Data Exchange (ETDEWEB)

    Raoul, J.L. [Departement d' oncologie medicale, centre Eugene-Marquis, rue de la bataille Flandres-Dunkerque, CS 44229, 35042 Rennes cedex (France); Inserm U911, centre Eugene-Marquis, CS 44229, 35042 Rennes cedex (France); Edeline, J.; Pracht, M.; Boucher, E. [Departement d' oncologie medicale, centre Eugene-Marquis, rue de la bataille Flandres-Dunkerque, CS 44229, 35042 Rennes cedex (France); Rolland, Y. [Departement d' imagerie medicale, centre Eugene-Marquis, CS 44229, 35042 Rennes cedex (France); Garin, E. [Inserm U911, centre Eugene-Marquis, CS 44229, 35042 Rennes cedex (France); Departement d' imagerie medicale, centre Eugene-Marquis, CS 44229, 35042 Rennes cedex (France)

    2011-02-15

    Hepatocellular carcinoma is now a major public health concern. In intermediate stages (one third of hepatocellular carcinoma patients), chemo-embolization is the standard of care despite a poor tolerance and a moderate efficacy. Moreover, despite recent improvements, this technique seems in a dead end. Radio-embolization could be an excellent tool for such patients. Currently {sup 131}I-Lipiodol, {sup 188}Re-Lipiodol, {sup 90}Y-glass or resin microspheres are available. More recent and promising data come from microspheres, but phase II and III studies are needed before drawing any conclusion. In the future, the combination of radio-embolization with systemic chemotherapy or targeted agents (particularly anti-angiogenic drugs) seems very promising. (authors)

  15. [Advances in research on radioiodine therapy of carcinoma mediated by gene transfer technology].

    Science.gov (United States)

    Mu, Da; Kuang, Anren

    2010-10-01

    Radioiodine therapy of carcinoma could be mediated by transferring the genes which participate in the process of iodine metabolism in thyroid. The correlative genes are sodium/iodine symporter gene, thyroid peroxidase gene and the specific thyroid transcription factors, and others. The objective gene can specifically express in carcinoma by inserting the tissue-specific promoter/enhancer upstream of them, so radioiodine could be used to treat varied carcinomas. The radioiodine uptake in carcinoma cells was obviously increased and the radioiodine therapy of carcinoma was effective after those genes had expressed in carcinoma cells. The main problem was that the effective half-time of radioiodine in cells was too short to produce the ideal effect of radioiodine therapy. Moreover, 211At and 188Re could be transferred by sodium/iodine symporter and they could be used to treat the carcinoma that is capable of radioiodine uptake.

  16. Influence of voxel size on specific absorbed fractions and S-values in a mouse voxel phantom.

    Science.gov (United States)

    Mohammadi, A; Kinase, S

    2011-02-01

    Photon and electron specific absorbed fractions (SAFs) and S-values have been evaluated using mouse voxel phantoms. In voxel phantoms, it is important to choose the voxel size carefully since it affects the accuracy of results. In this study, two mouse voxel phantoms were constructed, with cubic voxels, one with 0.1-mm sides and the other with 0.4-mm sides. The sources were considered to be distributed uniformly in the main organs and the radiation transport was simulated using the Monte Carlo code EGS4. It was found that the effect of voxel size on SAFs for self-irradiation was not high (voxel size was investigated on S-values for some beta emitters such as (131)I, (153)Sm, (188)Re and (90)Y.

  17. A Brief Review of Chelators for Radiolabeling Oligomers

    Directory of Open Access Journals (Sweden)

    Yuxia Liu

    2010-05-01

    Full Text Available The chemical modification of oligomers such as DNA, PNA, MORF, LNA to attach radionuclides for nuclear imaging and radiotherapy applications has become a field rich in innovation as older methods are improved and new methods are introduced. This review intends to provide a brief overview of several chelators currently in use for the labeling of oligomers with metallic radionuclides such as 99mTc, 111In and 188Re. While DNA and its analogs have been radiolabeled with important radionuclides of nonmetals such as 32P, 35S, 14C, 18F and 125I, the labeling methods for these isotopes involve covalent chemistry that is quite distinct from the coordinate-covalent chelation chemistry described herein. In this review, we provide a summary of the several chelators that have been covalently conjugated to oligomers for the purpose of radiolabeling with metallic radionuclides by chelation and including details on the conjugation, the choice of radionuclides and labeling methods.

  18. Production of tungsten-188 and osmium-194 in a nuclear reactor for new clinical generators

    Energy Technology Data Exchange (ETDEWEB)

    Mirzadeh, S.; Knapp, F.F. Jr.; Callahan, A.P.

    1991-01-01

    Rhenium-188 and iridium-194 are potential candidates for radioimmunotherapy with monoclonal antibodies directed against tumor-associated antigens. Both nuclei are short-lived and decay by high energy {Beta}{minus} emission. In addition, both nuclei emit {gamma}-rays with energy suitable for imaging. An important characteristics is availability of {sup 188}Re and {sup 194}Ir from decay of reactor-produced parents ({sup 188}W and {sup 194}Os, respectively) in convenient generator systems. The {sup 188}W and {sup 194}Os are produced by double neutron capture of {sup 186}W and {sup 192}Os, respectively. The large scale production yields of {sup 188}W in several nuclear reactors will be presented. We also report a new management for the cross-section of {sup 193}Os(n,{gamma}){sup 194}Os reaction and discuss the feasibility of producing sufficient quantities of {sup 194}Os. 17 refs., 1 fig., 2 tabs.

  19. A phase I study of combined docetaxel and repeated high activity {sup 186}Re-HEDP in castration-resistant prostate cancer (CRPC) metastatic to bone (the TAXIUM trial)

    Energy Technology Data Exchange (ETDEWEB)

    Dodewaard-de Jong, Joyce M. van; Bloemendal, Haiko J. [Meander Medical Centre, Department of Internal Medicine, Amersfoort (Netherlands); Klerk, John M.H. de; Haas, Marie J. de [Meander Medical Centre, Department of Nuclear Medicine, Amersfoort (Netherlands); Bezooijen, Bart P.J. van [Meander Medical Centre, Department of Urology, Amersfoort (Netherlands); Wilson, Richard H.; O' Sullivan, Joe M. [Queen' s University Belfast, Centre for Cancer Research and Cell Biology, Belfast, N. Ireland (United Kingdom)

    2011-11-15

    Bone-seeking radiopharmaceuticals have palliative benefit in castration-resistant prostate cancer (CRPC) metastatic to bone. Recent studies have shown improvement of survival and quality of life when radiopharmaceuticals were given repeatedly or in combination with chemotherapy. We designed a phase I study combining docetaxel and {sup 186}Re-labelled hydroxyethylidene diphosphonate (HEDP) in men with CRPC and bone metastases to evaluate toxicity. A dose escalation schedule was designed consisting of four dose levels with a standard dosage of docetaxel (75 mg/m{sup 2} 3-weekly). {sup 186}Re-HEDP was given in increasing activities (1,250 MBq up to 2,500 MBq) after the third and sixth cycle of docetaxel. Dose limiting toxicity (DLT) was defined as any grade 4 toxicity lasting more than 7 days or any grade 3 toxicity that did not recover within 10 days. Three patients were planned for each dose level expanding to six if a DLT occurred. Fourteen patients were recruited with a median age of 64.6 years. One DLT, grade 3 thrombocytopenia lasting >10 days, occurred at dose level 3 leading to expansion of this group to six. One of these patients had an episode of acute renal failure which resolved. Because of production problems of {sup 186}Re-HEDP dose level 4 was not started. Combined therapy with docetaxel and {sup 186}Re-HEDP is generally well tolerated in patients with CRPC metastatic to bone. We will conduct a randomized phase II study using three cycles of docetaxel 75 mg/m{sup 2} 3-weekly followed by {sup 188}Re-HEDP 40 MBq/kg body weight, followed by another three cycles of docetaxel 75 mg/m{sup 2}, followed by {sup 188}Re-HEDP 20 MBq/kg body weight. (orig.)

  20. Targeted Radiotherapy of Estrogen Receptor Positive Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Raghavan Rajagopalan

    2006-08-31

    The overall objectives of the proposal were to develop estrogen receptor (ER) binding small molecule radiopharmaceuticals for targeted radiotherapy of ER positive (ER+) tumors. In particular, this proposal focused on embedding a {sup 186,188}Re or a {sup 32}P radionuclide into an estrogen steroidal framework by isosteric substitution such that the resulting structure is topologically similar to the estrogen (estrogen mimic). The estrogen mimic molecules expected to bind to the ER and exhibit biodistribution akin to that of native estrogen due to structural mimicry. It is anticipated that the {sup 186,188}Re- or a {sup 32}P-containing estrogen mimics will be useful for targeted molecular radiotherapy of ER+ tumors. It is well established that the in vivo target tissue uptake of estrogen like steroidal molecules is related to the binding of the steroids to sex hormone binding globulin (SHBG). SHBG is important in the uptake of estrogens and testosterone in target tissues by SHBG receptors on the cell surface. However, hitherto the design of estrogen like small molecule radiopharmaceuticals was focused on optimizing ER binding characteristics without emphasis on SHBG binding properties. Consequently, even the molecules with good ER affinity in vitro, performed poorly in biodistribution studies. Based on molecular modeling studies the proposal focused on developing estrogen mimics 1-3 which were topologically similar to native estrogens, and form hydrogen bonds in ER and SHBG in the same manner as those of native estrogens. To this end the technical objectives of the proposal focused on synthesizing the rhenium-estrone and estradiol mimics 1 and 2 respectively, and phosphorous estradiol mimic 3 and to assess their stability and in vitro binding characteristics to ER and SHBG.

  1. {sup 99m}Tc-SSS lipiodol: development and study of its biodistribution following injection intra-hepatic artery of healthy pigs; {sup 99m}Tc-SSS lipiodol: mise au point du marquage et biodistribution apres injection au niveau de l'artere hepatique du porc

    Energy Technology Data Exchange (ETDEWEB)

    Garin, E.; Dazord, L.; Moisan, A.; Lecloirec, J.; Herry, J.Y.; Bourguet, P. [Centre Eugene-Marquis, UPRES EA 1794, Service de Medecine Nucleaire, 35 - Rennes (France); Noiret, N.; Lepareur, N.; Roucoux, A. [Ecole Nationale Superieure de Chimie, UMR CNRS 6052, 35 - Rennes (France); Malbert, C. [Institut National de Recherches Agronomiques (INRA/UMR VP), 35 - Saint Gilles (France); Caulet-Maugendre, S.; Turlin, B. [Centre Hospitalier Universitaire Pontchaillou, Service d' Anatomopathologie, 35 - Rennes (France); Tribut, O. [Centre Hospitalier Universitaire Pontchaillou, Service de Pharmacologie Clinique, 35 - Rennes (France)

    2003-12-01

    Aims. Intra-arterial metabolic radiotherapy with {sup 131}I-lipiodol is a therapeutic approach witch can be used for hepatocellular carcinoma, but several drawbacks limit its use. We report here the development of lipiodol labelling with {sup 99m}Tc and its biodistribution after infusion in the hepatic artery in healthy pigs. In fact, labelling lipiodol with {sup 99m}Tc is the first step towards the development of labelling Lipiodol with {sup 188}Re and {sup 99m}Tc lipiodol could be used for dosimetric purpose. Method. The {sup 99m}Tc lipiodol is obtained after dissolving in lipiodol a lipophilic chelating agent labelled with {sup 99m}Tc: the {sup 99m}Tc-(PhCS3)2(PhCS2). The radiochemical purity was assessed immediately after the labelling and 24 hours later. {sup 99m}Tc-lipiodol was injected through the hepatic artery in 7 pigs. Scintigraphic acquisitions were performed 1 and 24 hours after injection. Pigs were killed after 1 or 24 hours for removal of organs and in vitro counting. Results. The labelling of lipiodol with {sup 99m}Tc is achieved with a very high yield, 96 {+-} 0,8%. The radiochemical purity is satisfactory: 92 {+-} 2,6% immediately after labelling and at least 88 {+-} 3,5% at 24 hours. Scintigraphic acquisitions showed a predominant liver uptake and a faint lung uptake without other site of uptake at one hour and the apparition of a faint digestive elimination at 24 hours. Those results are confirmed by ex-vivo counting. Conclusion. This preliminary study point out that labelling lipiodol with {sup 99m}Tc can be performed with a good yield and a good radiochemical purity. It's biodistribution in healthy pigs is satisfactory. Labelling lipiodol with {sup 188}Re is now under development with the same chelating agent. (author)

  2. Effect of Temperature and Mole Ratio on the Synthesis Yield of Rhenium-Tetrofosmin

    Directory of Open Access Journals (Sweden)

    Widyastuti

    2015-08-01

    Full Text Available Technetium-99m (99mTc tetrofosmin is widely used in nuclear medicine as a diagnostic agent for myocardial perfusion and as a tumor imaging agent. As a parenteral preparation it requires an evaluation of its pharmacokinetics and stability in-vivo. Since 99mTc has a short half-life and is only available in very low concentrations, it is impossible to characterize its chemical properties and presence in the body. Due to this reason, only technetium-99 (T1/2 = 5 × 105 years, which is available in macro quantities, or natural rhenium can be used for this purpose. In this study rhenium-188 (188Re tetrofosmin will be synthesized and applied, because non-radioactive Re can be easily obtained. Synthesis and radiochemical purity analysis of carrier-added 188Re-tetrofosmin were carried out as a model to study the in-vivo stability of technetium-99m tetrofosmin. Rhenium-188 was used as a tracer to identify the formation of rhenium tetrofosmin. Rhenium gluconate was synthesized first prior to the formation of rhenium tetrofosmin. The quality of labeling for both rhenium gluconate and rhenium tetrofosmin was analyzed using paper- and thin-layer chromatography, respectively. Rhenium gluconate can be synthesized with high labeling yield within 1 hour, whereas rhenium tetrofosmin was synthesized both in room temperature and in an elevated temperature with various tetrofosmin-to-rhenium mole ratios.The results showed that heating at 95oC led to a higher yield of more than 90% within 30 minutes. Rhenium tetrofosmin could be produced in high radiochemical purity using an excess of tetrofosmin with mole ratio of 2000. It is concluded that rhenium tetrofosmin could be synthesized through the formation of rhenium gluconate, and a higher yield could be obtained in a shorter time by heating process.

  3. Faecalibacterium prausnitzii supernatant improves intestinal barrier function in mice DSS colitis.

    Science.gov (United States)

    Carlsson, Anders H; Yakymenko, Olena; Olivier, Isabelle; Håkansson, Fathima; Postma, Emily; Keita, Asa V; Söderholm, Johan D

    2013-10-01

    OBJECTIVE. The intestinal microbiota plays a substantial role in the pathogenesis of inflammatory bowel disease (IBD). Faecalibacterium prausnitzii (FP) is underrepresented in IBD patients and have been suggested to have anti-inflammatory effects in mice. Increased intestinal permeability is common in IBD but the relationship between FP and intestinal barrier function has not been investigated. Our aim was to study treatment with FP supernatant on intestinal barrier function in a dextran sodium sulfate (DSS) colitis mice model. MATERIAL AND METHODS. C57BL/6 mice received 3% DSS in tap water ad libitum during five days to induce colitis. From day 3 the mice received a daily gavage with FP supernatant or broth during seven days. Ileum and colon were mounted in Ussing chambers for permeability studies with (51)Cr-EDTA and Escherichia coli K-12. Colon was saved for Western blot analyses of tight junction proteins. RESULTS. DSS-treated mice showed significant weight loss and colon shortening. Gavage with FP supernatant resulted in a quicker recovery after DSS treatment and less extensive colonic shortening. Ileal mucosa of DSS mice showed a significant increase in (51)Cr-EDTA-passage compared to controls. (51)Cr-EDTA passage was significantly decreased in mice receiving FP supernatant. No significant differences were observed in passage of E. coli K12. Western blots showed a trend to increased claudin-1 and claudin-2 expressions in DSS mice. CONCLUSIONS. Supernatant of FP enhances the intestinal barrier function by affecting paracellular permeability, and may thereby attenuate the severity of DSS-induced colitis in mice. These findings suggest a potential role of FP in the treatment of IBD.

  4. Cross-section measurements for the formation of manganese-52 and its isolation with a non-hazardous eluent

    Energy Technology Data Exchange (ETDEWEB)

    Buchholz, M.; Spahn, I.; Scholten, B.; Coenen, H.H. [Forschungszentrum Juelich GmbH (Germany). Inst. fuer Neurowissenschaften und Medizin (INM-5: Nuklearchemie)

    2013-10-01

    With respect to the production of no-carrier-added {sup 52}Mn nuclear reactions on natural chromium were investigated. Cross sections of the reactions {sup nat}Cr(p,x){sup 48}V, {sup 48,49,51}Cr, {sup 52g,m}Mn were determined in the proton energy range of 7.6 to 45 MeV. Additionally, production yields of {sup 52g,m}Mn and {sup 51}Cr were measured in the energy range from 8.2 to 16.9 MeV and therefrom the calculated saturation thick target yields were obtained as (2.55 {+-} 0.31), (6.96 {+-} 0.57), and (1.53 {+-} 0.15)GBq/{mu}A, respectively. For in vivo applications like PET, low toxicity is critical and sufficient activity of a radiolabelled compounds mandatory. Thus, additional purification steps after separation of radionuclides and target materials have to be avoided. However, no isolation procedure has been reported in the literature so far where radiomanganese is directly obtained in a non-hazardous solution. Therefore a new separation procedure was developed utilizing the cation-exchange resin DOWEX 50W x 8 (H{sup +}-form). {sup 52g}Mn was quantitatively isolated from 'bulk' chromium after 3 to 4 h in non-hazardous 0.067 M ammonium citrate solution. Up to 99% of {sup 52g}Mn activity was harvested within 10 to 15 mL eluent solution with no measureable {sup 51}Cr impurities. (orig.)

  5. Prediction of renal function (GFR) from cystatin C and creatinine in children: Body cell mass increases accuracy of the estimate

    DEFF Research Database (Denmark)

    Andersen, Trine Borup; Jødal, Lars; Bøgsted, Martin

    AIM: To derive an accurate prediction model for estimating glomerular filtration rate (GFR) in children based primarily on the endogenous renal function marker cystatin C (CysC) and body cell mass (BCM). THEORY: Cystatin C is produced at a constant rate in all cells of the body and is excreted...... by glomerular filtration followed by catabolization in the tubular cells. We hypothesized that production rate is proportional to body cell mass (BCM) and inferred GFR (mL/min) to be proportional to BCM/CysC. MATERIAL AND METHODS: GFR was determined with 51Cr-EDTA-clearance in 131 children (52 girls, 79 boys...

  6. GFR prediction from cystatin C and creatinine in children: body cell mass increases accuracy of the estimate

    DEFF Research Database (Denmark)

    Andersen, Trine Borup; Jødal, Lars; Bøgsted, Martin

    AIM: To derive an accurate prediction model for estimating glomerular filtration rate (GFR) in children based primarily on the endogenous renal function marker cystatin C (CysC) and body cell mass (BCM). THEORY: Cystatin C is produced at a constant rate in all cells of the body and is excreted...... by glomerular filtration followed by catabolization in the tubular cells. We hypothesized that production rate is proportional to body cell mass (BCM) and inferred GFR (mL/min) to be proportional to BCM/CysC. MATERIAL AND METHODS: GFR was determined with 51Cr-EDTA-clearance in 131 children (52 girls, 79 boys...

  7. Effect of metabolic regulation on renal leakiness to dextran molecules in short-term insulin-dependent diabetics

    DEFF Research Database (Denmark)

    Parving, H H; Rutili, F; Granath, K;

    1979-01-01

    Renal clearance of dextran of two ranges of molecular size and glomerular filtration rate (GFR, 51Cr-EDTA) were measured in seven short-term insulin-dependent diabetics (mean age 25 years). Measurements were carried out in the same patient during good and poor metabolic regulation (plasma glucose...... were normalized within one to three weeks of effective insulin treatment. This rapid reversibility can hardly be explained by the previously demonstrated enlargement in glomerular size and filtration surface area, since these alterations remain unchanged after more than one month of insulin treatment...

  8. Myocardial capillary permeability for small hydrophilic indicators during normal physiological conditions and after ischemia and reperfusion

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup

    1991-01-01

    of the injected indicator molecules in an extracted and a transmitted fraction of molecules. In open chest dog hearts measurements performed during normal physiological conditions gave mean capillary extraction values of 43.5-47.5% and the corresponding calculated PdS values were 47.1 - 57.5 ml.(100g.min)-1. From......Myocardial capillary permeability for small hydrophilic solutes (51Cr-EDTA or 99mTc-DTPA) has been measured using intracoronary indicator bolus injection and external radioactivity registration (the single injection, residue detection method). The method is based on kinetic separation...

  9. Comparative study of two drying techniques used in radioactive source preparation: freeze-drying and evaporation using hot dry nitrogen jets.

    Science.gov (United States)

    Branger, T; Bobin, C; Iroulart, M-G; Lépy, M-C; Le Garrères, I; Morelli, S; Lacour, D; Plagnard, J

    2008-01-01

    Quantitative solid sources are used widely in the field of radionuclide metrology. With the aim to improve the detection efficiency for electrons and x-rays, a comparative study between two source drying techniques has been undertaken at LNE-Laboratoire National Henri Becquerel (LNE-LNHB, France). In this paper, freeze-drying using commercial equipment is compared with a system of drying using hot jets of nitrogen developed at Institute for Reference Materials and Measurements (IRMM, Belgium). In order to characterize the influence of self-absorption, the detection efficiencies for (51)Cr sources have been measured by coincidence counting and photon spectrometry.

  10. Solar neutrino experiments

    Energy Technology Data Exchange (ETDEWEB)

    Hampel, W. [Max-Planck-Institut fuer Kernphysik, Heidelberg (Germany)

    1996-11-01

    The present status of experimental solar neutrino research is reviewed. Updated results from the Homestake, Kamiokande, GALLEX and SAGE detectors all show a deficit when compared to recent standard solar model calculations. Two of these detectors, GALLEX and SAGE, have recently been checked with artificial {sup 51}Cr neutrino sources. It is shown that astrophysical scenarios to solve the solar neutrino problems are not favoured by the data. There is hope that the results of forthcoming solar neutrino experiments can provide the answers to the open questions. (author) 6 figs., 3 tabs., 36 refs.

  11. Rapid decline in glomerular filtration rate during the first weeks following heart transplantation

    DEFF Research Database (Denmark)

    Hornum, M; Andersen, M; Gustafsson, F;

    2011-01-01

    We hypothesized that a decrease in renal function is seen immediately after heart transplantation (HTX) with little recovery over time. Twelve consecutive patients had their glomerular filtration rate (GFR) measured using (51)Cr-ethylenediaminetetraacetic acid (EDTA) measured GFR (mGFR) before...... transplantation and at 1, 2, 3, and 26 weeks after transplantation. The mGFR decreased by 28% and 24% during the first 3 and 26 weeks, respectively, with mean blood cyclosporine concentration as an independent risk factor for the decrease in mGFR. The identification of cyclosporine A (CsA) as the most important...

  12. Urinary Neutrophil Gelatinase-Associated Lipocalin and Progression of Diabetic Nephropathy in Type 1 Diabetic Patients in a Four-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Hansen, Henrik Post; Jensen, Berit Ruud

    2010-01-01

    Background: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. Methods: As a substudy of a 4......-year randomized, intervention study evaluating low-protein diet in T1D patients with diabetic nephropathy, 78 patients were studied with yearly measurements of u-NGAL (ELISA, BioPorto). Outcome: Decline in glomerular filtration rate (GFR) ((51)Cr-EDTA), and end-stage renal disease (ESRD) or death...

  13. On the search of sterile neutrinos by oscillometry measurements

    CERN Document Server

    Vergados, J D; Novikov, Yu N

    2011-01-01

    It is shown that the "new" neutrino with a high mass squared difference and a small mixing angle should reveal itself in the oscillometry measurements. For a judicious monochromatic neutrino source the "new" oscillation length $L_{42}$ is expected shorter than 1.5 m. Thus the needed measurements can be implemented with a gaseous spherical TPC of modest dimensions with a very good energy and position resolution. The best candidates for oscillometry are discussed and the sensitivity to the mixing angle $\\theta_{14}$ has been estimated: $\\sin^2{(2\\theta_{14})}$=0.05 (99{%}) for two months of data handling with $^{51}$Cr.

  14. Quantitation of erythropoiesis in myelomatosis

    DEFF Research Database (Denmark)

    Birgens, H S; Hansen, O P; Henriksen, Jens Henrik Sahl;

    1979-01-01

    ) and the Red Blood Cell Iron Turnover (RBCIT) varied from subnormal to values markedly increased above upper normal limit. The calculated average Mean Red Cell Life time (MRCL) of erythrocytes was just below normal range. The mean Marrow Transit Time (MTT) was normal in the patients, despite subnormal venous...... haematocrit, indicating insufficient stimulation of the bone marrow. The renal function, measured as 51Cr-EDTA clearance, was found positively correlated to the RBCIT (r = 0.78, P less than 0.05). The results suggest that the previously demonstrated relationship between anaemia and renal failure in patients...

  15. Deficient natural killer cell function in preeclampsia

    Energy Technology Data Exchange (ETDEWEB)

    Alanen, A.; Lassila, O.

    1982-11-01

    Natural killer cell activity of peripheral blood lymphocytes was measured against K-562 target cells with a 4-hour /sup 51/Cr release assay in 15 primigravid women with preeclamptic symptoms. Nineteen primigravid women with an uncomplicated pregnancy and 18 nonpregnant women served as controls. The natural killer cell activity of preeclamptic women was observed to be significantly lower than that of both control groups. Natural killer cells in preeclamptic women responded normally to augmentation caused by interferon. These findings give further evidence for the participation of the maternal immune system in this pregnancy disorder.

  16. Initial effect of enalapril on kidney function in patients with moderate to severe chronic nephropathy

    DEFF Research Database (Denmark)

    Kamper, A L; Thomsen, H S; Nielsen, S L

    1990-01-01

    Angiotensin converting enzyme (ACE) inhibitors has been suggested to halt the progression of chronic renal failure. As the initial step of a controlled trial of this hypothesis, it was investigated whether start of enalapril in patients with severe chronic nephropathy might cause a critical fall...... in their renal function. Thirty-one patients were studied, 26 on chronic antihypertensive treatment with drugs other than ACE inhibitors and 5 untreated normotensive. 51Cr-EDTA plasma clearance and renal technetium-99m dimercaptosuccinic acid (99mTc-DMSA) scintigraphy were made before and 24 h after start...

  17. Natural killer cell cytotoxicity assay with time-resolved fluorimetry

    Institute of Scientific and Technical Information of China (English)

    李建中; 章竹君; 金伯泉; 田方

    1996-01-01

    A new time-resolved fluorimetric method for the measurement of natural killer (NK) cell cytotoxicity has been developed by labelling the target cell K562 with a new synthesized fluorescence marker KLUK. The method has advantages of higher sensitivity, time-saving, good reproducibility and has no radioactivity problems. A satisfactory result is obtained by comparing it with 51Cr release method. It demonstrates that the new marker provides an alternative to currently used radioactive markers for the assessment of in vitro cellular cytotoxicity.

  18. Acute pain induces an instant increase in natural killer cell cytotoxicity in humans and this response is abolished by local anaesthesia

    DEFF Research Database (Denmark)

    Greisen, J.; Hokland, Marianne; Grøfte, Thorbjørn

    1999-01-01

    to abdominal skin for 30 min to an intensity of 8 on a visual analogue scale (0-10). Next, the electric intensity profile was reproduced during local anaesthesia (mepivacaine 10 mg ml-1 s.c. to a total dose of 2.5 mg kg-1). NK cell cytotoxicity was measured using a 4-h 51Cr-release assay against K562 target...... not change either NK cell activity or number. Parallel and significant increases in concentrations of plasma epinephrine and serum cortisol were observed. These changes were abolished by local anaesthesia. We conclude that acute severe pain without tissue injury markedly increased NK cell cytotoxicity. Local...

  19. Capillary permeability of 99mTc-DTPA in canine myocardium determined by intracoronary bolus injection and residue detection

    DEFF Research Database (Denmark)

    Svendsen, Jesper Hastrup; Efsen, F; Haunsø, S

    1989-01-01

    Capillary permeability of 99mtechnetium-diethylenetriaminepenta-acetic acid (99mTc-DTPA; MW 485.0) and 51chromium-ethylenediaminetetra-acetate (51Cr-EDTA; MW 340.2) was studied in an in vivo canine heart preparation by the single injection, residue detection (SIRD) method. In experiments on open...... chest dogs (group A) these indicators were administered separately as bolus injections into a cannulated diagonal branch of the left anterior descending coronary artery (LAD) and the curve of the response function was recorded by external activity registration. In further experiments on closed and open...

  20. Assessment of predictors of response and long-term survival of patients with neuroendocrine tumour treated with peptide receptor chemoradionuclide therapy (PRCRT)

    Energy Technology Data Exchange (ETDEWEB)

    Kong, G.; Thompson, M.; Johnston, V.; Eu, P. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); Collins, M.; Herschtal, A. [Peter MacCallum Cancer Centre, Department of Biostatistics and Clinical Trials, Melbourne, VIC (Australia); Hofman, M.S.; Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, East Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Michael, M. [The University of Melbourne, Department of Medicine, Melbourne, VIC (Australia); Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia)

    2014-10-15

    To review the response and outcomes of {sup 177}Lu-DOTA-octreotate chemoradionuclide therapy (LuTate PRCRT) in patients with neuroendocrine tumour (NET) expressing high levels of somatostatin receptors with uncontrolled symptoms or disease progression. A total of 68 patients (39 men; 17 - 76 years of age) who had completed an induction course of at least three cycles of LuTate PRCRT between January 2006 and June 2010 were reviewed. Ten patients were treated for uncontrolled symptoms and 58 had disease progression despite conventional treatment. The majority had four induction LuTate cycles (median treatment duration 5 months and cumulative activity 31 GBq), and 63 patients had concomitant 5-FU radiosensitizing infusional chemotherapy. Factors predicting overall survival were assessed using the log-rank test and Cox proportional hazards regression. Of those treated for uncontrolled symptoms, 70 % received benefit maintained for at least 6 months after treatment. Among patients with progressive disease 68 % showed stabilization or regression on CT, 67 % on molecular imaging and 56 % biochemically up to 12 months after treatment; 32 patients died. Overall survival rates at 2 and 5 year were 72.1 % and 52.1 %, respectively. Median overall survival was not estimable at a median follow-up of 60 months (range 5 - 86 months). Nonpancreatic primary sites, dominant liver metastases, lesion size <5 cm and the use of 5-FU chemotherapy were statistically significantly associated with objective response. A disseminated pattern and a high disease burden (whole-body retention index) were associated with an increased risk of death. Objective biochemical, molecular imaging and CT responses were all associated with longer overall survival. A high proportion of patients with progressive NET or uncontrolled symptoms received therapeutic benefit from LuTate with concomitant 5-FU chemotherapy. The achievement of objective biochemical, molecular or CT responses within 12 months was

  1. DOTA-functionalized polylysine: a high number of DOTA chelates positively influences the biodistribution of enzymatic conjugated anti-tumor antibody chCE7agl.

    Directory of Open Access Journals (Sweden)

    Jürgen Grünberg

    Full Text Available Site-specific enzymatic reactions with microbial transglutaminase (mTGase lead to a homogenous species of immunoconjugates with a defined ligand/antibody ratio. In the present study, we have investigated the influence of different numbers of 1,4,7,10-tetraazacyclododecane-N-N'-N''-N'''-tetraacetic acid (DOTA chelats coupled to a decalysine backbone on the in vivo behavior of the chimeric monoclonal anti-L1CAM antibody chCE7agl. The enzymatic conjugation of (DOTA1-decalysine, (DOTA3-decalysine or (DOTA5-decalysine to the antibody heavy chain (via Gln295/297 gave rise to immunoconjugates containing two, six or ten DOTA moieties respectively. Radiolabeling of the immunoconjugates with (177Lu yielded specific activities of approximately 70 MBq/mg, 400 MBq/mg and 700 MBq/mg with increasing numbers of DOTA chelates. Biodistribution experiments in SKOV3ip human ovarian cancer cell xenografts demonstrated a high and specific accumulation of radioactivity at the tumor site for all antibody derivatives with a maximal tumor accumulation of 43.6±4.3% ID/g at 24 h for chCE7agl-[(DOTA-decalysine]2, 30.6±12.0% ID/g at 24 h for chCE7agl-[(DOTA3-decalysine]2 and 49.9±3.1% ID/g at 48 h for chCE7agl-[(DOTA5-decalysine]2. The rapid elimination from the blood of chCE7agl-[(DOTA-decalysine]2 (1.0±0.1% ID/g at 24 h is associated with a high liver accumulation (23.2±4.6% ID/g at 24 h. This behavior changed depending on the numbers of DOTA moieties coupled to the decalysine peptide with a slower blood clearance (5.1±1.0 (DOTA3 versus 11.7±1.4% ID/g (DOTA5, p<0.005 at 24 h and lower radioactivity levels in the liver (21.4±3.4 (DOTA3 versus 5.8±0.7 (DOTA5, p<0.005 at 24 h. We conclude that the site-specific and stoichiometric uniform conjugation of the highly DOTA-substituted decalysine ((DOTA5-decalysine to an anti-tumor antibody leads to the formation of immunoconjugates with high specific activity and excellent in vivo behavior and is a valuable option for

  2. Cathepsin S-cleavable, multi-block HPMA copolymers for improved SPECT/CT imaging of pancreatic cancer.

    Science.gov (United States)

    Fan, Wei; Shi, Wen; Zhang, Wenting; Jia, Yinnong; Zhou, Zhengyuan; Brusnahan, Susan K; Garrison, Jered C

    2016-10-01

    This work continues our efforts to improve the diagnostic and radiotherapeutic effectiveness of nanomedicine platforms by developing approaches to reduce the non-target accumulation of these agents. Herein, we developed multi-block HPMA copolymers with backbones that are susceptible to cleavage by cathepsin S, a protease that is abundantly expressed in tissues of the mononuclear phagocyte system (MPS). Specifically, a bis-thiol terminated HPMA telechelic copolymer containing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) was synthesized by reversible addition-fragmentation chain transfer (RAFT) polymerization. Three maleimide modified linkers with different sequences, including cathepsin S degradable oligopeptide, scramble oligopeptide and oligo ethylene glycol, were subsequently synthesized and used for the extension of the HPMA copolymers by thiol-maleimide click chemistry. All multi-block HPMA copolymers could be labeled by (177)Lu with high labeling efficiency and exhibited high serum stability. In vitro cleavage studies demonstrated highly selective and efficient cathepsin S mediated cleavage of the cathepsin S-susceptible multi-block HPMA copolymer. A modified multi-block HPMA copolymer series capable of Förster Resonance Energy Transfer (FRET) was utilized to investigate the rate of cleavage of the multi-block HPMA copolymers in monocyte-derived macrophages. Confocal imaging and flow cytometry studies revealed substantially higher rates of cleavage for the multi-block HPMA copolymers containing the cathepsin S-susceptible linker. The efficacy of the cathepsin S-cleavable multi-block HPMA copolymer was further examined using an in vivo model of pancreatic ductal adenocarcinoma. Based on the biodistribution and SPECT/CT studies, the copolymer extended with the cathepsin S susceptible linker exhibited significantly faster clearance and lower non-target retention without compromising tumor targeting. Overall, these results indicate that

  3. Synthesis of phosphine and antibody-azide probes for in vivo Staudinger ligation in a pretargeted imaging and therapy approach.

    Science.gov (United States)

    Vugts, Danielle J; Vervoort, Annelies; Stigter-van Walsum, Marijke; Visser, Gerard W M; Robillard, Marc S; Versteegen, Ron M; Vulders, Roland C M; Herscheid, J Koos D M; van Dongen, Guus A M S

    2011-10-19

    The application of intact monoclonal antibodies (mAbs) as targeting agents in nuclear imaging and radioimmunotherapy is hampered by the slow pharmacokinetics of these molecules. Pretargeting with mAbs could be beneficial to reduce the radiation burden to the patient, while using the excellent targeting capacity of the mAbs. In this study, we evaluated the applicability of the Staudinger ligation as pretargeting strategy using an antibody-azide conjugate as tumor-targeting molecule in combination with a small phosphine-containing imaging/therapeutic probe. Up to 8 triazide molecules were attached to the antibody without seriously affecting its immunoreactivity, pharmacokinetics, and tumor uptake in tumor bearing nude mice. In addition, two (89)Zr- and (67/68)Ga-labeled desferrioxamine (DFO)-phosphines, a (177)Lu-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-phosphine and a (123)I-cubyl phosphine probe were synthesized and characterized for their pharmacokinetic behavior in nude mice. With respect to the phosphine probes, blood levels at 30 min after injection were phosphine, relative to the azide, in aqueous solution resulted in 20-25% efficiency after 2 h. The presence of 37% human serum resulted in a reduced ligation efficiency (reduction max. 30% at 2 h), while the phosphines were still >80% intact. No in vivo Staudinger ligation was observed in a mouse model after injection of 500 μg antibody-azide, followed by 68 μg DFO-phosphine at t = 2 h, and evaluation in blood at t = 7 h. To explain negative results in mice, Staudinger ligation was performed in vitro in mouse serum. Under these conditions, a side product with the phosphine was formed and ligation efficiency was severely reduced. It is concluded that in vivo application of the Staudinger ligation in a pretargeting approach in mice is not feasible, since this ligation reaction is not bioorthogonal and efficient enough. Slow reaction kinetics will also severely restrict the applicability

  4. Radiopharmacy

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2014-07-01

    the regulatory agencies, CNEN and ANVISA; - ANVISA published the regulations for registration of radiopharmaceutical products and for obtaining the GMP accreditation in radiopharmacy. The actions required to comply with these regulations were implemented; - The purchase of a new cyclotron dedicated only to {sup 18}F production has opened several possibilities for the development of new positron emission radioisotopes; - The research and development projects shifted with time to new products for therapy (with {sup 177}Lu, {sup 90}Y and {sup 166}Ho) and for PET ({sup 18}F, {sup 68}Ga, {sup 64}Cu); - Certification and maintenance of the ISO Quality Management System; - A validation master plan was prepared considering the production process and related areas, personnel and material flow procedures were implemented and new equipment have allowed the introduction of modern analytical methods in the quality control. (author)

  5. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Kidd, M. [Wren Laboratories, Branford, CT (United States); Modlin, I.M. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Yale School of Medicine, New Haven, CT (United States); Severi, S.; Nicolini, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Drozdov, I. [Bering Limited, London (United Kingdom); Kwekkeboom, D.J.; Krenning, E.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Erasmus Medical Center, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2016-05-15

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with {sup 177}Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 {sup 18}FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ{sup 2} = 27.4; p = 1.2 x 10{sup -7}) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0

  6. Comparison of biological stability and metabolism of CCK2 receptor targeting peptides, a collaborative project under COST BM0607

    Energy Technology Data Exchange (ETDEWEB)

    Ocak, Meltem [Innsbruck Medical University, Clinical Department of Nuclear Medicine, Innsbruck (Austria); Istanbul University, Department of Pharmaceutical Technology, Pharmacy Faculty, Istanbul (Turkey); Helbok, Anna; Rangger, Christine; Decristoforo, Clemens [Innsbruck Medical University, Clinical Department of Nuclear Medicine, Innsbruck (Austria); Peitl, Petra Kolenc [University Medical Centre Ljubljana, Department for Nuclear Medicine, Ljubljana (Slovenia); Nock, Berthold A. [National Center for Scientific Research Demokritos, Molecular Radiopharmacy, Institute of Radioisotopes-Radiodiagnostic Products, Athens (Greece); Morelli, Giancarlo [University of Naples ' ' Federico II' ' and IBB-CN, Department of Biological Sciences, CIRPeB, Naples (Italy); Eek, Annemarie [Radboud University Nijmegen Medical Centre, Department of Nuclear Medicine, Nijmegen (Netherlands); Sosabowski, Jane K. [Institute of Cancer, Barts and the London Queen Mary' s School of Medicine and Dentistry, Centre for Molecular Oncology and Imaging, London (United Kingdom); Breeman, W.A.P. [Erasmus MC Rotterdam, Department of Nuclear Medicine, Rotterdam (Netherlands); Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research Institute of Pathology, Berne (Switzerland)

    2011-08-15

    Stability of radiolabelled cholecystokinin 2 (CCK2) receptor targeting peptides has been a major limitation in the use of such radiopharmaceuticals especially for targeted radionuclide therapy applications, e.g. for treatment of medullary thyroid carcinoma (MTC). The purpose of this study was to compare the in vitro stability of a series of peptides binding to the CCK2 receptor [selected as part of the COST Action on Targeted Radionuclide Therapy (BM0607)] and to identify major cleavage sites. Twelve different 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-minigastrin/CCK conjugates were provided within an European COST Action (BM0607) by different laboratories and radiolabelled with {sup 177}Lu. Their in vitro stabilities were tested in fresh human serum. Radiochemical yields (RCY) and intact radioligands for half-life calculations were determined by radio-HPLC. Matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) analysis of metabolites was performed to identify cleavage products using conjugates labelled with excess stable {sup nat}Lu, incubated in serum at 37 C. Urine metabolite analysis after injection in normal mice was performed by radio-HPLC analysis. Variable stability in human serum was found for the different peptides with calculated half-lives between 4.5 {+-} 0.1 h and 198 {+-} 0.1 h (n = 2). In urine of normal mice only metabolised peptide fragments were detected even at short times after injection for all peptides. MALDI-TOF MS revealed a major cleavage site of all minigastrin derivatives between Asp and Phe-NH{sub 2} at the C-terminal end. Development of CCK2 receptor ligands especially for therapeutic purposes in patients with MTC or small cell lung cancer (SCLC) is still ongoing in different laboratories. This comparative study provided valuable insight into the importance of biological stability especially in the context of other results of this comparative

  7. The NUKDOS software for treatment planning in molecular radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Kletting, Peter; Schimmel, Sebastian [Univ. Ulm (Germany). Klinik fuer Nuklearmedizin; Haenscheid, Heribert; Fernandez, Maria; Lassmann, Michael [Univ. Wuerzburg (Germany). Klinik fuer Nuklearmedizin; Luster, Markus [Univ. Marburg (Germany). Klinik fuer Nuklearmedizin; Nosske, Dietmar [Bundesamt fuer Strahlenschutz, Fachbereich Strahlenschutz und Gesundheit, Oberschleissheim (Germany); Glatting, Gerhard [Heidelberg Univ., Medical Radiation Physics/Radiation Protection, Mannheim (Germany)

    2015-07-01

    The aim of this work was the development of a software tool for treatment planning prior to molecular radiotherapy, which comprises all functionality to objectively determine the activity to administer and the pertaining absorbed doses (including the corresponding error) based on a series of gamma camera images and one SPECT/CT or probe data. NUKDOS was developed in MATLAB. The workflow is based on the MIRD formalism For determination of the tissue or organ pharmacokinetics, gamma camera images as well as probe, urine, serum and blood activity data can be processed. To estimate the time-integrated activity coefficients (TIAC), sums of exponentials are fitted to the time activity data and integrated analytically. To obtain the TIAC on the voxel level, the voxel activity distribution from the quantitative 3D SPECT/CT (or PET/CT) is used for scaling and weighting the TIAC derived from the 2D organ data. The voxel S-values are automatically calculated based on the voxel-size of the image and the therapeutic nuclide ({sup 90}Y, {sup 131}I or {sup 177}Lu). The absorbed dose coefficients are computed by convolution of the voxel TIAC and the voxel S-values. The activity to administer and the pertaining absorbed doses are determined by entering the absorbed dose for the organ at risk. The overall error of the calculated absorbed doses is determined by Gaussian error propagation. NUKDOS was tested for the operation systems Windows {sup registered} 7 (64 Bit) and 8 (64 Bit). The results of each working step were compared to commercially available (SAAMII, OLINDA/EXM) and in-house (UlmDOS) software. The application of the software is demonstrated using examples form peptide receptor radionuclide therapy (PRRT) and from radioiodine therapy of benign thyroid diseases. For the example from PRRT, the calculated activity to administer differed by 4% comparing NUKDOS and the final result using UlmDos, SAAMII and OLINDA/EXM sequentially. The absorbed dose for the spleen and tumour

  8. Production of Endohedral Fullerenes by Ion Implantation

    Energy Technology Data Exchange (ETDEWEB)

    Diener, M.D.; Alford, J. M.; Mirzadeh, S.

    2007-05-31

    The empty interior cavity of fullerenes has long been touted for containment of radionuclides during in vivo transport, during radioimmunotherapy (RIT) and radioimaging for example. As the chemistry required to open a hole in fullerene is complex and exceedingly unlikely to occur in vivo, and conformational stability of the fullerene cage is absolute, atoms trapped within fullerenes can only be released during extremely energetic events. Encapsulating radionuclides in fullerenes could therefore potentially eliminate undesired toxicity resulting from leakage and catabolism of radionuclides administered with other techniques. At the start of this project however, methods for production of transition metal and p-electron metal endohedral fullerenes were completely unknown, and only one method for production of endohedral radiofullerenes was known. They therefore investigated three different methods for the production of therapeutically useful endohedral metallofullerenes: (1) implantation of ions using the high intensity ion beam at the Oak Ridge National Laboratory (ORNL) Surface Modification and Characterization Research Center (SMAC) and fullerenes as the target; (2) implantation of ions using the recoil energy following alpha decay; and (3) implantation of ions using the recoil energy following neutron capture, using ORNL's High Flux Isotope Reactor (HFIR) as a thermal neutron source. While they were unable to obtain evidence of successful implantation using the ion beam at SMAC, recoil following alpha decay and neutron capture were both found to be economically viable methods for the production of therapeutically useful radiofullerenes. In this report, the procedures for preparing fullerenes containing the isotopes {sup 212}Pb, {sup 212}Bi, {sup 213}Bi, and {sup 177}Lu are described. None of these endohedral fullerenes had ever previously been prepared, and all of these radioisotopes are actively under investigation for RIT. Additionally, the chemistry for

  9. Separation of lanthanides through hydroxyapatite; Separacion de lantanidos mediante hidroxiapatita

    Energy Technology Data Exchange (ETDEWEB)

    Garcia M, F.G

    2006-07-01

    With the objective of obtaining from an independent way to each one of the lanthanides {sup 151} Pm, {sup 161} Tb, {sup 166} Ho and {sup 177} Lu free of carrier and with high specific activities starting from the indirect irradiation via, it intends in this work to determine the viability of separation of the couples Nd/Pm, Dy/Ho, Gd/Tb and Yb/Lu, by means of ion exchange column chromatography, using hydroxyapatite (HAp) and fluorite like absorbent material in complexing media. It is important to mention that have registered separation studies among lanthanides of the heavy group with those of the slight group, using the same mass and, in comparison with this work, quantities different from the father were used and of the son, also, that the separation studies were carried out among neighboring lanthanides. In this investigation, it was determined the effect that its have the complexing media: KSCN, sodium tartrate, sodium citrate, EDTA and aluminon, their pH and concentration, in the adsorption of the lanthanides in both minerals, in order to determine the chromatographic conditions for separation of the couples Nd/Pm, Dy/Ho, Gd/Tb and Yb/Lu. The work consists of five chapters, in the first one they are presented a theoretical introduction of the characteristics more important of the lanthanides, the hydroxyapatite and the fluorite; in the second, it is deepened in the ion exchange, as well as the two techniques (XRD and High Vacuum Electron Microscopy) to make the characterization of LnCI{sub 3} (Ln = Nd, Gd, Dy or Yb) synthesized. The third chapter, it describes the methodology continued in our experimental work; in the room, its are presented the obtained results of the static and dynamic method to determine the viability of separation of neighboring lanthanides; and finally, the five chapter shows the conclusions. In this study, it is concludes that the separation among neighboring lanthanides cannot be carried out in the minerals and used media; because

  10. Demonstration of NK cell-mediated lysis of varicella-zoster virus (VZV)-infected cells: characterization of the effector cells

    Energy Technology Data Exchange (ETDEWEB)

    Tilden, A.B.; Cauda, R.; Grossi, C.E.; Balch, C.M.; Lakeman, A.D.; Whitley, R.J.

    1986-06-01

    Infection with varicella-zoster virus (VZV) rendered RAJI cells more susceptible to lysis by non-adherent blood lymphocytes. At an effector to target ratio of 80:1 the mean percentage of /sup 51/Cr release of VZV-infected RAJI cells was 41 +/- 12%, whereas that of uninfected RAJI cells was 15 +/- 6%. The increased susceptibility to lysis was associated with increased effector to target conjugate formation in immunofluorescence binding assays. The effector cells cytotoxic for VZV-infected RAJI cells were predominantly Leu-11a/sup +/ Leu-4/sup -/ granular lymphocytes as demonstrated by fluorescence-activated cell sorting. The effector cell active against VZV-infected RAJI cells appeared similar to those active against herpes simplex virus (HSV)-infected cells, because in cold target competition experiments the lysis of /sup 51/Cr-labeled VZV-infected RAJI cells was efficiently inhibited by either unlabeled VZV-infected RAJI cells (mean 71% inhibition, 2:1 ratio unlabeled to labeled target) or HSV-infected RAJI cells (mean 69% inhibition) but not by uninfected RAJI cells (mean 10% inhibition). In contrast, competition experiments revealed donor heterogeneity in the overlap between effector cells for VZV- or HSV-infected RAJI vs K-562 cells.

  11. Effects of melanin-induced free radicals on the isolated rat peritoneal mast cells

    Energy Technology Data Exchange (ETDEWEB)

    Ranadive, N.S.; Shirwadkar, S.; Persad, S.; Menon, I.A.

    1986-03-01

    Pheomelanin from human red hair (RHM) produces considerably more cellular damage in Ehrlich ascites carcinoma cells when subjected to radiations of wavelength 320-700 nm than eumelanin from black hair (BHM). Irradiation of RHM generated large amounts of superoxide while BHM did not produce detectable amounts of superoxide. The present investigations describe the effects of irradiation of mast cells in the presence of various natural and synthetic melanins. Irradiation of mast cells in the presence of RHM and red hair melanoprotein released large amounts of histamine while BHM and synthetic melanins prepared from dopa, cysteinyldopa, or a mixture of dopa and cysteinyldopa did not release histamine. The release of histamine at lower concentrations of RHM was not accompanied by the release of /sup 51/Cr from chromium-loaded cells, suggesting that this release was of noncytotoxic nature. On the other hand, the release of histamine at higher concentrations of RHM was due to cell lysis since both histamine and cytoplasmic marker /sup 51/Cr were released to the same extent. The release evoked by large concentration RHM was not inhibited by superoxide dismutase or catalase. This suggests that the cell lysis under these conditions was not due to H/sub 2/O/sub 2/ or O-2. The finding that mast cells release histamine when irradiated in the presence of RHM suggests that the immediate and late-phase reactions seen in sunburn may in part be due to the release of mediators from these cells.

  12. Aspects of osseous, peritoneal and renal handling of bisphosphonate during peritoneal dialysis: a methodological study

    DEFF Research Database (Denmark)

    Joffe, P; Henriksen, Jens Henrik Sahl

    1996-01-01

    to continuous ambulatory peritoneal dialysis (CAPD). The aims were: to assess the kinetics of 99m-technetium MBP (99mTc-MBP) in CAPD, and to evaluate the correctness of the assumption that the peritoneal and renal clearances of 99mTc-MBP equal the total plasma clearance of 51-chromium ethylenediamine tetra......-acetic acid (51Cr-EDTA). Eight patients on CAPD were studied cross-sectionally. The mean plasma clearances of 99mTc-MBP and 51Cr-EDTA in the steady state (4h) were 38.2 and 12.2 ml min-1 (p peritoneal clearances (0-4 h) were 5.2 and 7.2 ml min-1 (p ....5 and 2.8 ml min-1 (not significant), respectively. The bone bisphosphonate clearance (BBC) at steady state was 26.0 ml min-1, a value which was significantly higher than that at infinity (16.5 ml min-1, p peritoneal and renal clearances of 99m...

  13. Flow cytometry evaluation of cell-mediated cytotoxicity.

    Science.gov (United States)

    Zarcone, D; Tilden, A B; Cloud, G; Friedman, H M; Landay, A; Grossi, C E

    1986-11-20

    A novel flow cytometry method for the evaluation of cell-mediated cytotoxicity is described. This method uses flow cytometry analysis to distinguish target cells from effector cells by differences in volume and light scatter characteristics. Non-viable target cells, following their interaction with effector cells, are determined via propidium iodide (PI) dye exclusion and then expressed as a percentage of the total target cell population. This assay is suitable both for analysis of systems which allow recycling of cytotoxic effector cells (total cell cytotoxicity assays, TCCA), and of systems in which recycling does not occur (single cell cytotoxicity assays, SCCA). Natural killer (NK) cell-mediated cytotoxicity evaluated by flow cytometry is significantly correlated with the standard 51Cr release assay. Flow cytometry can also be used to evaluate the competitive inhibition that certain cell types exert on the cell-mediated killing of NK-sensitive targets. A prerequisite for this assay is that competitor cells and target cells are distinguishable through their volume and light scatter characteristics. Advantages and pitfalls of the flow cytometry method are discussed, in comparison with the 51Cr-release assay.

  14. Simplified methods for assessment of renal function as the ratio of glomerular filtration rate to extracellular fluid volume

    DEFF Research Database (Denmark)

    Jødal, Lars; Brøchner-Mortensen, Jens

    2012-01-01

    Background: Instead of scaling glomerular filtration rate (GFR) to a body surface area of 1.73m2, it has been suggested to scale GFR to extracellular fluid volume (ECV). The ratio GFR/ECV has physiological meaning in that it indicates how often ‘that which is to be regulated’ (i.e. ECV) comes...... into contact with the ‘regulator’ (i.e. the kidneys). Aim: The aim of the present study was as follows: to analyse two published calculation methods for determining ECV and GFR/ECV; to develop a new simple and accurate formula for determining ECV; and to compare and evaluate these methods. Materials...... and methods: GFR was determined as 51Cr-EDTA clearance. The study comprised 128 individuals (35 women, 66 men and 27 children) with a full 51Cr-EDTA plasma concentration curve, determined from injection until 4–5 h p.i. Reference values for GFR and ECV were calculated from the full curve. One...

  15. In vitro induction of tumor-specific immunity. VI: analysis of specificity of immune response by cellular competitive inhibition: limitations and advantages of the technique.

    Science.gov (United States)

    Chism, S E; Burton, R C; Grail, D L; Bell, P M; Warner, N L

    1977-01-01

    The cellular competitive inhibition 51Cr-release assay makes two distinct contributions to the in vitro study of cell-mediated immunity. It allows target cells which are not amenable to isotopic labelling to be investigated for their antigenic specificity, and it provides a means, complementary to the direct cytotoxicity assay, of estimating qualitative and quantitative differences in antigen expression on intact normal and neoplastic cells. Various parameters of a micro-51Cr-release inhibition assay have been studied, and it was found that the assay conditions markedly influenced both the sensitivity and specificity. It is concluded that optimal assay conditions for specificity include: 1) moderate levels of lysis on the linear part of the CL/T titration curve, 2) avoidance of prolonged assay times, and 3) low ratios of blocker to target cells. When tumor cells with large cell volumes are used as competitive inhibitor (blocker) cells, non-specific blocking will occur; limits have been defined for this particular micro-inhibition assay which, in general, exclude these effects.

  16. Luciferase mRNA Transfection of Antigen Presenting Cells Permits Sensitive Nonradioactive Measurement of Cellular and Humoral Cytotoxicity

    Directory of Open Access Journals (Sweden)

    Tana A. Omokoko

    2016-01-01

    Full Text Available Immunotherapy is rapidly evolving as an effective treatment option for many cancers. With the emerging fields of cancer vaccines and adoptive cell transfer therapies, there is an increasing demand for high-throughput in vitro cytotoxicity assays that efficiently analyze immune effector functions. The gold standard 51Cr-release assay is very accurate but has the major disadvantage of being radioactive. We reveal the development of a versatile and nonradioactive firefly luciferase in vitro transcribed (IVT RNA-based assay. Demonstrating high efficiency, consistency, and excellent target cell viability, our optimized luciferase IVT RNA is used to transfect dividing and nondividing primary antigen presenting cells. Together with the long-lasting expression and minimal background, the direct measurement of intracellular luciferase activity of living cells allows for the monitoring of killing kinetics and displays paramount sensitivity. The ability to cotransfect the IVT RNA of the luciferase reporter and the antigen of interest into the antigen presenting cells and its simple read-out procedure render the assay high-throughput in nature. Results generated were comparable to the 51Cr release and further confirmed the assay’s ability to measure antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. The assay’s combined simplicity, practicality, and efficiency tailor it for the analysis of antigen-specific cellular and humoral effector functions during the development of novel immunotherapies.

  17. Extract of feverfew inhibits interactions of human platelets with collagen substrates

    Energy Technology Data Exchange (ETDEWEB)

    Loesche, W.M.; Mazurov, A.V.; Heptinstall, S.; Groenewegen, W.A.; Repin, V.S.; Till, U.

    1987-12-01

    The interaction of platelets with surfaces coated with collagens of type III (C III) or IV (C IV) has been studied by measuring the deposition of /sup 51/Cr-labeled platelets and by scanning electron microscopy (SEM). Experiments were performed using platelet-rich plasma (PRP) and suspensions of gel-filtered platelets (GFP). Platelets were deposited on C III mainly as surface-bound aggregates. In contrast they were deposited on C IV mainly as spread forms of individual cells. Formation of aggregates on C III was more extensive for PRP than for GFP; in contrast platelet spreading on C IV was more extensive for GFP than for PRP. The effects of an extract of the plant feverfew on platelet-collagen interactions were determined. Feverfew extract inhibited the deposition of /sup 51/Cr-labeled platelets on both C III and C IV in a dose-dependent way. Similar concentrations of extract were needed to inhibit the formation of surface-bound aggregates and to inhibit platelet spreading in both PRP and GFP.

  18. Activation cross-sections of longer lived products of proton induced nuclear reactions on manganese up to 70 MeV

    Energy Technology Data Exchange (ETDEWEB)

    Ditrói, F., E-mail: ditroi@atomki.hu [Institute for Nuclear Research, Hungarian Academy of Sciences (ATOMKI), Debrecen (Hungary); Tárkányi, F.; Takács, S. [Institute for Nuclear Research, Hungarian Academy of Sciences (ATOMKI), Debrecen (Hungary); Hermanne, A. [Cyclotron Laboratory, Vrije Universiteit Brussel (VUB), Brussels (Belgium); Yamazaki, H.; Baba, M.; Mohammadi, A. [Cyclotron Radioisotope Center (CYRIC) Tohoku University, Sendai (Japan)

    2013-08-01

    Highlights: •Experimental excitation function of proton induced reactions on manganese up to 70 MeV. •Model code calculations with EMPIRE-3 and TALYS (TENDL-2012). •Integral production yield calculation. •Thin Layer Activation (TLA) curves for {sup 54}Mn and {sup 51}Cr. •Tabulated experimental results. -- Abstract: In the frame of a systematic study of the activation cross-sections of the proton induced nuclear reactions, excitation functions of the {sup 55}Mn(p,x){sup 54,52g}Mn, {sup 51}Cr and {sup 48}V were measured up to 70 MeV. Cross-sections were measured with the activation method using the stacked foil irradiation technique and high resolution γ-ray spectrometry. The experimental data are analyzed and compared to the earlier results and to the prediction of the EMPIRE-3 as well as the TALYS theoretical model code in the TENDL-2012 library. From the measured cross-section data integral production yields were calculated. Practical applications of the cross-sections e.g. for thin layer activation are discussed.

  19. [Study of age and sex dependance in renal clearances with radioisotopes (author's transl)].

    Science.gov (United States)

    Schernthaner, G; Erd, W; Ludwig, H; Sinzinger, H; Höfer, R

    1976-03-01

    In 85 patients between 15 and 95 years of age (40 male patients and 45 females) without any signs of renal disease (concentration of serum creatinine below 1,4 mg/100ml, normal diastolic blood pressure and normal urine analysis) a highly significant negative correlation was found between glomerular filtration rate (GFR, determined by 51Cr-EDTA - slope-clearance) and renal plasma flow (RPF, determined by 131J-oJHS-iodinehippuricacid-totalclearance) on one side and age on the other. Beginning with a basic value of 160