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Sample records for 177lu 51cr 153sm

  1. Determination of human absorbed dose of cocktail of 153Sm/177Lu-EDTMP, based on biodistribution data in rats

    International Nuclear Information System (INIS)

    The aim of this work was to estimate the absorbed dose due to compositional radiopharmaceutical of 153Sm/177Lu-EDTMP in human organs based on biodistribution data of rats by using OLINDA/EXM software. The absorbed dose was determined by the Radiation Dose Assessment Resource (RADAR) formulation after calculating cumulated activities in each organ. The results show that the organs that received the highest absorbed dose were the bone surface and red marrow (1.51 and 7.99 mGy/ MBq for 153Sm, and 1.98 and 10.76 mGy/MBq for 177Lu, respectively). According to the results, using of cocktail of 153Sm/177Lu-EDTMP has considerable characteristics as compared to 153Sm-EDTMP and 177Lu-EDTMP alone. (author)

  2. Organ doses from hepatic radioembolization with 90Y, 153Sm, 166Ho and 177Lu: A Monte Carlo simulation study using Geant4

    Science.gov (United States)

    Hashikin, N. A. A.; Yeong, C. H.; Guatelli, S.; Abdullah, B. J. J.; Ng, K. H.; Malaroda, A.; Rosenfeld, A. B.; Perkins, A. C.

    2016-03-01

    90Y-radioembolization is a palliative treatment for liver cancer. 90Y decays via beta emission, making imaging difficult due to absence of gamma radiation. Since post-procedure imaging is crucial, several theranostic radionuclides have been explored as alternatives. However, exposures to gamma radiation throughout the treatment caused concern for the organs near the liver. Geant4 Monte Carlo simulation using MIRD Pamphlet 5 reference phantom was carried out. A spherical tumour with 4.3cm radius was modelled within the liver. 1.82GBq of 90Y sources were isotropically distributed within the tumour, with no extrahepatic shunting. The simulation was repeated with 153Sm, 166Ho and 177Lu. The estimated tumour doses for all radionuclides were 262.9Gy. Tumour dose equivalent to 1.82GBq 90Y can be achieved with 8.32, 5.83, and 4.44GBq for 153Sm, 166Ho and 177Lu, respectively. Normal liver doses by the other radionuclides were lower than 90Y, hence beneficial for normal tissue sparing. The organ doses from 153Sm and 177Lu were relatively higher due to higher gamma energy, but were still well below 1Gy. 166Ho, 177Lu and 153Sm offer useful gamma emission for post-procedure imaging. They show potential as 90Y substitutes, delivering comparable tumour doses, lower normal liver doses and other organs doses far below the tolerance limit.

  3. A comparative study of preliminary dosimetry for human based on distribution data in rats with 111In, 90Y, 153Sm, and 177Lu labeled rituximab

    Directory of Open Access Journals (Sweden)

    Radfar Edalat

    2012-01-01

    Full Text Available Radio immunotherapy is one of the most important and effective therapies for B-cell non Hoddgkin’s lymphoma treatment. Today, anti CD-20 antibodies labeled with beta emitter radionuclides are used in radio immunotherapy. Various radionuclides for labeling anti CD-20 antibodies have been studied and developed for the treatment and diagnosis of malignancies. This paper describes the preparation, bio-distribution and absorbed dose rate of 111In, 90Y, 177Lu, and 153Sm labeled anti CD-20 antibodies (rituximab in human organs, after injection to rats. The macro cyclic bifunctional chelating agent, N-succinimidyl-1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA-NHS for conjugation to antibody, was used to prepare DOTA-rituximab. The conjugates were purified by molecular filtration, the average number of DOTA conjugated per mAb was calculated and total concentration was determined by spectrophotometric method. Radio-labeling was performed at 40 °C for 24 hours. After the quality control studies, the final radioactive solution was injected intravenously into rats through their tail vein. The tissue uptakes of each injection were measured. Then we calculated S values for 177Lu and 153Sm by using specific absorbed fractions and data used in the manner of radio-labeled analysis and dosimetry for humans. The absorbed dose rate of each organ was calculated in the specific time by medical internal radiation dose method with linear approximation in the activity measurements.

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

    International Nuclear Information System (INIS)

    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 177Lu-DOTMP and 153Sm-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 177Lu-DOTMP and 153Sm-DOTMP complexes. The agents were prepared by dissolving the lyophilized powder in 1 mL of normal saline and incubating with 177LuCl3 or 153SmCl3, 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 177Lu-DOTMP and 153Sm-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 177Lu-DOTMP and 153Sm-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.

  5. 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.

  6. Absorbed dose assessment of 177Lu-zoledronate and 177Lu-EDTMP for human based on biodistribution data in rats

    OpenAIRE

    Yousefnia, Hassan; Zolghadri, Samaneh; Jalilian, Amir Reza

    2015-01-01

    Over the past few decades, several bone-seeking radiopharmaceuticals including various bisphosphonate ligands and β-emitting radionuclides have been developed for bone pain palliation. Recently, 177Lu was successfully labeled with zoledronic acid (177Lu-ZLD) as a new generation potential bisphosphonate and demonstrated significant accumulation in bone tissue. In this work, the absorbed dose to each organ of human for 177Lu-ZLD and 177Lu-ethylenediaminetetramethylene phosphonic acid (177Lu-EDT...

  7. Production of 177Lu for targeted radionuclide therapy: Available options

    International Nuclear Information System (INIS)

    This review provides a comprehensive summary of the production of 177Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of 177Lu having the required quality for preparation of a variety of 177Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 177Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. While both “direct” and “indirect” reactor production routes offer the possibility for sustainable 177Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. A broad understanding and discussion of the issues associated with 177Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177Lu-labeled radiopharmaceuticals, but also help future developments

  8. Preparation and biological assessment of 177Lu-BPAMD as a high potential agent for bone pain palliation therapy. Comparison with 177Lu-EDTMP

    International Nuclear Information System (INIS)

    In this study, 177Lu-(4-{[(bis(phosphonomethyl))- carbamoyl]methyl}-7,10-bis(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl) acetic acid (177Lu-BPAMD) was successfully prepared. The quality control, partition coefficient, hydroxyapatite binding assay and stability of the complex were determined. For better comparison, biodistribution patterns of 177Lu-BPAMD and 177Lu-EDTMP complexes were compared in same animal model. 177Lu-BPAMD was prepared with high radiochemical purity ([93 %) and specific activity of 534 GBq/mmol at the optimal conditions. Comparative study between 177Lu-BPAMD and 177Lu-EDTMP indicated higher bone uptake and lesser accumulation in the other organs for 177Lu-BPAMD. 177Lu-BPAMD can be considered as a promising agent for bone pain palliation in the near future. (author)

  9. Comparison of [177Lu-DOTA0,Tyr3]octreotate and [177Lu-DOTA0,Tyr3]octreotide: which peptide is preferable for PRRT?

    International Nuclear Information System (INIS)

    Patients with somatostatin receptor subtype 2-positive metastasised neuroendocrine tumours can be treated with [177Lu-DOTA0,Tyr3]octreotate. Some use octreotide as the peptide for peptide receptor radionuclide therapy (PRRT). We compared in seven patients [177Lu-DOTA0,Tyr3]octreotide (177Lu-DOTATOC) and [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE), to see which peptide should be preferred for PRRT with 177Lu. In the same patients, 3,700 MBq 177Lu-DOTATOC and 3,700 MBq 177Lu-DOTATATE was administered in separate therapy sessions. Amino acids were co-administered. Whole-body scanning was performed on days 1, 4 and 7 post therapy. Blood and urine samples were collected. We calculated residence times for tumours, spleen and kidneys. All patients had longer residence times in spleen, kidneys and tumours after use of 177Lu-DOTATATE (p=0.016 in each case). Comparing 177Lu-DOTATATE with 177Lu-DOTATOC, the mean residence time ratio was 2.1 for tumour, 1.5 for spleen and 1.4 for kidneys. Dose-limiting factors for PRRT are bone marrow and/or kidney dose. Although the residence time for kidneys was longer when using 177Lu-DOTATATE, the mean administered dose to tumours would still be advantageous by a factor of 1.5, assuming a fixed maximum kidney dose is reached. Plasma radioactivity after 177Lu-DOTATATE was comparable to that after 177Lu-DOTATOC. Urinary excretion of radioactivity was comparable during the first 6 h; thereafter there was a significant advantage for 177Lu-DOTATOC. 177Lu-DOTATATE had a longer tumour residence time than 177Lu-DOTATOC. Despite a longer residence time in kidneys after 177Lu-DOTATATE, tumour dose will always be higher. Therefore, we conclude that the better peptide for PRRT is octreotate. (orig.)

  10. Report on the 1. research coordination meeting on 'Development of therapeutic radiopharmaceuticals based on 177Lu for radionuclide therapy'

    International Nuclear Information System (INIS)

    from the production site. Patients suffering from breast, lung and prostate cancer develop metastasis in bone in the advanced stage of their diseases and therapeutic radiopharmaceuticals such as 153Sm-EDTMP and 89SrCl2 are used effectively for pain palliation due to skeletal metastases. Despite the fact that the above bone pain palliating agents give good clinical results; their wider use has met with practical difficulties. Though 153Sm can be prepared in adequate quantities in medium flux reactors, its short half life (47 h) is the major disadvantage. It is essential to handle large quantities of activity to compensate for decay losses, during production and delivery of the radiopharmaceutical. In the case of 89Sr, there is very limited capacity for production due to the very low cross section making this product expensive and unaffordable for many patients. It is expected that a 177Lu based bone palliating agent will offer the same clinical efficacy without the disadvantages mentioned above. Currently there is good published data available on the production of 177Lu and the preparation of phosphonates based radiopharmaceuticals which show high bone uptake. 177Lu produced in the low to medium flux research reactors available in the MS can be used for bone pain palliation. High specific activity 177Lu that is prepared in high flux research reactors is needed for radiolabelling antibodies and peptides. These antibodies introduced to patients alone or in conjunction with 90Y products are showing promising results in clinical trials. Large quantities of high specific activity 177Lu can be prepared by irradiating enriched targets in high flux research reactors and hence, in the long term the cost of high specific activity 177Lu should come down to reasonable levels. The wider availability of 177Lu will make it feasible for the production of therapeutic radiopharmaceuticals with lower cost ensuring higher availability in MS. The CRP 'Development of Therapeutic

  11. radiolabeling of DOTA-substance P with 177Lu and biodistribution of 177Lu-DOTA-substance P

    International Nuclear Information System (INIS)

    The aim of this project is to evaluate the biodistribution of 177Lu-DOTA-SP in normal mice and in PANC-1 tumor bearing nude mice and to pave the way for its potentially medical application. In this study, 177Lu-DOTA-SP was successfully prepared with labeling yield of greater than 90% at optimized conditions and more than 98% of radiochemical purity after C18 Sep-Pak purification. 177Lu-DOTA-SP showed good stability in saline and in 5% serum while it decomposed slowly in 10% serum. Biodistribution studies in normal mice showed high uptake of 177Lu-DOTA-SP in the kidneys, indicating the excretion mainly by renal pathway. In addition, 177Lu-DOTA-SP was washed out from the blood quickly. Bio- distribution of 177Lu-DOTA-SP in PANC-1 tumor bearing mice showed higher uptake in pancreatic tumor than that in normal pancreas, indicating the presence of NK-1 receptors in PANC-1 pancreatic tumor. However, from SPECT image, no radioactivity accumulation was observed in PANC-1 tumor. Further evaluation is needed to confirm its potential application for radiotherapy of pancreatic cancers. (authors)

  12. Preparation and quality control of {sup 153}Sm radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Swasono, R. Tamat; Widyastuti, W.; Purwadi, B.; Laksmi, I. [Radioisotope Production Center - BATAN, Jakarta (Indonesia)

    1998-10-01

    The paper summarizes the preparation and quality control of {sup 153}Sm-EDTMP and three {sup 153}Sm-radiosynovectomy agents. Natural and enriched Sm{sub 2}O{sub 3} (98.7% {sup 152}Sm) irradiated in RSG-GAS 30 MW reactor yielded pure and high specific activity {sup 153}Sm. Labeling of EDTMP with {sup 153}Sm was carried out by mixing {sup 153}SmCl{sub 3} solution of pH 4.0 to an EDTMP solution at room temperature then pH adjustment to 8. The {sup 153}Sm-EDTMP complex was separated from the free {sup 153}Sm{sup +3} on a Chelex 100 column. Radiochemical purity was determined by thin layer chromatography using Cellulose sheets and pyridine: ethanol: water (1: 2: 4) mixture as solvent. The {sup 153}Sm-EDTMP has been shown to be stable for two weeks. Three particulate preparations of {sup 153}Sm used for the irradiation of chronic synovitis have been studied. They are hydroxyapatite particles, human serum albumin microspheres and ferric hydroxide macroaggregates. The {sup 153}Sm-ferric hydroxide macroaggregates were prepared in a single step by coprecipitation of {sup 153}Sm in the formation of Fe(OH){sub 3}. Preparation of {sup 153}Sm-labelled hydroxyapatite particles and {sup 153}Sm-labelled albumin microspheres were carried out by {sup 153}Sm labelling of previously prepared particles. Radiolabelling efficiency were greater than 95% for hydroxyapatite particles and macroaggregates and was lower than 20% for albumin microspheres. The particle sizes were inspected using an optical microscope with a haemocytometer and micrometric ocular. (author)

  13. 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

  14. 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)

  15. Biodistribution and Dosimetry of 177Lu-tetulomab, a New Radioimmunoconjugate for Treatment of Non-Hodgkin Lymphoma

    OpenAIRE

    Repetto-Llamazares, Ada H. V.; Larsen, Roy H.; Mollatt, Camilla; Lassmann, Michael; Dahle, Jostein

    2013-01-01

    The biodistribution of the anti-CD37 radioimmunoconjugate 177Lu-tetraxetan-tetulomab (177Lu-DOTA-HH1) was evaluated. Biodistribution of 177Lu-tetraxetan-tetulomab was compared with 177Lu-tetraxetan-rituximab and free 177Lu in nude mice implanted with Daudi lymphoma xenografts. The data showed that 177Lu-tetulomab had a relevant stability and tumor targeting properties in the human lymphoma model. The half-life of 177Lu allowed significant tumor to normal tissue ratios to be obtained indicatin...

  16. Studies concerning the preparation of the 153Sm complex with EDTMP (ethylenediaminetetra methylenephosphonic acid) and other 153Sm complexes with other phosphonates, at room temperature

    International Nuclear Information System (INIS)

    This work presents a study on the preparation of the complexes 153Sm - EDTMP, 153Sm - HEDP, 153Sm - NTMP, 153Sm - DTPMP and 153Sm - HDTMP at room temperature. The preparation of the complex 153Sm - HDTMP, under heating (70 - 72 deg C), was also studied. Several factors affecting the 153Sm - EDTMP complexing yields were studied, due to its importance for use in Nuclear Medicine. These factors were: the molar ratio [ligand] / [metal], the ligand concentration and the incubation time of the mixture ligand-metal. The preparation of this complex, in low molar ratios, was also investigated. A study of the 153Sm - EDTMP concerning the 'in vitro' stability, when this complex was prepared in low radioactive concentrations was performed. A study on the temperature influence on its degradation, when this complex was obtained in higher radioactive concentrations, was also performed. The preparation of the complexes 153Sm - HEDP, 153Sm - NTMP, 153Sm - DTPMP and 153Sm - HDTMP was investigated by preparing the complexes in two situations: high molar ratio and ligand concentration and low molar ratio and ligand concentration. The 'in vitro' stability of each complex, obtained in low radioactive concentration was studied. In the specific case of the complex 153Sm - HDTMP, its biological distribution in mice was performed. All the complexes were investigated by high performance liquid chromatography (HPLC) and its complexing yields were determined by other three chromatographic processes: ionic exchange, thin layer chromatography (TLC - SG) and paper chromatography. The chromatographic processes were performed by association with specific radiochemical techniques. This work also presents a comparative study on the chromatograms obtained by thin layer chromatography (TLC - SG) and paper chromatography, when evaluated by the technique of cutting the strips into pieces and the chromatograms performed directly on a radiochromatography. The shape of the chromatograms and Rf values of 153

  17. Production of {sup 177}Lu for targeted radionuclide therapy: Available options

    Energy Technology Data Exchange (ETDEWEB)

    Dah, Ashutosh [Isotope Production and Applications Division, Bhabha Atomic Research Centre (BARC), Mumbai (India); Pillai, Maroor Raghavan Ambikalmajan [Molecular Group of Companies. Kerala (India); Knapp, Furn F. Jr. [Medical Isotopes Program, Isotope Dept. Group, Oak Ridge National Laboratory (ORNL), Oak Ridge (United States)

    2015-06-15

    This review provides a comprehensive summary of the production of {sup 177}Lu to meet expected future research and clinical demands. Availability of options represents the cornerstone for sustainable growth for the routine production of adequate activity levels of {sup 177}Lu having the required quality for preparation of a variety of {sup 177}Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of {sup 177}Lu for use in targeted radionuclide therapy (TRT) dictate that a holistic consideration should evaluate all governing factors that determine its success. While both “direct” and “indirect” reactor production routes offer the possibility for sustainable {sup 177}Lu availability, there are several issues and challenges that must be considered to realize the full potential of these production strategies. This article presents a mini review on the latest developments, current status, key challenges and possibilities for the near future. A broad understanding and discussion of the issues associated with {sup 177}Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of {sup 177}Lu-labeled radiopharmaceuticals, but also help future developments.

  18. [{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.

  19. Photoionization spectroscopy for laser extraction of the radioactive isotope 177Lu

    Science.gov (United States)

    D'yachkov, A. B.; Firsov, V. A.; Gorkunov, A. A.; Labozin, A. V.; Mironov, S. M.; Panchenko, V. Y.; Semenov, A. N.; Shatalova, G. G.; Tsvetkov, G. O.

    2015-12-01

    The hyperfine structure of the 5 d6 s 2 2D3/2 → 5 d6 s6 p 4F5/2 transition of the radioactive isotope 177Lu has been investigated by laser photoionization spectroscopy. Measured spectra permitted the determination of hyperfine magnetic dipole constants and electric quadrupole constants for ground and excited state as well as the isotope shift of the 177Lu isotope. The data obtained were used to confirm the selective photoionization of 177Lu from a neutron-irradiated sample that initially had a natural isotope composition. A concentration for 177Lu of 50 % was achieved, and the photoionization efficiency was estimated as suitable for technological application.

  20. 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

  1. Occupational doses in neuroendocrine tumors by using 177Lu DOTATATE

    International Nuclear Information System (INIS)

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of 177Lu 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 μSv to 450 μSv, 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 μSv/h

  2. On the preparation of a therapeutic dose of 177Lu-labeled DOTA-TATE using indigenously produced 177Lu in medium flux reactor

    International Nuclear Information System (INIS)

    177Lu could be produced with a specific activity of ∼23,000 mCi/mg (850 GBq/mg) by neutron activation using enriched 176Lu (64.3%) target when irradiation was carried out at a thermal neutron flux of 1x1014 n/cm2/s for 21 d. 177Lu-DOTA-TATE could be prepared in high radiochemical yield (∼99%) and adequate stability using the 177Lu produced indigenously. The average level of radionuclidic impurity burden in 177Lu due to 177mLu was found to be 250 nCi of 177mLu/1 mCi of 177Lu (9.25 kBq/37 MBq) at the end of bombardment, which corresponds to 0.025% of the total activity produced. The maximum specific activity achievable via careful optimization of the irradiation parameters was found to be adequate for the preparation of a therapeutic dose of the radiopharmaceutical. The in-house preparation of this agent using 25 μg (17.41 nmole) of DOTA-TATE and indigenously produced 177Lu (0.8 μg, 4.52 nmole), corresponding to peptide/Lu ratio of 3.85 yielded 98.7% complexation. Allowing possibility of decay due to transportation to users, it has been possible to demonstrate that at our end, a single patient dose of 150-200 mCi (5.55-7.40 GBq) can be prepared by using 250-333 μg of DOTA-TATE conjugate. This amount compares well with 177Lu-DOTA-TATE prepared for a typical peptide receptor radionuclide therapy (PRRT) procedure which makes use of 100 μg of the DOTA-TATE conjugate, which incorporates 50 mCi (1.85 GBq) of 177Lu activity, thereby implying that in order to achieve a single patient dose of 150-200 mCi (5.55-7.40 GBq), 300-400 μg of the conjugate needs to be used

  3. DOTA-Tyr3-octreotate labelled with 177Lu and 131I. A comparative evaluation

    International Nuclear Information System (INIS)

    The chemical structure of somatostatin receptor ligand 1,4,7,10-tetraazacyclododecane- N,N',N',N'''-tetraacetic acid-Tyr3-octreotate (DOTA-Tyr3-TATE), provides the means for radiolabelling with halogen, by electrophilic substitution, to the Tyr3 residue and with metal, by a coordination mechanism, to the DOTA chelator. In this study, the DOTA-Tyr3-TATE was radiolabelled with 177Lu and 131I of high radiochemical purity and specific activity. The in vitro study regarding the competitive and the saturation binding assays were performed using rat brain cortex membrane. The IC50 value was determined as 4.74nM for natLu-DOTA-Tyr3-TATE and the Kd value was 142.8pM for 177Lu-DOTA-Tyr3-TATE. The biodistribution data of 177Lu-DOTA-Tyr3-TATE and DOTA-131I-Tyr3-TATE in HRS1 (hepato-colangiom carcinomas) tumour bearing rats, show that the 177Lu-DOTA-Tyr3-TATE is more stable and has better uptake than DOTA-131I-Tyr3-TATE. Furthermore, the competitive localization index of 177Lu- DOTA-Tyr3-TATE is three times higher than that obtained for DOTA-131I -Tyr3-TATE. The results of work based on comparative experiments suggest that 177Lu-DOTA-Tyr3- TATE could be an effective targeted radiotherapy agent of SSTR tumours. (author)

  4. 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)

  5. Preparation, QC and biological evaluation of 177Lu-DOTA-Tyr3- Octreotate

    International Nuclear Information System (INIS)

    Somatostatin (SS) plays a major role in the physiological regulation of hormones and organs. Radiolabelled somatostatin analogues have been studied for targeted radiotherapy of neuroendocrine tumors and with other malignancies known to bear somatostatin receptor, such as lymphoma, breast cancer, small-cell lung cancer and melanoma. Reactor produced 177Lu is emerging as an important radionuclide for cancer therapy since it decays with half-life of 6.71d by the emission of β- particles with Eβ of 498 keV (78.6), 384 keV (9.1%) and 176 keV (12.2) to stable 177Hf. The 177Lu radionuclide has tissue mean range of 670 μm is considered to be more effective for the treatment of small tumour. High specific activity 177Lu radionuclide (> 8Ci/mg) prepared in our laboratory is considered to be appropriate for labelling peptides. Several experiments for obtaining optimum labelling yield of 177Lu-DOTA-Tyr3-Octreotate under different reaction parameters such pH, incubation time and reaction temperature were performed. Radiochemical purity of 177Lu-DOTA-Tyr3- Octreotate was determined by radio-TLC with C18 plates developed in 70:30 MeOH:10% NH4OAc. Under these conditions 177Lu-DOTA-Tyr3-Octreotate appears at Rf 0.8 while 177Lu-acetate stays at the Rf 0. High labelling yield (>98%) of 177Lu-DOTA-Tyr3-Octreotate was obtained at pH 4.5 at a temperature of 90 deg. C for 30 minutes incubation time. The 177Lu-DOTA-Tyr3-Octreotate was further investigated for stability in acetate/ascorbate buffer and saline at room temperature (12.15 deg. C). The data showed that the labelled complex was stable in buffer and saline medium for a period >24 hours. Animal study of 177Lu-DOTA-Tyr3-Octreotate was performed in ∼200 g male Sprague Dawley rats. Two hundred microlitres of the labelled (80 μCi) were injected into the tail veins of rats and each rat was killed at 1 hour, 2 hours, 6 hours, 12 hours, 24 hours and 72 hours. Countings were performed using Capintec dose calibrator. The

  6. Preparation of 177Lu-DOTA/DTPA-Bz-Cys-RGD dimer and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    177Lu-DOTA-Bz-Cys-RGD dimer and 177Lu-DTPA-Bz-Cys-RGD dimer were prepared, and the in vitro and in vivo properties were compared. TLC and HPLC show that the labeling yields of two radiolabeled compounds are more than 95% under optimal conditions (pH=5.0, reacting at 100 degree C for 15-20 min), and the two radiolabeled compounds show pretty good in vitro stability. HPLC analyses and lg P values reveal that lipophilicity of 177Lu-DOTA-Bz-Cys- RGD dimer is higher than 177Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177Lu-DOTA-Bz-Cys-RGD dimer is much better than 177Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177Lu labeling of RGD dimer. (authors)

  7. 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.

  8. Investigation of 177Lu-folate based radionuclide tumor therapy in combination with pemetrexed

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: The antifolate pemetrexed (PMX) was shown to improve the tissue distribution profile of radio-folates by reducing undesired renal accumulation without affecting uptake in the tumor. We hypothesized that PMX would have a dual role in combination with therapeutic radio-folates as it may protect kidneys from radio-nephrotoxicity and contribute to the anticancer effect as a chemotherapeutic and/or radiosensitizing agent. Therefore, the aim of the study was to investigate the combined application of 177Lu-folate and PMX in vitro an in vivo. Material and Methods: The DOTA-folate conjugate (EC0800, Endocyte Inc.) was labeled with 177Lu at high specific activity. In vitro the effects of 177Lu-EC0800 alone and in combination with PMX was tested with FR-positive KB tumor cells using MTT and clonogenic assays. In vivo, undesired effects of 177Lu-EC0800 (20 MBq/mouse) with/without co-application of PMX were investigated in non-tumor bearing mice over six months. Kidney function was monitored by the determination of renal accumulation of 99mTc-DMSA using SPECT. Therapy studies in KB tumor-bearing mice were performed with 177Lu-EC0800 (20 MBq) combined with subtherapeutic (0.4 mg) and therapeutic amounts (1.6 mg) of PMX. Results: Determination of the combination index revealed a synergistic inhibitory effect of 177Lu-EC0800 and PMX on the viability of both FR-positive cancer cell lines in vitro (CI < 0.8). In vivo application of 20 MBq 177Lu-EC0800 impaired kidney function 6 months as demonstrated by a significantly reduced renal uptake of 99mTc-DMSA and elevated plasma levels of blood urea nitrogen. Pre-injection of subtherapeutic amounts of PMX (0.4 mg) protected kidneys effectively as demonstrated by parameters which were in the same range as those of untreated control animals. Therapy studies revealed a 3-fold more pronounced anticancer effect and 25% increased survival if 177Lu-EC0800 was combined with therapeutic amounts of PMX

  9. 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.

  10. Preparation and evaluation of 177Lu-DOTA-Bz-RGD dimer and 177Lu-DOTA-Bz-PEG4-RGD dimer

    International Nuclear Information System (INIS)

    177Lu-DOTA-Bz-RGD dimer and 177Lu-DOTA-Bz-PEG4-RGD dimer were pre- pared, and the effect of PEG4 on labeling conditions and in vitro stability as well as pharma-cokinetic properties and biodistribution in normal mice for the radiolebeled compounds was compared. The results of TLC and HPLC show that the labeling yield of two radiolabeled compounds was more than 95% under optimal conditions (pH 4.0 and pH 6.0, respectively, reacting at 100 degree C for 15-20 min). The two radiolabeled compounds show pretty good stability in saline. HPLC analyses and lgPow values revealed that introducing of PEG4 increased the lipophilic character of radiolabeled compounds, but had no significant changes on pharmacokinetic properties and biodistribution in normal mice. (authors)

  11. Development of a therapeutic radiopharmaceutical 177Lu-DOTA- Minigastrin for potential use in PRRT

    International Nuclear Information System (INIS)

    The aim of this work is to obtain 177Lu-DOTA-Minigastrin with high radiochemical purity (RP) and the highest specific activity (Ae) as possible, using a locally produced (Nuclear Reactor RA-3, Ezeiza Atomic Center) 177LuCl3 of an intermediate level of Ae (between 6.36 to 17.95 Ci/mg of 176Lu) ) and also to perform in vitro and in vivo stability tests, dose calculation in normal mice and its extrapolation to a human model. (authors)

  12. The addition of DTPA to [177Lu-DOTA0,Tyr3]octreotate prior to administration reduces rat skeleton uptake of radioactivity

    International Nuclear Information System (INIS)

    Peptide receptor-targeted radionuclide therapy is nowadays also being performed with DOTA-conjugated peptides, such as [DOTA0,Tyr3]octreotate, labelled with radionuclides like 177Lu. The incorporation of 177Lu is typically ≥99.5%; however, since a total patient dose can be as high as 800 mCi, the amount of free 177Lu3+ (= non-DOTA-incorporated) can be substantial. Free 177Lu3+ accumulates in bone with unwanted irradiation of bone marrow as a consequence. 177Lu-DTPA is reported to be stable in serum in vitro, and in vivo it has rapid renal excretion. Transforming free Lu3+ to Lu-DTPA might reroute this fraction from accumulation in bone to renal clearance. We therefore investigated: (a) the biodistribution in rats of 177LuCl3, [177Lu-DOTA0,Tyr3]octreotate and 177Lu-DTPA; (b) the possibilities of complexing the free 177Lu3+ in [177Lu-DOTA0,Tyr3]octreotate to 177Lu-DTPA prior to intravenous injection; and (c) the effects of free 177Lu3+ in [177Lu-DOTA0,Tyr3]octreotate, in the presence and absence of DTPA, on the biodistribution in rats. 177LuCl3 had high skeletal uptake (i.e. 5% ID per gram femur, with localization mainly in the epiphyseal plates) and a 24-h total body retention of 80% injected dose (ID). [177Lu-DOTA0,Tyr3]octreotate had high and specific uptake in somatostatin receptor-positive tissues, and 24-h total body retention of 19% ID. 177Lu-DTPA had rapid renal clearance, and 24-h total body retention of 4% ID. Free 177Lu3+ in [177Lu-DOTA0,Tyr3]octreotate could be complexed to 177Lu-DTPA. Accumulation of 177Lu in femur, blood, liver and spleen showed a dose relation to the amount of free 177Lu3+, while these accumulations could be normalized by the addition of DTPA. After labelling [DOTA0,Tyr3]octreotate with 177Lu the addition of DTPA prior to intravenous administration of [177Lu-DOTA0,Tyr3]octreotate is strongly recommended. (orig.)

  13. Improving quantitative dosimetry in (177)Lu-DOTATATE SPECT by energy window-based scatter corrections

    DEFF Research Database (Denmark)

    de Nijs, Robin; Lagerburg, Vera; Klausen, Thomas L;

    2014-01-01

    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...

  14. Studies on apoptosis in bone tumor cells induced by 153Sm

    Institute of Scientific and Technical Information of China (English)

    ZHU Shou-Peng; XIAO Dong; HAN Xiao-Feng

    2004-01-01

    The apoptosis in human bone tumor cells induced by internal irradiation with 153Sm was studied. The morphological changes in bone tumor cells were observed by electronic and fluorescent microscopy, as well as DNA agarose gel eletrophoresis. DNA chain fragmentation, microautoradiographic tracing and the inhibition rate of proliferation in bone tumor cells exposed to 153Sm with different duration time were examined. It was demonstrated that the bone tumor cells exposed to 153Sm displayed nuclear fragmentation, pyknosis, margination of condensed chromatin, and formation of membrane bounded apoptotic bodies, whereas the percentage of DNA chain fragmentation of bone tumor cells increases in direct proportion to the duration of irradiation with 153Sm, as well as DNA ladder formation in apoptotic cells. Also a marked inhibition effect of proliferation in bone tumor cells after exposure with 153Sm was observed.

  15. Safety and feasibility of percutaneous vertebroplasty with radioactive {sup 153}Sm PMMA in an animal model

    Energy Technology Data Exchange (ETDEWEB)

    Lu Jun [Department of Radiotherapy, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi' an 710032, Shaanxi Province (China); Deng Jinglan, E-mail: dengjinglan@gmail.com [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi' an 710032, Shaanxi Province (China); Zhao Haitao [Department of Radiology, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi' an 710032, Shaanxi Province (China); Shi Mei [Department of Radiotherapy, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi' an 710032, Shaanxi Province (China); Wang Jing [Department of Nuclear Medicine, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi' an 710032, Shaanxi Province (China); Zhao Lina [Department of Radiotherapy, Xijing Hospital, Fourth Military Medical University, 15 West Changle Road, Xi' an 710032, Shaanxi Province (China)

    2011-05-15

    Purpose: We investigated the safety and feasibility of the combination of samarium-153-ethylenediamine tetramethylene phosphonate ({sup 153}Sm-EDTMP)-incorporated bone cement (BC) with percutaneous vertebroplasty (PVP) in dogs. Methods and materials: {sup 153}Sm-EDTMP-incorporated BC was prepared by combining solid {sup 153}Sm-EDTMP and polymethylmethacrylate (PMMA) immediately before PVP. It was then injected into the vertebrae of four healthy mongrel dogs (two males and two females) by PVP under CT guidance. Each dog was subjected to five PVP sessions at a {sup 153}Sm-EDTMP dose of 30-70 mCi. The suppressive effect of local injection of {sup 153}Sm-EDTMP on the hematopoietic system was evaluated through counting of peripheral blood cells. Distribution of {sup 153}Sm-EDTMP-incorporated BC and the status of tissues adjacent to injected vertebrae were evaluated with SPECT, CT and MRI. Histopathology was carried out to assess the influence of PVP on the vertebra and adjacent tissues at the microscopic level. Results: PVP was done successfully, and all dogs exhibited normal behavior and stable physical signs after procedures. {sup 153}Sm-EDTMP-incorporated BC was concentrated mainly in target vertebrae, and the peripheral blood cells remained within normal range. The spinal cord and tissues around BC did not exhibit signs of injury even when the dosage of {sup 153}Sm-EDTMP increased from 30 mCi to 70 mCi. Conclusion: A dose lower than 70 mCi of {sup 153}Sm is safe when it was injected into vertebrae. {sup 153}Sm-EDTMP-incorporated BC did not influence the effect of PVP. This means might strengthen anti-tumor activity locally for vertebra with osseous metastasis without damaging adjacent tissues.

  16. Preparation and animal imaging of 153Sm-EDTMP as a bone seeking radiopharmaceutical

    International Nuclear Information System (INIS)

    Ethylenediamine- tetra methylenephosphonic acid (EDTMP) has widely used chelator for the labeling of bone seeking radiopharmaceuticals complexed with radio metals. 153Sm can be produced by the HANARO reactor at the Korea Atomic Energy Research Institute, Taejon, Korea. 153Sm has favourable radiation characteristics T1/2=46.7 h, β max=0.81 MeV (20%), 0.71 MeV (49%), 0.64 MeV (30%) and γ=103 keV (30%) emission which is suitable for imaging purposes during therapy. We investigated the labeling condition of 153Sm-Emptied and imaging of 153Sm-EDTMP in normal rats. EDTMP 20 mg was solved in 0.1 mL 2 M NaOH. 153SmCl3 was added to EDTMP solution and pH of the reaction mixtures was adjusted to 8 and 12, respectively. Radiochemical purity was determined with paper chromatography. After 30 min. reaction, reaction mixtures were neutralized to pH 7.4 and the stability was estimated upto 120 hrs. Imaging studies of each reaction were performed in normal rats (37 MBq/0.1 mL). The labeling yield of 153Sm-EDTMP was 99%. The stability of pH 8 reaction at 60, 96 and 120 hr was 99%,95%,89% and that of pH 12 at 36, 60, 96, and 120 hr was 99%, 95%, 88%, 66%, respectively. The 153Sm-EDTMP showed constantly higher bone uptake from 2 to 48 hr after injection. 153Sm-EDTMP, labeled at pH 8 reaction condition, has been stably maintained. Image of 153Sm-EDTMP at 2, 24, 48 hr after injection, demonstrate that 153Sm-EDTMP is a good bone seeking radiopharmaceuticals

  17. Cytogenetic analysis of 153 Sm-EDTMP in peripheral lymphocytes from patients with bone cancer metastasis

    International Nuclear Information System (INIS)

    The 153 Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of 153 Sm-EDTMP at cellular level. The present study was conducted with the aim of evaluating the cytogenetic effects of 153 Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique. For that, the blood samples were collected before and one hour after the endovenous administrations of 153 Sm-EDTMP (mean activity of 42.53 ± 5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before153 Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with 153 Sm-EDTMP, did not influence these parameters. The obtained data showed that the therapy with 153 Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes one hour after its administration in patients, although, theoretically, a long term stochastic effect cannot be disregarded. (author)

  18. Optimization of the production, quality control of samarium-153, 153 Sm-EDTMP and biodistribution of 153 Sm-EDTMP in animals for metastatic bone cancer pain palliation

    International Nuclear Information System (INIS)

    Samarium-153 has suitable physical properties for metastatic bone cancer pain palliation with 46.7 hr half-life. Not only decays it with multi-energetic B-radiation but also emits a gamma-ray at 103 keV which is suitable for imaging during therapy. The optimization of 153 Sm production, by irradiation 152 Sm2 O3 as a solid and liquid target, is conducted in TRIGA Mark III research reactor. The feasibility to label it with EDTMP, a bone seeking agent, is also studied. The specific activity obtained from liquid target is about 2 times higher than solid target. At least 500 mCi/week can be produced with specific activity about 50 to 70 mCi/mg Sm. EDTMP as Na-EDTMP and Ca-EDTMP is labelled with 153 Sm at various conditions. The radiochemical purity achieved, is greater than 99% (85 mCi of 153 Sm labelled with Na-EDTMP or Ca-EDTMP, molar ratio of Sm:EDTMP 1:10 and 1:100 respectively, pH 7.5-8). The biodistribution in animals of 153 Sm-Na-EDTMP showed similar results as obtained from 153 Sm-Ca-EDTMP but slightly higher uptake in various organs and showed high skeletal uptake up to 32% at 24 hr post injection. The labeled compound obviously undergoes rapid removal, completely clearance into urine within 24 hr. This labeled compound is under clinical trials

  19. Urine management after treatment with ''153 Sm-EDTMP (QUADRAMET)

    International Nuclear Information System (INIS)

    The main purpose was to establish and to evaluate a new protocol of individualized treatment of patient urine after ''153 Sm-EDTMP injection, with a more efficient management of the wastes. Excreted urine was collected in an appropriate container form which, previous to sealing it, an aliquot of 10 ml was obtained. Experimental half-life (t1/2) of the isotope was then determined by measuring the activity at different times, besides the minimum time necessary for disposing of the radioactive wastes as regular trash. The measured half-life adjusted well to the theoretical value of the isotope. The time of considered storage oscillated between 19 and 26 days, based on the activity excreted by each patient. The main idea is the consideration of the set container-urine as solid waste: the evaluation of the minimum storage time necessary to its elimination is made in terms of legal limitation of specific activity by mass unit. The immediate advantages ares: the elimination of disagreeable scents by the storage of urine, it is not necessary a liquid waste disposal to eliminate it, and a more accurate knowledge of the specific activity at the moment of the elimination (dilution factor is not used). (Author) 10 refs

  20. 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.

  1. Stability and Biodistribution of Thiol-Functionalized and (177)Lu-Labeled Metal Chelating Polymers Bound to Gold Nanoparticles.

    Science.gov (United States)

    Yook, Simmyung; Lu, Yijie; Jeong, Jenny Jooyoung; Cai, Zhongli; Tong, Lemuel; Alwarda, Ramina; Pignol, Jean-Philippe; Winnik, Mitchell A; Reilly, Raymond M

    2016-04-11

    We are studying a novel radiation nanomedicine approach to treatment of breast cancer using 30 nm gold nanoparticles (AuNP) modified with polyethylene glycol (PEG) metal-chelating polymers (MCP) that incorporate 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators for complexing the β-particle emitter, (177)Lu. Our objective was to compare the stability of AuNP conjugated to MCP via a single thiol [DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a dithiol [DOTA-PEG-lipoic acid (LA)] or multithiol end-group [PEG-pGlu(DOTA)8-LA4] and determine the elimination and biodistribution of these (177)Lu-labeled MCP-AuNP in mice. Stability to aggregation in the presence of thiol-containing dithiothreitol (DTT), l-cysteine or glutathione was assessed and dissociation of (177)Lu-MCP from AuNP in human plasma measured. Elimination of radioactivity from the body of athymic mice and excretion into the urine and feces was measured up to 168 h post-intravenous (i.v.) injection of (177)Lu-MCP-AuNP and normal tissue uptake was determined. ICP-AES was used to quantify Au in the liver and spleen and these were compared to (177)Lu. Our results showed that PEG-pGlu(DOTA)8-LA4-AuNP were more stable to aggregation in vitro than DOTA-PEG-LA-AuNP and both forms of AuNP were more stable to thiol challenge than DOTA-PEG-OPSS-AuNP. PEG-pGlu((177)Lu-DOTA)8-LA4 was the most stable in plasma. Whole body elimination of (177)Lu was most rapid for mice injected with (177)Lu-DOTA-PEG-OPSS-AuNP. Urinary excretion accounted for >90% of eliminated (177)Lu. All (177)Lu-MCP-AuNP accumulated in the liver and spleen. Liver uptake was lowest for PEG-pGlu((177)Lu-DOTA)8-LA4-AuNP but these AuNP exhibited the greatest spleen uptake. There were differences in Au and (177)Lu in the liver for PEG-pGlu((177)Lu-DOTA)8-LA4-AuNP. These differences were not correlated with in vitro stability of the (177)Lu-MCP-AuNP. We conclude that conjugation of AuNP with PEG-pGlu((177)Lu-DOTA)8-LA4 via a multithiol

  2. 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.

  3. [177Lu]-DOTA0-Tyr3-octreotate: A Potential Targeted Radiotherapeutic for the Treatment of Medulloblastoma

    OpenAIRE

    Vaidyanathan, Ganesan; Affleck, Donna J.; Zhao, Xiao-Guang; Keir, Stephen T.; Zalutsky, Michael R.

    2010-01-01

    Medulloblastoma, the most common pediatric brain tumor, is difficult to treat because conventional therapeutic approaches result in significant toxicity to normal central nervous system tissues, compromising quality of life. Given the fact that medulloblastomas express the somatostatin subtype 2 receptor, [177Lu-DOTA0,Tyr3]octreotate ([177Lu]DOTA-TATE) could be a potentially useful targeted radiotherapeutic for the treatment of this malignancy. The current study was undertaken to evaluate thi...

  4. Somatostatin-based radiopeptide therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in neuroendocrine tumours

    International Nuclear Information System (INIS)

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90Y or 177Lu. 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 [90Y-DOTA]-TOC or [177Lu-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 [90Y-DOTA]-TOC and 141 patients underwent 259 cycles of [177Lu-DOTA]-TOC. The median survival after [177Lu-DOTA]-TOC and after [90Y-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 [177Lu-DOTA]-TOC over [90Y-DOTA]-TOC in patients with low tumour uptake, solitary lesions and extra-hepatic lesions. The rate of severe transient haematotoxicities was lower after [177Lu-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 [177Lu-DOTA]-TOC and [90Y-DOTA]-TOC. Furthermore, [177Lu-DOTA]-TOC was less haematotoxic than [90Y-DOTA]-TOC. (orig.)

  5. 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.)

  6. 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

  7. Evaluation of the biological and scanning distribution of hydroxyapatite-153Sm radiotherapeutic agent

    International Nuclear Information System (INIS)

    Fixation of 153Sm labeled hydroxyapatite (HA) in the synovial capsule and extra articular localization were evaluated by means of biological distribution tests and gamma scanning studies. These were carried out using HA-153Sm with particle size ranging between 5 and μm, and radiochemical purity above 99%. Animal models used were wistar rats and new zealand rabbits. Rabbits were injected with 7,4 MBq of HA-153Sm while rats received between 1,85 and 92,6 MBq of HA-153Sm. In both cases injection was given in the intra articular area. After injection, scanning images were obtained in rabbits on the 1st, 3rd and 7st day and in rats on the 2nd and 7th day. Biological distribution studies are conducted in the 2 hours to 9 days range in rats and one the 7th day in rabbits. No extra articular localization of HA-153Sm was found in scanning conducted on rabbits by the 1st, 3rd and 7st day after injection, neither on rats by the 2nd and 7th day. Biological distributions for rabbits and rats show localization above 99% in the intra articular area, during the evaluated periods of time. The evaluations of the biological distribution and the scintigraphic images show that fixation of HA-153Sm in the synovial capsule up to the 9th day is very high

  8. Comparative biodistributions and dosimetry of [177Lu]DOTA-anti-bcl-2-PNA-Tyr3-octreotate and [177Lu]DOTA-Tyr3-octreotate in a mouse model of B-cell lymphoma/leukemia

    International Nuclear Information System (INIS)

    Introduction: The B-cell lymphoma/leukemia-2 (bcl-2) proto-oncogene in non-Hodgkin’s lymphoma (NHL) is a dominant inhibitor of apoptosis. We developed a 177Lu-labeled bcl-2 antisense peptide nucleic acid (PNA)–peptide conjugate designed for dual modality NHL therapy, consisting of a radiopharmaceutical capable of simultaneously down-regulating apoptotic resistance and delivering cytotoxic internally emitted radiation. Methods: DOTA-anti-bcl-2-Tyr3-octreotate was synthesized, labeled with 177Lu, and purified using RP-HPLC. The PNA–peptide conjugate was evaluated in Mec-1 NHL-bearing mice and compared to [177Lu]DOTA-Tyr3-octreotate in biodistribution and excretion studies. These data were then used to generate in vivo dosimetry models. Results: The PNA–peptide conjugate was readily prepared and radiolabeled in high yield and radiochemical purity. An in vivo blocking study determined that administration of 50 μg of non-radioactive PNA–peptide was the optimal mass for maximum delivery to the tumor. Based on that result, a dosing regimen of 177Lu-PNA–peptide, for radiologic effect, followed by the optimal mass of non-radioactive compound, for antisense effect, was designed. Using that dosing regimen, biodistribution of the PNA–peptide showed uptake in the tumor with minimal washout over a 4-day period. Uptakes in receptor-positive normal organs were low and displayed nearly complete washout by 24 h. Dosimetry models showed that the tumor absorbed dose of the PNA–peptide conjugate was approximately twice that of the peptide-only conjugate. Conclusions: Biodistribution data showed specific tumor targeting of the 177Lu-labeled PNA–peptide compound with minimal receptor-positive normal tissue uptake when compared to [177Lu]DOTA-Tyr3-octreotate. In vivo dosimetry models predicted a more favorable tumor absorbed dose from [177Lu]DOTA-anti-bcl-2-Tyr3-octreotate

  9. Studies on {sup 177}Lu-labeled methylene diphosphonate as potential bone-seeking radiopharmaceutical for bone pain palliation

    Energy Technology Data Exchange (ETDEWEB)

    Abbasi, Imtiaz Ahmed, E-mail: imtiaz_abbasi@yahoo.co

    2011-04-15

    Objective: {sup 99m}Tc-MDP (technetium-99{sup m}-labeled methylene diphosphonate) has been widely used as a radiopharmaceutical for bone scintigraphy in cases of metastatic bone disease. {sup 177}Lu is presently considered as an excellent radionuclide for developing bone pain palliation agents. No study on preparing a complex of {sup 177}Lu with MDP has been reported yet. Based on these facts, it was hypothesized that a bone-seeking {sup 177}Lu-MDP (lutetium-177-labeled MDP) radiopharmaceutical could be developed as an agent for palliative radiotherapy of bone pain due to skeletal metastases. Biodistribution studies after intravenous injection of {sup 177}Lu-MDP complex in rats may yield important information to assess its potential for clinical use as a bone pain palliation agent for the treatment of bone metastases. Methods: {sup 177}Lu was produced by irradiating natural Lu{sub 2}O{sub 3} (10 mg) target at a thermal flux {approx}8.0x10{sup 13} n/cm{sup 2} per second for 12 h in the swimming pool-type reactor.{sup 177}Lu was labeled with MDP by adding nearly 37 MBq (1.0 mCi) of {sup 177}LuCl{sub 3} to a vial containing 10 mg MDP. The radiochemical purity and labeling efficiencies were determined by thin layer chromatography. Labeling of {sup 177}Lu with MDP was optimized, and one sample was subjected to high-performance liquid chromatography (HPLC) analysis. Twelve Sprague-Dawley rats were injected with 18.5 MBq (0.5 mCi). {sup 177}Lu-MDP in a volume of 0.1 ml was injected intravenously and then sacrificed at 2 min, 1 h, 2 h and 22 h (three rats at each time point) after injection. Samples of various organs were separated, weighed and measured for radioactivity and expressed as percent uptake of injected dose per gram. Bioevaluation studies with rats under gamma-camera were also performed to verify the results. Results: The quality control using thin layer chromatography has shown >99% radiochemical purity of {sup 177}Lu-MDP complex. Chromatography with Whatman 3

  10. Experimental studies on apoptosis imaging of 153Sm-Annexin V%153Sm-Annexin V凋亡显像的实验研究

    Institute of Scientific and Technical Information of China (English)

    刘江; 赵颖如; 王健; 孙雷娜; 牛瑞芳; 徐文贵

    2013-01-01

      Objective: This work aimed to investigate the feasibility of apoptosis imaging of Annexin V labeled with the radionu-clide 153Sm. Methods: 153Sm-Annexin V was prepared by using the cyclic diethylene triamine pentaacetic acid (DTPA) method, after which physical, chemical, and biological assays of the protein were conducted. Apoptosis imaging experiment both for in vitro cell cul-ture and for tumor-bearing mice was performed using 153Sm-Annexin V. Results: The features of 153Sm-Annexin V prepared via the cy-clic DTPA method are as follows: colorless and transparent, pH 7.4, radioactivity of 100 μg/10 mCi/2 mL, radiochemical purity of over 90%, and 88.6% radiolabeling rate. Annexin V is sterile, pyrogen-free, and presents an LD50 of 333 μg/kg body weight and plasma half-life of 13 min. Positive apoptosis images were obtained from both cultured cells and tumor-bearing mice. Conclusion: 153Sm-An-nexin V, as a radionuclide-labeled apoptosis imaging agent, exhibits a high labeling rate and relatively long half-life. The agent can effi-ciently facilitate continuous tracking and capturing of apoptotic peak activity, thus establishing an optimal apoptosis imaging window period. These advantages indicate that the proposed imaging method has great potential in many clinical applications.%  目的:探讨放射性核素153Sm 标记 Annexin V 凋亡显像的可行性。方法:采用环二乙三胺五醋酸(DTPA)法进行153Sm-Annexin V制备,并进行物理、化学及生物学检测。应用153Sm-Annexin V进行体外细胞培养及荷瘤小鼠动物凋亡显像实验。结果:经环DTPA法制备的153Sm-Annexin V无色透明,pH为7.4,比活度100μg/10 mCi/2 mL;放化纯RCP>90%,标记率为88.6%;无菌,无热原,LD50>333μg/kg体质量,血浆半衰期13 min;体外细胞培养及荷瘤小鼠动物凋亡显像实验均阳性。结论:153Sm-Annex⁃in V作为放射性核素凋亡显像剂,标记率高,半衰期相对较长,利于

  11. (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. PMID:27264196

  12. 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.)

  13. Development of 177Lu-DOTA-anti-CD20 for radioimmunotherapy

    International Nuclear Information System (INIS)

    Rituximab was successively labeled with 177Lu-lutetium chloride. 177Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm-2 s-1) of natural Lu2O3 sample with a specific activity of 2.6-3 GBq/mg. The macrocyclic bifunctional chelating agent, N-succinimidyl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-NHS) was prepared at 25 deg C using DOTA, N-hydroxy succinimide (NHS) in CH2Cl2. DOTA-rituximab was obtained by the addition of 1 mL of a rituximab pharmaceutical solution (5 mg/mL, in phosphate buffer, pH 7.8) to a glass tube pre-coated with DOTA-NHS (0.01-0.1 mg) at 25 deg C with continuous mild stirring for 15 h. Radiolabeling was performed at 37 deg C in 24 h. Radio-thin layer chromatography showed an overall radiochemical purity of >98% at optimized conditions (specific activity = 444 MBq/mg, labeling efficacy; 82%). The final isotonic 177Lu-DOTA-rituximab complex was checked by gel electrophoresis for structure integrity control. Radio-TLC was performed to ensure that only one species was present after filtration through a 0.22 μm filter. Preliminary biodistribution studies in normal rats were carried out to determine complex distribution of the radioimmunoconjugate up to 168 h. The biodistribution data were in accordance with other antiCD20 radioimmunoconjugates already reported. (author)

  14. 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.

  15. Comparative efficacy of 177Lu and 90Y for anti-CD20 pretargeted radioimmunotherapy in murine lymphoma xenograft models.

    Directory of Open Access Journals (Sweden)

    Sofia H L Frost

    Full Text Available 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.Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma or Granta (mantle cell lymphoma xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA-biotin second step reagent.The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq as for 177Lu (0.6 Gy/MBq. More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes.90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma

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

    International Nuclear Information System (INIS)

    Purpose 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. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

  17. Biological effective doses in 300 patients undergoing therapy with 177Lu-octreotate

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: fractionated therapy with 177Lu-octreotate has been reported to be an effective treatment option for patients with generalized neuroendocrine tumors. The main aim of this study was to calculate the biological effective dose (BED) to the kidneys using an individualized dosimetry protocol, and to assess differences in the number of possible treatment cycles based on BED compared to those based on absorbed dose. Methods: a total of 148 female and 152 male patients with neuroendocrine tumors with high somatostatin receptor expression (grade 3 or 4) were included. After infusion of 7.4 GBq of 177Lu-octreotate SPECT/CT images over the abdomen were acquired at 24, 96 and 168 h after infusion. Absorbed dose to kidneys was calculated based on pharmacokinetic data obtained from SPECT/CT. From this the effective half-life of 177Lu-octreotate in the kidneys was estimated, and BED was calculated using the equation described by Barone et al. (1). Results and discussion: for a single treatment cycle of 7.4 GBq, median (1:st-3:rd quartiles) BED was 5.0 Gy (3.9-6.1) in the right kidney and 4.7 Gy (3.7-5.8) in the left kidney. For the same treatment cycle, BED was 9.0% (7.1-11.3) and 8.7% (7.0-10.9) higher than absorbed dose in right and left kidneys, respectively. In patients with high absorbed doses, BED could be more than 20% higher than absorbed dose. Assuming an absorbed dose limit of 23 Gy and a BED limit of 45 Gy to the kidneys, the possible number of treatment cycles was 5.4 (4.5-6.8) based on absorbed dose while using BED increased the number of possible cycles to 9.8 (8.1-12.5). Conclusions: although biological effective dose to the kidneys is higher than absorbed dose, use of BED to estimate the number of possible treatment cycles in 177Lu-octreotate therapy may allow for more treatment cycles than the use of absorbed dose. Refs: 1) Barone, R. et al. Patient-specific dosimetry in predicting renal toxicity with (90)Y

  18. {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.)

  19. Cytogenetic effect of 153 Sm-EDTMP in peripheral lymphocytes of patients with metastatic cancer

    International Nuclear Information System (INIS)

    The 153Sm-EDTMP is a radiopharmaceutical used in nuclear medicine with promising results for the relief of metastatic pain. Therefore, there are few knowledge about the effects of 153Sm-EDTMP at cellular level. The present study was conduced with the aim of evaluating the cytogenetic effects of 153Sm-EDTMP in peripheral lymphocytes from patients with bone metastasis (with and without previous radio and/or chemotherapy) by the chromosome aberration technique, either in vivo or in vitro. For that, the blood samples were collected before and one hour after the endovenous administration of 153Sm-EDTMP (mean activity of 42.53+/-5.31 MBq/kg body weight), taking into account the rapid blood clearance. The principal types of structural chromosome aberrations found gaps and breaks, acentric fragments centric rings, double minutes and dicentrics. The statistical analysis showed that the group submitted to previous radio and chemotherapy before 153Sm-EDTMP administration showed significant difference in chromosome aberrations frequency one hour after the treatment. The analysis of the chromosome modal number and the kinetics of cellular cycle showed no statistical difference among the groups, suggesting that the treatment with 153Sm-EDTMP, did not influence these parameters. The carrier molecule, EDTMP, did not influence the induction of chromosome aberration. In relation to the in vitro assays, the obtained data of peripheral lymphocytes of healthy donors and patients with no previous treatment exposed to different radioactive concentration of 153Sm-EDTMP (0.046 - 1.110 MBq/mL) were better adjusted by linear regression model (Y=A+BX). The chromosome damage induced by 153Sm-EDTMP observed in vitro was about 2 fold higher than that found in vivo for the group of patients with no previous treatment. The obtained data showed that the therapy with 153Sm-EDTMP induced a few quantity of cytogenetic damages in peripheral lymphocytes on hour after its administration in patients

  20. The content of 153Sm-oxabifor in cancer patients blood in the treatment of bone metastasis

    International Nuclear Information System (INIS)

    Concentration 153Sm in the blood of patients with bone metastasis after radionuclide therapy was determined. Considerable variation of the content of 153Sm in blood of patients with various primary cancers from 10 to 65 Bq/ml is found. The effective half-life of 153Sm in the blood of patients was estimated at more than 10 days during the course of the therapy in time interval more than 7 days

  1. Kinetics of 153Sm oxabiphor in the blood of cancer patients undergoing complex therapy for bone metastasis

    International Nuclear Information System (INIS)

    Concentration 153Sm in the blood of patients with bone metastasis after radionuclide therapy was determined. Considerable variation of the content of 153Sm in blood of patients with various primary cancers from 10 to 65 Bq/ml is found. The effective half-life of 153Sm in the blood of patients was estimated at more than 10 days during the course of the therapy.

  2. Is 161Tb and alternative to 177Lu? In vitro and in vivo comparison using DOTA-Folate conjugates

    International Nuclear Information System (INIS)

    Full text of publication follows. Background: The radio-lanthanide 161Tb decays with a half-life of 165.4 h by emission of low energy β- particles and Auger-e- for therapeutic purposes and γ-radiation suitable for SPECT. 161Tb was recently proposed as a potential alternative to 177Lu for targeted radionuclide tumor therapy [Refs.1,2]. The goal of this study was to compare 161Tb and 177Lu using a tumor targeted DOTA-folate conjugate (cm09 [Ref.3]). Methods. 161Tb was produced by a previously published procedure at PSI [Refs.2,3]. 177Lu was obtained from ITG GmbH, Munich, Germany). Radiolabeling of cm09 was carried out by incubation of the reaction mixture at 95 C. degrees for 10 min. In vitro the effects of 161Tb-cm09 and 177Lu-cm09 were tested on folate receptor (FR)-positive KB cells using an MTT viability assay. In vivo the therapeutic effects of 161Tb-cm09 and 177Lu-cm09 (10 MBq, 0.5 nmol) were compared over 7 weeks in KB tumor bearing mice. Results: 161TbCl3 was prepared in an excellent quality and at high radioactivity concentration. Both, 161Tb-cm09 and 177Lu-cm09 were obtained at high purity (> 98%) at a specific activity of > 40 MBq/nmol. In KB tumor cells, 161Tb-cm09 reduced cell viability more effectively than 177Lu-cm09 (161Tb-cm09: IC50 ∼ 0.014 MBq/ml versus 177Lu-cm09: IC50: ∼ 0.063 MBq/ml). In vivo 161Tb-cm09 showed an increased therapeutic efficacy to reduce tumor growth compared to 177Lu-cm09 which was in agreement with an increased absorbed tumor dose (3.3 Gy/MBq for 161Tb-cm09 versus 2.4 Gy/MBq for 177Lu-cm09). Hence an increased average survival time was observed for mice treated with 161Tb-cm09 (54 d) compared to 177Lu-cm09 (35 d). Conclusions. In this study we demonstrated increased therapeutic efficacy of 161Tb-cm09 compared to 177Lu-cm09 to reduce tumor cell growth in vitro and in vivo. Further investigations with other tumor targeting agents will be necessary to draw final conclusions about the future clinical perspectives of 161Tb

  3. 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.

  4. Uncertainty propagation for SPECT/CT-based renal dosimetry in 177Lu peptide receptor radionuclide therapy

    Science.gov (United States)

    Gustafsson, Johan; Brolin, Gustav; Cox, Maurice; Ljungberg, Michael; Johansson, Lena; Sjögreen Gleisner, Katarina

    2015-11-01

    A computer model of a patient-specific clinical 177Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of 177Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity.

  5. Uncertainty propagation for SPECT/CT-based renal dosimetry in (177)Lu peptide receptor radionuclide therapy.

    Science.gov (United States)

    Gustafsson, Johan; Brolin, Gustav; Cox, Maurice; Ljungberg, Michael; Johansson, Lena; Gleisner, Katarina Sjögreen

    2015-11-01

    A computer model of a patient-specific clinical (177)Lu-DOTATATE therapy dosimetry system is constructed and used for investigating the variability of renal absorbed dose and biologically effective dose (BED) estimates. As patient models, three anthropomorphic computer phantoms coupled to a pharmacokinetic model of (177)Lu-DOTATATE are used. Aspects included in the dosimetry-process model are the gamma-camera calibration via measurement of the system sensitivity, selection of imaging time points, generation of mass-density maps from CT, SPECT imaging, volume-of-interest delineation, calculation of absorbed-dose rate via a combination of local energy deposition for electrons and Monte Carlo simulations of photons, curve fitting and integration to absorbed dose and BED. By introducing variabilities in these steps the combined uncertainty in the output quantity is determined. The importance of different sources of uncertainty is assessed by observing the decrease in standard deviation when removing a particular source. The obtained absorbed dose and BED standard deviations are approximately 6% and slightly higher if considering the root mean square error. The most important sources of variability are the compensation for partial volume effects via a recovery coefficient and the gamma-camera calibration via the system sensitivity. PMID:26458139

  6. 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.

  7. Reducing Renal Uptake of 177Lu Labeled CCK Derivative using Basic Amino Acids

    International Nuclear Information System (INIS)

    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 177Lu-DOTA-CCK derivative. Renal uptake of 177Lu-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

  8. 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.

  9. 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.

  10. Amifostine protects rat kidneys during peptide receptor radionuclide therapy with [177Lu-DOTA0,Tyr3]octreotate

    International Nuclear Information System (INIS)

    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 [177Lu-DOTA0,Tyr3]octreotate. Male Lewis rats were injected with 278 or 555 MBq [177Lu-DOTA0,Tyr3]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 99mTc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [177Lu-DOTA0,Tyr3]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 [177Lu-DOTA0,Tyr3]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 99mTc-DMSA SPECT scintigrams at 130 days after [177Lu-DOTA0,Tyr3]octreotate therapy correlated well with 1/creatinine (r 2 = 0.772, p 177Lu-DOTA0,Tyr3]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. (orig.)

  11. Standardization of {sup 153}Sm using anti-coincidence method; Padronizacao do {sup 153}Sm pelo metodo de anti-coincidencia

    Energy Technology Data Exchange (ETDEWEB)

    Laranjeira, Adilson da Silva; Silva, Carlos J. da; Delgado, Jose Ubiratan; Cruz, Paulo A.L. da; Poledna, Roberto; Silva, Ronaldo L. da; Oliveira, Antonio E. de; Gomes, Regio S.; Veras, Eduardo V. de; Araujo, Miriam Taina Ferreira de, E-mail: adilson@ird.gov.br [Instituto de Radioprotecao e Dosimetria, (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)

    2014-07-01

    {sup 153}Sm was standardized at the Brazilian National Laboratory of Metrology of Ionizing Radiation to provide traceability for measurements in nuclear medicine services and manufacturers of radiopharmaceuticals in Brazil. {sup 153}Sm decays by emission β-γ to {sup 153}Eu, the gamma rays of higher-intensity are 69.7 keV (4.7%) and 103.2 keV (29.2%). The standardization was made by anticoincidence and CIEMAT/NIST methods with uncertainties combined (0.4% and 0.3%) and (0.5% and 0.4%), respectively. The difference between the standardized activities was 0.15%. The uncertainties are consistent with other publications. (author)

  12. Direct in vitro and in vivo comparison of 161Tb and 177Lu using a tumour-targeting folate conjugate

    International Nuclear Information System (INIS)

    The radiolanthanide 161Tb (T1/2 = 6.90 days, Eβ-av = 154 keV) was recently proposed as a potential alternative to 177Lu (T1/2 = 6.71 days, Eβ-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 161Tb and 177Lu in vitro and in vivo using a tumour-targeted DOTA-folate conjugate (cm09). 161Tb-cm09 and 177Lu-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 161Tb-cm09 and 177Lu-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 99mTc-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 161Tb-cm09 (IC50 ∝0.014 MBq/ml and ∝2.53 MBq/ml) compared to 177Lu-cm09 (IC50 ∝0.063 MBq/ml and ∝4.52 MBq/ml). SPECT imaging visualized tumours of mice with both radioconjugates. However, in therapy studies 161Tb-cm09 reduced tumour growth more efficiently than 177Lu-cm09. These findings were in line with the higher absorbed tumour dose for 161Tb-cm09 (3.3 Gy/MBq) compared to 177Lu-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 177Lu-cm09 we demonstrated equal imaging features for 161Tb-cm09 but an increased therapeutic efficacy for 161Tb-cm09 in both tumour cell lines in vitro and in vivo. Further preclinical

  13. Evaluation of radiation safety in (177)Lu-PSMA therapy and development of outpatient treatment protocol.

    Science.gov (United States)

    Demir, Mustafa; Abuqbeitah, Mohammad; Uslu-Beşli, Lebriz; Yıldırım, Özlem; Yeyin, Nami; Çavdar, İffet; Vatankulu, Betül; Gündüz, Hüseyin; Kabasakal, Levent

    2016-06-01

    The aim of this study is to investigate the outpatient treatment protocol and radiation safety of a new-emerging lutetium-177 ((177)Lu) prostate specific membrane antigen (PSMA) therapy. This work analyzed the dose rate of 23 patients treated with 7400 MBq (177)Lu-PSMA at different distances (0, 0.25, 0.50, 1.0 and 2.0 m) and variable time marks (0, 1, 2, 4, 18, 24, 48 and 120 h) after the termination of infusion. Blood samples were withdrawn from 17 patients within the same group at 3, 10, 20, 40, 60 and 90 min and 2, 3, 24 h after termination of infusion. Seven different patients were asked to collect urine for 24 h and a gamma well counter was used for counting samples. Family members were invited to wear an optically stimulated luminescence dosimeter whenever they were in the proximity of the patients up to 4-5 d. The total dose of the medical team including the radiopharmacist, physicist, physician, nurse, and nuclear medicine technologist was estimated by an electronic personnel dosimeter. The finger dose was determined using a ring thermoluminescent dosimeter for the radiopharmacist and nurse. The mean dose rate at 1 m after 4 h and 6 h was 23  ±  6 μSv h(-1) and 15  ±  4 μSv h(-1) respectively. The mean total dose to 23 caregivers was 202.3  ±  42.7 μSv (range: 120-265 μSv). The radiation dose of the nurse and radiopharmacist was 6 and 4 μSv per patient, respectively, whereas the dose of the physicist and physician was 2 μSv. The effective half life of blood distribution and early elimination was 0.4  ±  0.1 h and 5  ±  1 h, respectively. Seven patients excreted a mean of 45% (range: 32%-65%) from the initial activity in 6 h. Our findings demonstrate that (177)Lu-PSMA is a safe treatment modality to be applied as an outpatient protocol, since the dose rate decreases below the determined threshold of  <30 μSv h(-1) after approximately 5 h and degrades to 20 μSv h(-1) after 6

  14. 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

  15. 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

  16. IMPROVED PLANAR KIDNEY ACTIVITY CONCENTRATION ESTIMATE BY THE POSTERIOR VIEW METHOD IN 177LU-DOTATATE TREATMENTS.

    Science.gov (United States)

    Magnander, Tobias; Svensson, Johanna; Båth, Magnus; Gjertsson, Peter; Bernhardt, Peter

    2016-06-01

    The aims of this study were to determine how different background regions of interest (ROIs) around the kidney represent true background activity in over- and underlying tissues in (177)Lu-DOTA-octreatate ((177)Lu-DOTATATE) treatments and to determine the influence of the background positions on the kidney activity concentration estimates by the conjugate view (ConjV) and posterior view (PostV) methods. The analysis was performed in single-photon emission computed tomography (SPECT) images of 20 patients, acquired 24 h post injection of a (177)Lu-DOTATATE treatment, by a computer algorithm that created planar images from the SPECT data. The ratio between the activity concentration in the background and the true background varied from 0.36 to 2.08 [coefficient of variation (CV) = 25-181 %] and from 0.44 to 1.52 (CV = 16-70 %) for the right and left kidneys, respectively. The activity concentration estimate in the kidneys was most accurate with the PostV method using a background ROI surrounding the whole kidney, and this combination might be an alternative planar method for improved kidney dosimetry in the (177)Lu-DOTATATE treatments. PMID:27012883

  17. Preparation, Characterization and Stability Test of 177Lu-CTMP as Palliative Agent For Bone Pain Metastases

    International Nuclear Information System (INIS)

    177Lu-CTMP is an ideal radiopharmaceutical for palliative agent on bone pain metastases. This radiopharmaceutical was synthesized from cyclic polyaminophosphonic ligand, known as 1,4,8,11-tetraazacycIotetradecane-l, 4,8,11 tetramethylene phosphonic acid (CTMP) and labeled with 177Lu radio nuclide, a beta emitter which has long enough half life (t1/2=6.71 days, E β-max= 497 KeV). The labeling method was modified from Tapas Das Method by changing buffer type. Ammonium carbonate buffer was changed by phosphate buffer. In this research some variables were used. such as mol comparison (Lu:CTMP), pH variation, and reaction temperature. The result, indicated that an optimum condition of 177Lu-ClMP preparation was at mol comparison Lu:CTMP= 1:20, pH=7, and at room temperature. Optimum labeling of 177Lu-CTMP has been tested using paper chromatography, giving 99.4 % of radiochemical purity. From the stability test, it was found that the radiopharmaceutical was stable until 10 days (when it stored in room temperature and 4°C). After 10 days, decreasing of radiochemical purity, was found if stored in room temperature ( below of the required radiochemical purity «95%)). However, when it was stored at 4°C, it was stable until 21 days with a good condition (radiochemical purity >95%). (author)

  18. 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.

  19. Uptake of 153Sm-EDTMP in normal, benign and malignant tumor tissue

    CERN Document Server

    Riegel, A

    2001-01-01

    The present study was designed to investigate and compare the uptake of 153Sm-EDTMP (153Samarium-ethylenediaminetetramethylene phosphonate)and 99mTc-DPD (99mTechnetium-dicarboxypropane diphosphonate) into different soft tissue sarcoma cell lines and various tissue specimen in vitro. After 10-120 minutes of incubation at 22 sup o C and 37 sup o C with 153Sm-EDTMP, the uptake kinetics of this tracer in human soft tissue sarcoma cells SW 684 (fibrosarcoma) and SW 1353 (chondrosarcoma) were assessed. The uptake was temperature-dependent and higher into fibrosarcoma than in chondrosarconma. Normal bone tissue samples of rat and human were incubated with 153Sm-EDTMP and 99mTc-DPD. The uptake of 99mTc-DPD was higher than that of 153Sm-EDTMP. Various benign and malignant bone and soft tissue tumors and metastases of different primaries were treated in the same way. The uptake was generally very low, in the metastatic tissue specimen in part possibly due to their osteolytic character.

  20. Anti-EGFRvIII monoclonal antibody armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Hens, Marc; Vaidyanathan, Ganesan; Zhao Xiaoguang [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States); Bigner, Darell D. [Department of Pathology, Duke University Medical Center, Durham, NC 27710 (United States); Zalutsky, Michael R., E-mail: zalut001@mc.duke.ed [Department of Radiology, Duke University Medical Center, Durham, NC 27710 (United States)

    2010-10-15

    Introduction: Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not on normal tissues, and is internalized rapidly after receptor binding. Because of the short range of its {beta}-emissions, labeling this mAb with {sup 177}Lu would be an attractive approach for the treatment of residual tumor margins remaining after surgical debulking of brain tumors. Materials and Methods: L8A4 mAb was labeled with {sup 177}Lu using the acyclic ligands [(R)-2-amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1, 2-diamine-pentaacetic acid (CHX-A''-DTPA) and 2-(4-isothiocyanatobenzyl)-6-methyldiethylene-triaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and {alpha}-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7, 10-tetraacetic acid (MeO-DOTA). Paired-label tissue distribution experiments were performed in athymic mice bearing subcutaneous EGFRvIII-expressing U87.{Delta}EGFR glioma xenografts over a period of 1 to 8 days to directly compare {sup 177}Lu-labeled L8A4 to L8A4 labeled with {sup 125}I using N-succinimidyl 4-guanidinomethyl-3-[{sup 125}I]iodobenzoate ([{sup 125}I]SGMIB). Results: Except with C-DOTA, tumor uptake for the {sup 177}Lu-labeled mAb was significantly higher than the co-administered radioiodinated preparation; however, this was also the case for spleen, liver, bone and kidneys. Tumor/normal tissue ratios for {sup 177}Lu-1B4M-DTPA-L8A4 and, to an even greater extent, {sup 177}Lu-MeO-DOTA-L8A4 were higher than those for [{sup 125}I]SGMIB-L8A4 in most other tissues. Conclusions: Tumor and normal tissue distribution patterns for this anti-EGFRvIII mAb were dependent on the nature of the bifunctional chelate used for {sup 177}Lu labeling. Optimal results were obtained with 1B4M-DTPA and MeO-DOTA, suggesting no clear advantage

  1. Tumor response assessment to treatment with [177Lu-DOTA0,Tyr3]octreotate in patients with gastroenteropancreatic and bronchial neuroendocrine tumors: differential response of bone versus soft-tissue lesions.

    NARCIS (Netherlands)

    Vliet, E.I. van; Hermans, J.J.; Ridder, M.A. de; Teunissen, J.J.; Kam, B.L.; Krijger, R.R. de; Krenning, E.P.; Kwekkeboom, D.J.

    2012-01-01

    We have noted that bone lesions on CT respond differently from soft-tissue lesions to treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate). We therefore compared the response of bone lesions with that of soft-tissue lesions to treatment with (177)Lu-octreotate in patients with gast

  2. 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.

  3. Hormonal crises following receptor radionuclide therapy with the radiolabeled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate

    Energy Technology Data Exchange (ETDEWEB)

    Keizer, Bart de; Kam, Boen L.R.; Essen, Martijn van; Krenning, Eric P.; Kwekkeboom, Dik J. [Erasmus Medical Center, Department of Nuclear Medicine, Rotterdam, P.O. Box 2040 (Netherlands); Aken, Maarten O. van; Feelders, Richard A.; Herder, Wouter W. de [Erasmus Medical Center, Section of Endocrinology, Department of Internal Medicine, Rotterdam (Netherlands)

    2008-04-15

    Receptor radionuclide therapy is a promising treatment modality for patients with neuroendocrine tumors for whom alternative treatments are limited. The aim of this study was to investigate the incidence of hormonal crises after therapy with the radiolabeled somatostatin analogue [{sup 177}Lu-DOTA{sup 0},Tyr{sup 3}]octreotate ({sup 177}Lu-octreotate). All {sup 177}Lu-octreotate treatments between January 2000 and January 2007 were investigated. Four hundred seventy-six patients with gastroenteropancreatic neuroendocrine tumors and three patients with metastatic pheochromocytoma were included for analysis. Four hundred seventy-nine patients received a total of 1,693 administrations of {sup 177}Lu-octreotate. Six of 479 patients (1%) developed severe symptoms because of massive release of bioactive substances after the first cycle of {sup 177}Lu-octreotate. One patient had a metastatic hormone-producing small intestinal carcinoid; two patients had metastatic, hormone-producing bronchial carcinoids; two patients had vasoactive intestinal polypeptide-producing pancreatic endocrine tumors (VIPomas); and one patient had a metastatic pheochromocytoma. With adequate treatment, all patients eventually recovered. Hormonal crises after {sup 177}Lu-octreotate therapy occur in 1% of patients. Generally, {sup 177}Lu-octreotate therapy is well tolerated. (orig.)

  4. Labelling of Dotatate with 177Lu and 131I for diagnosis and targeted therapy: In vitro and In vivo comparative evaluation

    International Nuclear Information System (INIS)

    The studies focused on the radiolabelling of DOTA-Tyr3-TATE (DOTATATE) with 177Lu and 131I, on the biological behaviour of 177Lu-DOTATATE and 131IDOTATATE and on comparative evaluation of the results obtained to select an appropriate radiopeptide for potential application in somatostatin receptor radionuclide therapy. The radiopeptides were obtained with high purities and specific activities, but with different stabilities, with the 177Lu-DOTATATE being more stable than the 131IDOTATATE. The results of competition and saturation binding experiments using rat brain cortex membrane homogenates show a high in vitro affinity (IC50: 4.74nM, Kd: 142.8 for 177Lu-DOTATATE; IC50: 1.28nM, Kd: 157.6 for 131I-DOTATATE). The biodistribution of each radiopeptide as well as the competitive biodistribution of 177Lu- DOTATATE and 131I-DOTATATE in rats bearing HRS1 (Hepatom RS1, a hepatocolangiom carcinoma) tumours illustrate that 177Lu-DOTATATE is more stable and shows better tumour uptake than 131I-DOTATATE, and that the competitive localization index of 177Lu-DOTATATE is three times higher than that of 131I-DOTATATE. The flow cytometry measurements of the HRS1 tumour samples from rats treated with multiple doses of 177Lu-DOTATATE in combination with absorbed dose data show decreases of both the tumour cell proliferation index and DNA ploidy. These data indicate that 177Lu- DOTATATE is a good option for application in somatostatin receptor radionuclide therapy. (author)

  5. Fast voxel-level dosimetry for 177Lu labelled peptide treatments

    Science.gov (United States)

    Hippeläinen, E.; Tenhunen, M.; Sohlberg, A.

    2015-09-01

    In peptide receptor radionuclide therapy (PRRT), voxel-level radiation absorbed dose calculations can be performed using several different methods. Each method has it strengths and weaknesses; however, Monte Carlo (MC) simulation is presently considered the most accurate method at providing absorbed dose distributions. Unfortunately MC simulation is time-consuming and often impractical to carry out in a clinical practice. In this work, a fast semi-Monte Carlo (sMC) absorbed dose calculation method for 177Lu PRRT dosimetry is presented. The sMC method is based on a local electron absorption assumption and fast photon MC simulations. The sMC method is compared against full MC simulation code built on PENELOPE (vxlPen) using digital phantoms to assess the accuracy of these assumptions. Due to the local electron absorption assumption of sMC, the potential errors in cross-fire dose from electrons and photons emitted by 177Lu were first evaluated using an ellipsoidal kidney model by comparing vxlPen and sMC. The photon cross-fire dose from background to kidney and kidney to background with varying kidney-to-background activity concentration ratios were calculated. In addition, kidney to kidney photon and electron cross-dose with different kidney to kidney distances were studied. Second, extended cardiac-torso (XCAT) phantoms were created with liver lesions and with realistic activity distributions and tissue densities. The XCAT phantoms were used to simulate SPECT projections and 3D activity distribution images were reconstructed using an OSEM algorithm. Image-based dose rate distributions were calculated using vxlPen and sMC. Total doses and dose rate volume histograms (DrVH) produced by the two methods were compared. The photon cross-fire dose from the kidney increased the background’s absorbed dose by 5% or more up to 5.8 cm distance with 20 : 1 kidney to background activity concentration ratio. On the other hand, the photon cross-fire dose from the background to

  6. 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

  7. Labelling of MoAb with 153SmH1ETA: Preliminary results

    International Nuclear Information System (INIS)

    A method to label MoAb with Sm-153 using 1,5,9,13-tetraazacyclohexadecane N,N',N'',N''' tetraacetic acid (H4ETA) as a bifunctional chelator was developed. H4ETA and SmH1ETA were synthesized in our laboratory and characterized by IR spectroscopy, TGA (thermogravimetric analysis), SEM (Scattering Electronic Microscopy), EDAX (Elemental Dispersion Analysis by X-rays) and EPR (Electron Paramagnetic Resonance) at 6 K. The 153SmH1ETAMoAb was prepared by a simple incubation of the MoAb ior cea1, and the 153SmH1ETA complex at neutral pH and at room temperature for 24 h. The specific activity of the labelled antibody was 111 MBq/mg (3 mCi/mg). Sm-153(III) is commercially available with specific activities up to 318.2 GBq/mg. Therefore, under the conditions described above 153SmH1ETA labelled MoAb could be obtained with specific activity up to 1.14 GBq/mg (30.7 mCi/mg). (author)

  8. Evaluation of the therapeutic efficacy and radiotoxicity of the conjugates 177Lu-DOTA-E-c(RGDfK)2 and 177Lu-DOTA-GGC-AuNP-c[RGDfk(C)] in a murine model and their relationship with the inhibition of the angiogenic factors VEGF and HIF-1α

    International Nuclear Information System (INIS)

    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 177Lu-AuNP-RGD in athymic mice bearing α(v)β(3)-integrin-positive C6 gliomas and compare with that of 177Lu-AuNP or 177Lu-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 177Lu-AuNP-RGD, 177Lu-AuNP or 177Lu-RGD were assessed. Of the radiopharmaceuticals evaluated, 177Lu-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 177Lu-AuNP-RGD significantly (p177Lu). There was a low uptake in non-target organs and no induction of renal toxicity. 177Lu-AuNP-RGD demonstrates properties suitable for use as an agent for molecular targeting radiotherapy. (Author)

  9. 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.

  10. 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.

  11. 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.)

  12. {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.)

  13. Production and first use of 153SmCl3-ion exchange resin capsule formulation for assessing gastrointestinal motility

    International Nuclear Information System (INIS)

    We produced an enteric-coated gelatine capsule containing neutron-activated 153Sm-labelled resin beads for use in gastrointestinal motility studies. In vitro test in simulated gastrointestinal environment and in vivo study on volunteers were performed. Scintigraphic images were acquired from ten volunteers over 24 h while blood and urine samples were collected to monitor the presence of 153Sm. All the capsules remained intact in stomach. This proved to be a safe and practical oral capsule formulation for whole gut transit scintigraphy. - Highlights: ► Enteric-coated gelatin capsule containing 153Sm-labelled resin was manufactured. ► In vitro disintegration test ensured targeted release properties of the formulation. ► In vivo volunteers study confirmed safeness and practical use of the formulation. ► 153Sm can be used as an alternative nuclide to 111In in GI transit scintigraphy.

  14. Scintigraphic dynamics valuation of bone metastasis in the course of the treatment of 153Sm-oksabifor

    International Nuclear Information System (INIS)

    In the present study we examined the role of bone scan with 99mTc-pyrophosphate treatment planning 153Sm-oksabifor followed by analysis of post-treatment monitoring of cancer patients with bone metastases

  15. Production of glass microspheres comprising 90Y and 177Lu for treating of hepatic tumors with SPECT imaging capabilities

    International Nuclear Information System (INIS)

    Our objective was to determine if glass microspheres impregnated with two radionuclides,90Y as source of therapeutic beta emissions and 177Lu as source of diagnostic gamma emissions can be useful for SPECT imaging during or after application of the 90Y microspheres for treating of hepatic tumors. The glass-based microspheres labeled with 89Y and lutetium (YAS (Lu)) or 89Y and ytterbium (YAS (Yb)) were prepared by the sol-gel process where sol droplets directly were formed to gel microspheres. Results of the neutron activation indicate that such a combination of glass, microspheres allow bio-distribution studies by SPECT imaging with high resolution. - Highlights: → A radioactive microsphere composed of glass was impregnated with two radionuclide 90Y and 177Lu. 177Lu is as a dopant for diagnostic gamma emissions. → The glass-based microspheres labeled with 89Y and lutetium (YAS (Lu)) or 89Y and ytterbium (YAS (Yb)) were prepared by the sol-gel process where gel microspheres directly were formed from sol droplets. → After neutron activation, such a combination of glass, allows SPECT imaging so bio-distribution is possible with better resolution.

  16. Pharmacokinetic digital phantoms for accuracy assessment of image-based dosimetry in 177Lu-DOTATATE peptide receptor radionuclide therapy

    Science.gov (United States)

    Brolin, Gustav; Gustafsson, Johan; Ljungberg, Michael; Sjögreen Gleisner, Katarina

    2015-08-01

    Patient-specific image-based dosimetry is considered to be a useful tool to limit toxicity associated with peptide receptor radionuclide therapy (PRRT). To facilitate the establishment and reliability of absorbed-dose response relationships, it is essential to assess the accuracy of dosimetry in clinically realistic scenarios. To this end, we developed pharmacokinetic digital phantoms corresponding to patients treated with 177Lu-DOTATATE. Three individual voxel phantoms from the XCAT population were generated and assigned a dynamic activity distribution based on a compartment model for 177Lu-DOTATATE, designed specifically for this purpose. The compartment model was fitted to time-activity data from 10 patients, primarily acquired using quantitative scintillation camera imaging. S values for all phantom source-target combinations were calculated based on Monte-Carlo simulations. Combining the S values and time-activity curves, reference values of the absorbed dose to the phantom kidneys, liver, spleen, tumours and whole-body were calculated. The phantoms were used in a virtual dosimetry study, using Monte-Carlo simulated gamma-camera images and conventional methods for absorbed-dose calculations. The characteristics of the SPECT and WB planar images were found to well represent those of real patient images, capturing the difficulties present in image-based dosimetry. The phantoms are expected to be useful for further studies and optimisation of clinical dosimetry in 177Lu PRRT.

  17. 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)

  18. Biokinetics and dosimetry with 177Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    Science.gov (United States)

    Rodríguez-Cortés, J.; de Murphy, C. Arteaga; Ferro-Flores, Ge; Pedraza-López, M.; Murphy-Stack, E.

    Malignant pancreatic tumours induced in athymic mice are a good model for peptide receptor targeted radiotherapy. The objective of this research was to determine biokinetic parameters in mice, in order to estimate the induced pancreatic tumour absorbed doses and to evaluate an `in house' 177Lu-DOTA-TATE radiopharmaceutical as part of preclinical studies for targeted therapy in humans. AR42J murine pancreas cancer cells expressing somatostatin receptors, were implanted in athymic mice (nD22) to obtain biokinetic and dosimetric data of 177Lu-DOTA-TATE. The mean tumour uptake 2 h post injection was 14.76±1.9% I.A./g; kidney and pancreas uptake, at the same time, were 7.27±1.1% I.A./g (1.71±0.90%/organ) and 4.20±0.98% I.A./g (0.42±0.03%/organ), respectively. The mean absorbed dose to tumour, kidney and pancreas was 0.58±0.02 Gy/MBq; 0.23±0.01 Gy/MBq and 0.14±0.01 Gy/MBq, respectively. These studies justify further dosimetric estimations to ensure that 177Lu-DOTA-TATE will act as expected in humans.

  19. {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.)

  20. 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.)

  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. 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)

  4. Combined use of zoledronic acid and 153Sm-EDTMP in hormone-refractory prostate cancer patients with bone metastases

    Energy Technology Data Exchange (ETDEWEB)

    Lam, Marnix G.E.H.; Rijk, Peter P. van [University Medical Center Utrecht, Department of Nuclear Medicine, P.O. Box 85500, Utrecht (Netherlands); Dahmane, Amel; Stevens, Wil H.M. [CIS bio International, Saclay (France); Klerk, John M.H. de [Meander Medical Center, Department of Nuclear Medicine, Amersfoort (Netherlands); Zonnenberg, Bernard A. [UMC Utrecht, Department of Internal Medicine, Utrecht (Netherlands)

    2008-04-15

    {sup 153}Sm-ethylenediaminetetramethylenephosphonic acid (EDTMP; Quadramet {sup registered}) is indicated for the treatment of painful bone metastases, whereas zoledronic acid (Zometa {sup registered}) is indicated for the prevention of skeletal complications. Because of the different therapeutic effects, combining the treatments may be beneficial. Both, however, accumulate in areas with increased osteoblastic activity. Possible drug interactions were investigated. Patients with hormone-refractory prostate cancer were treated with 18.5 MBq/kg {sup 153}Sm-EDTMP in weeks 1 and 3 and with 37 MBq/kg in week 15. Treatment with 4 mg zoledronic acid began in week 3 and continued every 4 weeks through week 23. In weeks 3 and 15, zoledronic acid was administered 2 days before {sup 153}Sm-EDTMP treatment. Urine was collected 48 h after injection of {sup 153}Sm-EDTMP, and whole-body images were obtained 6, 24 and 48 h post-injection. The effect of zoledronic acid on total bone uptake of {sup 153}Sm-EDTMP was measured indirectly by the cumulative activity excreted in the urine in weeks 1, 3 and 15. Biodistribution, safety, tolerability and effect on prostate-specific antigen level were also studied. The urinary excretion in week 3 divided by the urinary excretion in week 1 (baseline) times 100% was mean 98.4 {+-} 11.6% (median 96.2%). From week 1 to 15, after four zoledronic acid treatments, the mean ratio was 101.9 {+-} 10.7% (median 101.8%). Bioequivalence could be concluded by using a two-sample t test for both per-protocol (n = 13) and full-analysis sets (n = 18). Toxicity was comparable to of monotherapy with {sup 153}Sm-EDTMP. Zoledronic acid treatment does not influence {sup 153}Sm-EDTMP skeletal uptake. Combined treatment is feasible and safe. (orig.)

  5. Study on the synthesis of AMP derivatives for labeling with 153Sm and 166Ho

    International Nuclear Information System (INIS)

    This study describes the synthesis method and characterization of AMP-( Aminomethylene phosphonic acid): (PDTMP; BDTMP; DMPDTMP). AMP is synthesized by the condensation of correlative diamine, phosphorous acid and formaldehyde using a modified Mannich reaction in the presence of hydrochloric acid. Recrystallization of the crude product from water yields white crystals of pure legend, and subsequently characterized using 1H-NMR, IR spectroscopy, melting point, crystal picture, element analysis, metal trace analysis. Synthesized AMP, when tagged with therapeutic radio nuclides such as 153Sm and 166Ho are quite good. Complexes with RC purity and labeling efficiency 20 - 98% and above could be prepared by ordinary reaction condition. (author)

  6. Radionuclide therapy of HER2-positive microxenografts using a 177Lu-labeled HER2-specific Affibody molecule.

    Science.gov (United States)

    Tolmachev, Vladimir; Orlova, Anna; Pehrson, Rikard; Galli, Joakim; Baastrup, Barbro; Andersson, Karl; Sandström, Mattias; Rosik, Daniel; Carlsson, Jörgen; Lundqvist, Hans; Wennborg, Anders; Nilsson, Fredrik Y

    2007-03-15

    A radiolabeled anti-HER2 Affibody molecule (Z(HER2:342)) targets HER2-expressing xenografts with high selectivity and gives good imaging contrast. However, the small size (approximately 7 kDa) results in rapid glomerular filtration and high renal accumulation of radiometals, thus excluding targeted therapy. Here, we report that reversible binding to albumin efficiently reduces the renal excretion and uptake, enabling radiometal-based nuclide therapy. The dimeric Affibody molecule (Z(HER2:342))(2) was fused with an albumin-binding domain (ABD) conjugated with the isothiocyanate derivative of CHX-A''-DTPA and labeled with the low-energy beta-emitter (177)Lu. The obtained conjugate [CHX-A''-DTPA-ABD-(Z(HER2:342))(2)] had a dissociation constant of 18 pmol/L to HER2 and 8.2 and 31 nmol/L for human and murine albumin, respectively. The radiolabeled conjugate displayed specific binding to HER2-expressing cells and good cellular retention in vitro. In vivo, fusion with ABD enabled a 25-fold reduction of renal uptake in comparison with the nonfused dimer molecule (Z(HER2:342))(2). Furthermore, the biodistribution showed high and specific uptake of the conjugate in HER2-expressing tumors. Treatment of SKOV-3 microxenografts (high HER2 expression) with 17 or 22 MBq (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) completely prevented formation of tumors, in contrast to mice given PBS or 22 MBq of a radiolabeled non-HER2-binding Affibody molecule. In LS174T xenografts (low HER2 expression), this treatment resulted in a small but significant increase of the survival time. Thus, fusion with ABD improved the in vivo biodistribution, and the results highlight (177)Lu-CHX-A''-DTPA-ABD-(Z(HER2:342))(2) as a candidate for treatment of disseminated tumors with a high level of HER2 expression. PMID:17363599

  7. Phase II study of radiopeptide {sup 177}Lu-octreotate and capecitabine therapy of progressive disseminated neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Claringbold, Phillip G. [Fremantle Hospital, Department of Oncology, Fremantle, WA (Australia); Brayshaw, Paul A.; Turner, J.H. [University of Western Australia, Department of Nuclear Medicine, Fremantle Hospital, Fremantle, WA (Australia); Price, Richard A. [Fremantle Hospital, Department of Radiology, Fremantle, WA (Australia)

    2011-02-15

    In this phase II study we investigated the safety and efficacy of combination capecitabine and {sup 177}Lu-octreotate for the treatment of disseminated, progressive, unresectable neuroendocrine tumours (NETs). Enrolled in the study were 33 patients with biopsy-proven NETs, positive {sup 111}In-octreotide scintigraphy and progressive disease measurable by CT/MRI who were to receive four cycles of 7.8 GBq {sup 177}Lu-octreotate 8-weekly, with 14 days of 1,650 mg/m{sup 2} capecitabine per day. Of the 33 patients, 25 completed four cycles. Minimal transient myelosuppression at 3-4 weeks caused grade 3 thrombocytopenia in one patient but no neutropenia. Nephrotoxicity was absent. Critical organ radiation dosimetry provided median estimates of the dose per cycle to the kidneys of 2.4 Gy and to the liver of 4.8 Gy, and showed cumulative doses all below toxic thresholds. Objective response rates (ORR) were 24% partial response (PR), 70% stable disease (SD) and 6% progressive disease. Median progression-free survival and median overall survival had not been reached at a median follow-up of 16 months (range 5-33 months). Survival at 1 and 2 years was 91% (95% CI 75-98%) and 88% (95% CI 71-96%), respectively. The addition of capecitabine radiosensitizing chemotherapy does not increase the minimal toxicity of {sup 177}Lu-octreotate radiopeptide therapy and led to an ORR of 24% PR and 70% minor response or SD in patients with progressive metastatic NETs. Tumour control and stabilization of disease was obtained in 94% of these patients. (orig.)

  8. Optimising conditions for radiolabelling of DOTA-peptides with 90Y, 111In and 177Lu at high specific activities

    International Nuclear Information System (INIS)

    DOTA-conjugated peptides, such as [DOTA0,Tyr3]octreotide (DOTATOC) and [DOTA0,Tyr3]octreotate (DOTA-tate), can be labelled with radionuclides such as 90Y, 111In and 177Lu. These radiolabelled somatostatin analogues are used for peptide receptor radionuclide therapy (PRRT). Radioligands for PRRT require high specific activities. However, although these radionuclides are produced without addition of carrier, contaminants are introduced during production and as decay products. In this study, parameters influencing the kinetics of labelling of DOTA-peptides were investigated and conditions were optimised to obtain the highest achievable specific activity. The effects of contaminants were systematically investigated, concentration dependently, in a test model mimicking conditions for labelling with minimal molar excess of DOTA-peptides over radionuclide. Kinetics of labelling of DOTA-peptides were optimal at pH 4-4.5; pH 90Y and 177Lu was completed after 20 min at 80 C, while labelling with 111In was completed after 30 min at 100 C. The effects of contaminants were systematically categorised, e.g. Cd2+ is the target and decay product of 111In, and it was found to be a strong competitor with 111In for incorporation in DOTA. In contrast, Zr4+ and Hf4+, decay products of 90Y and 177Lu, respectively, did not interfere with the incorporation of these radionuclides. The following conclusions are drawn: (a) DOTA-peptides can be radiolabelled at high specific activity; (b) reaction kinetics differ for each radionuclide; and (c) reactions can be hampered by contaminants, such as target material and decay products. (orig.)

  9. 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)

  10. Monomeric, dimeric and multimeric system of RGD peptides radiolabeled with 177Lu for tumors therapy that expressing αβ integrin s

    International Nuclear Information System (INIS)

    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 177Lu-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 177Lu-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 177Lu-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 177Lu-AuNP-c[RGDfK(C)], the 177Lu-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. 177Lu-DOTA-GGC, 177Lu- DOTA-cRGDfK and 177Lu-DOTA-E-c(RGDfK)2 were prepared by adding 177LuCl3 (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 177Lu-AuNP-c[RGDfK(C)], the MCF7 cell proliferation was significantly inhibited. Biokinetic

  11. MIRD Pamphlet No. 26: Joint EANM/MIRD Guidelines for Quantitative 177Lu SPECT Applied for Dosimetry of Radiopharmaceutical Therapy.

    Science.gov (United States)

    Ljungberg, Michael; Celler, Anna; Konijnenberg, Mark W; Eckerman, Keith F; Dewaraja, Yuni K; Sjögreen-Gleisner, Katarina; Bolch, Wesley E; Brill, A Bertrand; Fahey, Frederic; Fisher, Darrell R; Hobbs, Robert; Howell, Roger W; Meredith, Ruby F; Sgouros, George; Zanzonico, Pat; Bacher, Klaus; Chiesa, Carlo; Flux, Glenn; Lassmann, Michael; Strigari, Lidia; Walrand, Stephan

    2016-01-01

    The accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet no. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on (177)Lu (lutetium) and its application in radiopharmaceutical therapy. PMID:26471692

  12. 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.)

  13. 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.

  14. Primary investigation of dose-effect relationship of 153Sm-EDTMP in treating multiple bone metastases%153Sm-EDTMP治疗多发骨转移瘤的剂量效应关系初步观察

    Institute of Scientific and Technical Information of China (English)

    Wei Fan; Lixin Chen; Xiaowei Liu; Qiang Tang; Shengfang Zhi; Zongyuan Zeng

    2007-01-01

    Objective: To calculate the focus absorption dose of 153Sm-EDTMP with the Monte Carlo (MC) EGS4 method for treatment of bone metastases from nasopharyngeal carcinoma or breast cancer, and investigate the relationship between the focus absorption dose and painkilling effect of 153Sm-EDTMP. Methods: Four patients with multiple bone metastases from nasopharyngeal or breast carcinoma and suffered from grade Ⅳ bone pain were treated with radionuclide internal irradiation of 153Sm-EDTMP. The absorption dose and dose distribution of bone metastases and other targeted organs were calculated with MC EGS4 program based on the time-order SPECT/CT scanning and the measurement of the radioactivity in the urine accumulation. The release of bone pain and the improvement of life quality were observed. Results: Bone pain of the patients was significantly alleviated to grade Ⅱ for 3-4 weeks after internal 153Sm-EDTMP irradiation. The 3-dimensional absorption dose distribution image of bone metastases and targeted organs showed that the dose distribution in bone metastases was not asymmetrical. After injection of 0.65 × 37 MBq/kg 153Sm-EDTMP, the highest absorption dose in bone lesions was about 4.9-5.9 Gy, and the dose in the lesion margin was about 2.0 Gy. Using the highest dose as reference dose point, the relative absorption dose values of bone marrow, vertebra and sex organ near lesions were 0.48-1.1 Gy, 0.51-0.85 Gy, and 0.01-0.14 Gy, respectively. Conclusion: The absorption dose of bone metastases is significantly lower than treatment dose of 30 Gy after single irradiation of 153Sm-EDTMP. The painkilling effect is limited and in accordance with clinical observation.

  15. DNA gel electrophoretic and microaut oradiographic studies on apoptosisin bone tumor cells after exposure with 153Sm-EDTMP

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    The apoptosis in bone tumor cells is studied after 153Sm-EDTMP irradiation.Fragmented DNA is analyzed by agarose gel electrophoresis.Experimental observations show that 153Sm-EDTMP exposureinduces the internucleosomal DNA damage in bone tumor cells the DNAladder pattern formation in bone tumor cells is shown.At the same time,the microautoradiographic study indicates that 153153Sm-EDTMP could permeate through cell membrane and displays membrane-seeking condensation in bone tumor cells.Soon afterwards 153Sm-EDTMP could be phagocytized by the tumor cells and distributed in cytoplasm as well as nucleus in the form of phagosome.With the prolongation of observing time, the membrane-bounded apoptotic bodies are observed.

  16. Production of medical radioisotope 153Sm in the Tehran Research Reactor (TRR) through theoretical calculations and practical tests

    International Nuclear Information System (INIS)

    Highlights: ► Production of 153Sm isotope by neutron activation in a nuclear reactor was studied. ► Optimal parameters for weight and irradiation time were found. ► This study led to an empirical correction factor (kf). ► Kf enhanced the production procedure of the 153Sm radioisotope. ► The results led to nearly 60% decrease in the amount of material used in the production process. - Abstract: The feasibility of producing 2000–3000 mCi 153Sm by irradiation of 152Sm in 5 MW TRR was studied via TRR core simulation. In this study the cross-section of 152Sm (n,γ) 153Sm reaction from ENDF/B library was used. The effective activation cross section for production of 153Sm is obtained using the neutron spectra in different irradiation channel of the core. The activity of the simulated samples is calculated using the obtained fluxes and cross sections. Then samples were prepared and irradiated under different conditions and fluxes. The final production’s specific activity was measured by the standard dose calibrator ISOMED 1010. By comparison of the theoretical calculations and actual measurements, an empirical correction factor (Kf) was obtained, which is helpful in production procedure of the 153Sm radioisotope. The optimal weight of the samples and irradiation time was studied according to the flux calculations based on the location of the sample and saturated activity calculation. In order to test the proposed conditions, samples were prepared and were irradiated under the proposed conditions. According to the compared results with the initial irradiation condition, the new proposed sample which weighed 4 mg of Sm2O3 is acceptable for the labeling, therefore this study led to nearly 60% decrease in the amount of material used in the production process

  17. 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)

  18. Pre-Clinical Assessment of 177Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease

    Science.gov (United States)

    Ray, Geoffrey L.; Baidoo, Kwamena E.; Keller, Lanea M. M.; Albert, Paul S.; Brechbiel, Martin W.; Milenic, Diane E.

    2011-01-01

    Studies from this laboratory have demonstrated the potential of targeting HER2 for therapeutic and imaging applications with medically relevant radionuclides. To expand the repertoire of trastuzumab as a radioimmunoconjugate (RIC) vector, use of 177Lu was investigated. The combination of a 6.7 d half-life, lower energy β−-emissions (500 keV max; 130 keV ave), and an imagable γ-emission make 177Lu an attractive candidate for radioimmunotherapy (RIT) regimens for treatment of larger tumor burdens not possible with α-particle radiation. Radiolabeling trastuzumab-CHX-A″-DTPA with 177Lu was efficient with a specific binding of 60.8 ± 6.8% with HER2 positive SKOV-3 cells. Direct quantitation of tumor targeting and normal tissue uptake was performed with athymic mice bearing subcutaneous and intraperitoneal LS-174T xenografts; a peak tumor %ID/g of 24.70 ± 10.29 (96 h) and 31.70 ± 16.20 (72 h), respectively, was obtained. Normal tissue uptake of the RIC was minimal. Tumor targeting was also demonstrated by γ-scintigraphy. A therapy study administeringescalating doses of 177Lu-trastuzumab to mice bearing three day LS-174T i.p. xenografts established the effective therapeutic dose of i.p. administered 177Lu-trastuzumab at 375 μCi with a median survival of 124.5 d while a median survival of 10 d was noted for the control (untreated) group. In conclusion, trastuzumab radiolabeled with 177Lu has potential for treatment of disseminated, HER2 positive, peritoneal disease. PMID:22229017

  19. Pre-Clinical Assessment of 177Lu-Labeled Trastuzumab Targeting HER2 for Treatment and Management of Cancer Patients with Disseminated Intraperitoneal Disease

    Directory of Open Access Journals (Sweden)

    Diane E. Milenic

    2011-12-01

    Full Text Available Studies from this laboratory have demonstrated the potential of targeting HER2 for therapeutic and imaging applications with medically relevant radionuclides. To expand the repertoire of trastuzumab as a radioimmunoconjugate (RIC vector, use of 177Lu was investigated. The combination of a 6.7 d half-life, lower energy β−-emissions (500 keV max; 130 keV ave, and an imagable γ-emission make 177Lu an attractive candidate for radioimmunotherapy (RIT regimens for treatment of larger tumor burdens not possible with α-particle radiation. Radiolabeling trastuzumab-CHX-A″-DTPA with 177Lu was efficient with a specific binding of 60.8 ± 6.8% with HER2 positive SKOV-3 cells. Direct quantitation of tumor targeting and normal tissue uptake was performed with athymic mice bearing subcutaneous and intraperitoneal LS-174T xenografts; a peak tumor %ID/g of 24.70 ± 10.29 (96 h and 31.70 ± 16.20 (72 h, respectively, was obtained. Normal tissue uptake of the RIC was minimal. Tumor targeting was also demonstrated by γ-scintigraphy. A therapy study administering escalating doses of 177Lu-trastuzumab to mice bearing three day LS-174T i.p. xenografts established the effective therapeutic dose of i.p. administered 177Lu-trastuzumab at 375 μCi with a median survival of 124.5 d while a median survival of 10 d was noted for the control (untreated group. In conclusion, trastuzumab radiolabeled with 177Lu has potential for treatment of disseminated, HER2 positive, peritoneal disease.

  20. 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.

  1. 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.

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

    Science.gov (United States)

    Yong, Kwon Joong; Milenic, Diane E.; Baidoo, Kwamena E.; Brechbiel, Martin W.

    2016-01-01

    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. PMID:27196891

  3. 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.)

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

    International Nuclear Information System (INIS)

    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 [90Y]DOTA-TATE and [177Lu]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 (90Y) and a medium-energy beta/gamma emitter (177Lu) 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 [177Lu]DOTA-TATE (5.55 GBq) and [90Y]DOTA-TATE (2.6 GBq). A dosimetric evaluation was carried out after administration of [177Lu]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 [90Y]DOTA-TATE and [177Lu]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 [90Y]DOTA-TATE and [177Lu]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.)

  5. 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

  6. Synthesis, stabilization and formulation of [177Lu]Lu-AMBA, a systemic radiotherapeutic agent for Gastrin Releasing Peptide receptor positive tumors

    International Nuclear Information System (INIS)

    A robust formulation was developed for [177Lu]Lu-AMBA (177Lu-DO3A-CH2CO-G-[4-aminobenzoyl]-QWAVGHLM-NH2), a Bombesin-like agonist with high affinity for Gastrin Releasing Peptide (GRP) receptors. During optimization of labeling, the effect of several radiostabilizers was evaluated; a combination of selenomethionine and ascorbic acid showed superiority over other tested radiostabilizers. The resulting two-vial formulation maintains a radiochemical purity (RCP) of >90% for at least 2 days at room temperature. The method of stabilization should be useful for other methionine-containing peptide radiopharmaceuticals in diagnostic and therapeutic applications

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

    International Nuclear Information System (INIS)

    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 177Lu. 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 177Lu-labelled antibodies, in vivo biodistribution experiments were performed. For radioimmunotherapy (RIT) studies, non-obese diabetic recombination activating gene-1 (NOD-Rag1null) interleukin-2 receptor common gamma chain (IL2r γ null) null mice (NRG mice) were xenografted subcutaneously with Raji Burkitt's lymphoma cells. 177Lu-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 177Lu-labelled anti-CD22 IgG than of 177Lu-labelled rituximab. Treatment with 177Lu-conjugated huRFB4 resulted in increased tumour growth inhibition and significantly longer survival than treatment with 177Lu-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 177Lu-based CD22-specific RIT in combination with rituximab is a promising new treatment option for refractory B-NHL. (orig.)

  8. Optimization of the preparation of 153Sm - EDTMP using natural samarium targets for clinical use

    International Nuclear Information System (INIS)

    153Sm (specific activity 3.7 to 5.55 GBq/mg) was produced by irradiating natural Sm2O3 at a flux of 2.2 x 1013 n x cm-2 x s-1. Ethylenediaminetetramethylenephosphonate (EDTMP) was synthesised according to a reported method. Complexation was carried out by varying experimental parameters such as mole ratios of metal to ligand, pH, time and temperature of reaction to obtain quantitative yields. The radiochemical purity of the complex was assessed by various analytical techniques including HPLC. In vitro ligand exchange studies were undertaken to ensure suitability of the product for therapy. Biodistribution studies were carried out in Wistar rats and adequate bone uptake, retention and rapid clearance from blood stream were observed. (author)

  9. Preparation of DOTA-TATE and DOTA-NOC freeze-dried kits for formulation of patient doses of 177Lu-labeled agents and their comparison for peptide receptor radionuclide therapy application

    International Nuclear Information System (INIS)

    The objective of the present work is to prepare freeze-dried DOTA-TATE and DOTA-NOC kits for the easy and convenient preparation of patient doses of 177Lu-DOTA-TATE and 177Lu-DOTA-NOC, respectively at the hospital radiopharmacy and to compare the radio-peptides with respect to their radiochemical and biological behaviors. Freeze-dried kits of DOTA-TATE and DOTA-NOC, comprising a lyophilized mixture of 200 μg of DOTA-peptide, 80 mg of gentisic acid and 13.9 mg of ammonium acetate were prepared. Therapeutic doses of 177Lu-labeled peptides (up to 200 mCi, 7.4 GBq) were prepared using these kits and 177Lu, produced in-house, with >99 % radiochemical purity and high stability following an easy and convenient protocol. Comparative pharmacokinetic behavior of the radio-peptides was studied by carrying out biodistribution studies in normal Wistar rats which revealed higher retention of activity in several major organs and slower renal clearance for 177Lu-DOTA-NOC compared to that of 177Lu-DOTA-TATE. Preliminary pharmacokinetic studies, carried out in limited number of patients suffering from cancers of neuroendocrine origins, showed lower accumulation of activity in vital organs and faster renal clearance of 177Lu-DOTA-TATE compared to that of 177Lu-DOTA-NOC. (author)

  10. Comparative study on DOTA-derivatized bombesin analog labeled with 90Y and 177Lu: in vitro and in vivo evaluation

    International Nuclear Information System (INIS)

    Introduction: The aim of the study was to compare in vitro and in vivo a novel DOTA-chelated bombesin (BN) analog of the amino acid sequence, QRLGNQWAVGHLM-CONH2 (BN[2-14]NH2), labeled with 90Y and 177Lu, for its potential use in targeted radiotherapy of tumors expressing gastrin releasing peptide (GRP) receptors. The same amino acid sequence, but with different chelator, referred as BN1.1 (Gly-Gly-Cys-Aca-QRLGNQWAVGHLM-CONH2), has already been studied and reported; however, the DOTA-chelated one, suitable for labeling with M+3 type radiometals, was not yet described. Methods: The conditions for labeling of DOTA-BN[2-14]NH2 with noncarrier added 90Y and with 177Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide 90Y-DOTA-BN[2-14]NH2 and 177Lu-DOTA-BN[2-14]NH2 of high SA. The stability of the radiolabeled compounds in human serum was evaluated over a period of 24 h. The human prostate cancer cell line PC-3, known to express GRP receptors, was used for in vitro evaluation of radiolabeled peptide affinity to GRP receptors and for assessment of cytotoxicity of both nonlabeled and radiolabeled peptide. Biodistribution accompanied by receptor blocking was studied in normal Swiss mice. Results: 90Y-DOTA-BN[2-14]NH2 and 177Lu-DOTA-BN[2-14]NH2 were obtained with radiochemical yield >98% and high SA (67.3 GBq 90Y/μmol and 33.6 GBq 177Lu/μmol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH2 and both natY- and natLu-labeled analogs to GRP receptors were high (IC50=1.78, 1.99, and 1.34 nM, respectively), especially for the natLu-DOTA-BN[2-14]NH2 complex. The cytotoxicity study of DOTA-BN[2-14]NH2 to PC-3 cells revealed an IC50=6300 nM after 72 h of exposition, while the labeled derivatives showed no significant cytotoxic effect. The internalization rate to PC-3 cells was more rapid for 177Lu-labeled peptide (84.87%) than for the 90Y-labeled one (80.79%), while the efflux

  11. 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

  12. 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.)

  13. 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

  14. Biological distribution of 51Cr-heparin

    International Nuclear Information System (INIS)

    The kinetics of heparin in normal Wistar rats using the radioactive tracer 51Cr, has been studied. The labeled and purified 51Cr-heparin was injected into rats intravenously and by intraperitoneal injection. In measuring the radioactivity of organs it was possible to conclude that the tissues rich in mast cells, liver and spleen, were found to take up the greater amounts of heparin. The curve that represents the logarithm of the concentration of heparin versus time is biexponential. The half-lives of the two exponential were determined. The volume of distribution, the rate constant and the renal clearance were determined by the values of the plasma levels and urinary excretions. The biological half-time, the turnover rate and the turnover time were determined by measuring the residual radioactivity of the total body and urinary excretions. With the data obtained from the mentioned experiments a compartmental model was performed in which the plasma is the central compartment for the distribution of the drug, exchanging with another extraplasmatic compartment and finally the drug being stored in reticulo endothelial system cells. (Author)

  15. Radiolabelled of c-DOTA-RGD and c-DOTA-RGDf with 177Lu and evaluation in vitro and in vivo stability

    International Nuclear Information System (INIS)

    Integrin αvβ3 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 αvβ3 integrin. The aim of this study was to label c-DOTA-RGD and c-DOTA-RGDf peptides with 177Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of 177LuCl3 with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90o 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 αvβ3) 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. 177Lu-DOTA-RGD and 177Lu-DOTA-RGDf were obtained with radiochemical purities > 95%, showing adequate in vitro and in vivo stability and specific binding to □v□3 receptors. (Author)

  16. 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...

  17. 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.

  18. 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

  19. Comparison of 90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer

    International Nuclear Information System (INIS)

    90Y/177Lu labeled DOTA-Bz-RGD tetramer and DOTA-RGD tetramer were prepared, and the effect of Bz-DOTA and DOTA on labeling conditions and in vitro stability of radiolabeled compounds was compared. The labeling conditions, including reaction pH, reaction temperature and reaction time, were investigated. ITLC and HPLC show that the labeling yields of four radiolabeled compounds are more than 95% under optimal conditions (pH=6.0, reacting at 100 degree C for 15-20 min); the four radiolabeled compounds show pretty good stability in saline and fetal bovine serum. Although introducing of Bz has no effect on labeling conditions and in vitro stability of radiolabeled compounds, it brings a little change on molecule polarity. HPLC analysis and lg P values reveal that introducing of Bz increases the lipophilicity of radiolabeled compounds. (authors)

  20. 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

  1. 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.)

  2. Synthesis, analysis, purification and biodistribution in an animal model of radiopharmaceutical 177Lu3+ -dotatato for diagnostic and therapeutic use in neuroendocrine tumors

    International Nuclear Information System (INIS)

    The aim of this work was to propose rationalization in the synthesis, analysis and purification of radiopharmaceutical 177 Lu3+ - 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 177Lu3+: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 : 26μg) for that from the Oak Ridge National Laboratory /USA, and 1:16 (370 MBq: 11.8 μg) 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 177Lu3+ - DOTATATO permits high economy in production costs. Chemical studies on the synthesis of radiopharmaceuticals also placed in evidence the interference of 177Hf4+, the decay product of 177Lu3=, as the 177 Lu3= 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. 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.)

  4. 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.

  5. Somatostatin-receptor-targeted {alpha}-emitting {sup 213}Bi is therapeutically more effective than {beta}{sup -}-emitting {sup 177}Lu in human pancreatic adenocarcinoma cells

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Tapan K. [Radiopharmaceutical Sciences Program, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001 (United States); Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, NM 87131 (United States); Norenberg, Jeffrey P. [Radiopharmaceutical Sciences Program, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001 (United States)]. E-mail: jpnoren@unm.edu; Anderson, Tamara L. [Radiopharmaceutical Sciences Program, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001 (United States); Prossnitz, Eric R. [Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, NM 87131 (United States); Stabin, Michael G. [Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232 (United States); Atcher, Robert W. [Radiopharmaceutical Sciences Program, College of Pharmacy, University of New Mexico, Albuquerque, NM 87131-0001 (United States); Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States)

    2007-02-15

    Introduction: Advance clinical cancer therapy studies of patients treated with somatostatin receptor (sstr)-targeted [DOTA{sup 0}-Tyr{sup 3}]octreotide (DOTATOC) labeled with low-linear-energy-transfer (LET) {beta}{sup -}-emitters have shown overall response rates in the range of 15-33%. In order to improve outcomes, we sought to compare the therapeutic effectiveness of sstr-targeted high-LET {alpha}-emitting {sup 213}Bi to that of low-LET {beta}{sup -}-emitting {sup 177}Lu by determining relative biological effectiveness (RBE) using the external {gamma}-beam of {sup 137}Cs as reference radiation. Methods: Sstr-expressing human pancreatic adenocarcinoma Capan-2 cells and A549 control cells were used for this study. The effects of different radiation doses of {sup 213}Bi and {sup 177}Lu labeled to 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid and sstr-targeted DOTATOC were investigated with a clonogenic cell survival assay. Apoptosis was measured using the Cell Death Detection ELISA{sup PLUS} 10x kit. Results: Using equimolar DOTATOC treatment with concurrent irradiation with a {sup 137}Cs source as reference radiation, the calculated RBE of [{sup 213}Bi]DOTATOC was 3.4, as compared to 1.0 for [{sup 177}Lu]DOTATOC. As measured in terms of absorbance units, [{sup 213}Bi]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [{sup 177}Lu]DOTATOC at the final treatment time of 96 h (P<.001) in sstr-expressing Capan-2 cells. Conclusions: In conclusion, at the same absorbed dose, [{sup 213}Bi]DOTATOC is therapeutically more effective in decreasing survival than is [{sup 177}Lu]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE.

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

    International Nuclear Information System (INIS)

    The purpose of this study was to evaluate the efficacy and safety of 177Lu-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 177Lu-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 177Lu-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 177Lu-EDTMP was found to be a safe and effective radiopharmaceutical for bone pain palliation in patients with metastatic prostate and breast carcinoma. There were no differences in efficacy or toxicity between patients receiving low-dose and high-dose 177Lu-EDTMP. (orig.)

  7. 153 SM-EDTMP (Samario como tratamiento del dolor óseo de origen metastático 153 SM-EDTMP (SAMARIO For the treatment of metastatic bone pain

    Directory of Open Access Journals (Sweden)

    A. B. de la Calle

    2006-04-01

    Full Text Available Introducción: 153 Sm-EDTMP es un agente radioactivo que puede ser usado para el diagnóstico así como el tratamiento de algunas enfermedades. El objetivo de este estudio es evaluar la eficacia de 153 Sm-EDTMP en el tratamiento del dolor crónico debido a metástasis óseas en el cáncer de próstata. Material y métodos: Se realiza un estudio prospectivo dónde se incluyen siete pacientes con dolor crónico, en relación con metástasis óseas por cáncer prostático, a los que se les administra de forma intravenosa 153 Sm-EDTMP para controlar el dolor. La eficacia de este agente fue evaluada según los cambios obtenidos en la escala visual-analgésica de (EVA, tiempo en el que se alcanzó la respuesta terapéutica, efectos adversos y cambios en el consumo diario de analgésicos. Resultados: 2 de 7 pacientes (28.5% tuvieron remisión completa del dolor, 4 de 7 (37.2% remisión parcial (EVA ≥1 y ≤3 y 1 de 7 (14.3% no mostraron mejoría. La respuesta terapéutica ocurrió a los 10-30 días después de la administración del fármaco en 83.3% de los pacientes, 16.6% requirieron más tiempo. No se observaron efectos adversos mayores; 20% sintieron nauseas, 5% vómitos y 0% toxicidad hematológica. 5 de 7 pacientes (71.4% redujeron el consumo de analgésicos. Conclusiones: 153 Sm-EDTMP es seguro y eficaz para la paliación rápida del dolor ocasionado por metástasis óseas, aunque aún quedan importantes cuestiones que resolver, fundamentalmente sobre los factores que influyen en la respuesta terapéutica a este radiofármaco.Introduction: 153 Sm-EDTMP is a radioactive agent used for both the diagnosis and treatment of some diseases. The aim of this study is to evaluate the efficacy of 153 Sm-EDTMP for the treatment of chronic pain due to bone metastasis in prostate cancer. Material and methods: Prospective study including seven patients suffering chronic pain due to bone metastasis in prostate cancer to whom intravenous 153 Sm-EDTMP for pain

  8. 153Sm -DOTA-phosphine-ruthenium and gold bimetallic complexes as new radio-theranostics

    International Nuclear Information System (INIS)

    Full text of publication follows. Since the pioneer discovery of cisplatin for biological applications by Rosenberg in the 1960's [Ref.1] metal complexes have become the most currently investigated and used class of compounds in cancer chemotherapy [Ref.2]. However in most cases, their mechanisms of action are still poorly understood. Imaging drugs aimed at understanding their mechanism of action and studying their pharmacokinetics is thus one of the key challenges of medicinal chemists today. To take up this challenge new DOTA-phosphine compounds were synthesized. It is a versatile tool to image organometallic complexes, and allowed the access to an unprecedented family of theranostics featuring Au and Ru complexes for the therapeutic moiety and 153Sm for the imaging part. The radiolabelling of the ligand was studied and the stability of corresponding complexes was evaluated. Their cytotoxicity was also tested on cancer cells, and their biodistribution was determined in vivo. References: [1] Rosenberg, B.; VanCamp, L.; Krigas, T., Inhibition of Cell Division in Escherichia coli by Electrolysis Products from a Platinum Electrode, Nature 1965, 205, 698-699; [2] Zhang, C. X.; Lippard, S. J., New metal complexes as potential therapeutics, Curr. Opin. Chem. Biol. 2003, 7, 481-489. (authors)

  9. Development of a {sup 186}Re-HEDP formulation and radio pharmacokinetics comparison with {sup 153}Sm-EDTMP; Desarrollo de una formulacion de {sup 186}Re-HEDP y comparacion radiofarmacocinetica con el {sup 153}Sm-EDTMP

    Energy Technology Data Exchange (ETDEWEB)

    Bribiesca C, A.I

    1998-12-01

    Because of the growing interest in the use of the beta emitters radiopharmaceuticals applied to therapy in different cancer cases, we developed a formulation of {sup 186} Re-HEDP (hydroxy ethylidene diphosphonate) as a pain palliative in osseous metastases. Besides serving like therapeutic agent, together with the {sup 153} Sm-EDTMP (ethylene diamine tetra methylene phosphonate), which has already been synthesized and proved, labels EHDP could be very useful like a diagnostic agent in the pursuit of the illness. The irradiation conditions for Rhenium-186 were established by ORIGIN 2 codes for TRIGA reactors. A pharmaceutical formulation was developed employing a factorial experimental design obtaining a complex with a radiochemical purity over 90 %. The complexes {sup 186} Re-HEDP {sup 153} Sm-EDTMP were intravenous administered in BALB-C mice sacrifying them in several intervals of time in order to determine the cumulated activity in each organ to perform absorbed dose calculation by MIRD methodology (Medical Internal Radiation Dose). Radio pharmacokinetic data demonstrated that both complexes follow a biexponential kinetic of first order behavior. In the case of the {sup 186} Re-HEDP the value of the {alpha} constant was 0.2789 and {beta} 0.0006 with an effective dose of 2.56 (mSv)/MBq , while for the complex {sup 153} Sm-EDTMP the values of {alpha} to and {beta} were 0.9012 and and 0.616 respectively and the effective dose was 0.262 (mSv)/MBq. In conclusion, radiopharmaceutical {sup 153} Sm-EDTMP, showed a greater bone uptake and a minor effective dose, for which it is a better radiopharmaceutical, respect to with the formulation of {sup 186} Re-HEDP. (Author)

  10. Application of a wrist dosimeter prototype for radiation monitoring ({sup 153}Sm) during a therapeutic procedure simulation

    Energy Technology Data Exchange (ETDEWEB)

    Cecatti, S G P [Fundacentro, Ministerio do Trabalho e Emprego, Rua Capote Valente, 710, 05409-002, Sao Paulo (Brazil); Guimaraes, M I C C [Centro de Medicina Nuclear, Universidade de Sao Paulo, Travessa da Rua Dr. Ovidio Pires de Campos s/n, 05403-010, Sao Paulo (Brazil); Caldas, L V E [Instituto de Pesquisas Energeticas e Nucleares, IPEN-Comissao Nacional de Energia Nuclear, Avenida Professor Lineu Prestes, 2242, 05508-000, Sao Paulo (Brazil)], E-mail: scecatti@fundacentro.gov.br, E-mail: ines@hcnet.usp.br, E-mail: lcaldas@ipen.br

    2009-12-01

    Gamma and beta radiation emitting radiopharmaceuticals are handled in nuclear medicine services, and in many cases there is only individual monitoring of gamma radiation. In this paper, the results obtained using a wrist dosimeter prototype (CaSO{sub 4}:Dy+Teflon pellets) show that the doses for workers occupationally exposed to beta radiation from {sup 153}Sm are not negligible. It is important that this dose is evaluated, and it has to be taken into consideration in the individual monitoring system.

  11. Development of a 186Re-HEDP formulation and radio pharmacokinetics comparison with 153Sm-EDTMP

    International Nuclear Information System (INIS)

    Because of the growing interest in the use of the beta emitters radiopharmaceuticals applied to therapy in different cancer cases, we developed a formulation of 186 Re-HEDP (hydroxy ethylidene diphosphonate) as a pain palliative in osseous metastases. Besides serving like therapeutic agent, together with the 153 Sm-EDTMP (ethylene diamine tetra methylene phosphonate), which has already been synthesized and proved, labels EHDP could be very useful like a diagnostic agent in the pursuit of the illness. The irradiation conditions for Rhenium-186 were established by ORIGIN 2 codes for TRIGA reactors. A pharmaceutical formulation was developed employing a factorial experimental design obtaining a complex with a radiochemical purity over 90 %. The complexes 186 Re-HEDP 153 Sm-EDTMP were intravenous administered in BALB-C mice sacrifying them in several intervals of time in order to determine the cumulated activity in each organ to perform absorbed dose calculation by MIRD methodology (Medical Internal Radiation Dose). Radio pharmacokinetic data demonstrated that both complexes follow a biexponential kinetic of first order behavior. In the case of the 186 Re-HEDP the value of the α constant was 0.2789 and β 0.0006 with an effective dose of 2.56 (mSv)/MBq , while for the complex 153 Sm-EDTMP the values of α to and β were 0.9012 and and 0.616 respectively and the effective dose was 0.262 (mSv)/MBq. In conclusion, radiopharmaceutical 153 Sm-EDTMP, showed a greater bone uptake and a minor effective dose, for which it is a better radiopharmaceutical, respect to with the formulation of 186 Re-HEDP. (Author)

  12. Incremental value of metabolic radiotherapy of bone metastases with 153Sm-EDTMP in prostate cancer. About 67 cases

    International Nuclear Information System (INIS)

    Full text of publication follows. Introduction: painful bone metastases are common in advanced prostate cancer. Samarium-153-ethylenediaminetetra-methylenephosphonic acid (153Sm-EDTMP; Quadramet) is a beta-particles emitter that concentrates in the areas of enhanced osteoblastic activity and used for palliate pain from bone metastases. Our purpose is to evaluate the incremental value of the 153Sm-EDTMP, in patients affected of cancer of the prostate with painful bony metastasis. Methods: 67 patients with metastatic prostate cancer received a single bolus infusion of 153Sm (37 MBq/kg). All patients had painful bone metastases to more than one anatomical region. Bone specific pain, analgesic score, and blood count were evaluated before and after treatment with a receding of 38 months. Results: we observed a positive answer in 85% of the cases; this answer was complete in 35% of the cases. The results gotten after multiple administrations show that the cures could be repeated with results comparable to those of the first cure. The therapeutic efficiency is at least equivalent to those of the other therapeutic means, with nearly non-existent secondary effects. The only toxicity is of hematological order; it is the most often moderate and reversible with a complete recuperation at the end of 8 weeks. Besides, the effect on the pain came with an improvement of the quality of life of the patients treaties. Conclusion: due to its half-life of 46 hours and its beta emissions, a high dose rate of 153Sm can be delivered to regions adjacent to enhanced osteoblastic activity over a short period of time with little residual long term activity being left in the bone marrow. Its administration to patients with prostate cancer suffering from painful bone metastases that enhance on bone scans, offered clinical relevant pain relief with tolerable hematological toxicity and then enjoy a better quality of life. (authors)

  13. 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

  14. Design and optimization of the production process of radiopharmaceutical 177Lu-DOTA-Nal3-Octreotide for the treatment of gastro-entero-pancreatic tumors

    International Nuclear Information System (INIS)

    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 Nal3-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 (177Lu) 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 177Lu-DOTA-Nal3-Octreotide (177Lu-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 177Lu-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 177Lu, 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 Instituto Nacional de Investigaciones

  15. Evaluation of genotoxic and cytotoxic effects of 153 Sm-EDTMP in peripheral blood lymphocytes of bone metastasis patients

    International Nuclear Information System (INIS)

    In this study the cellular damage in peripheral lymphocytes after exposure to 153 Sm-EDTMP (Samarium-153 ethylene-diamine-tetramietylene-phosphonate) was determined using the technique of micronuclei analysis and differential coloration.153 Sm-EDTMP is a radiopharmaceutical used for pain relief in patients with bone metastases. The analysis of the frequency of micronuclei in patient blood samples obtained one hour after endovenous administration of radiopharmaceutical (41 MBq/kg) showed no statistical difference in relation to basal values in binucleated cells. However the analysis of damage distribution in mononucleated cells, showed that the patients without previous radiotherapy treatment presented a significant increase in the frequency of cells with one micronucleus and in those who had taken previous radiotherapy treatment, in cells with two or more micronuclei. The in vitro experiments conducted with the exposition of total blood to three radiation concentrations of 153 Sm-EDTMP (0.370, 0.555 and 1.110 MBq/mL) during one hour showed an increase in the frequency of micronuclei and necrotic and apoptotic cells with increasing radiation dose. Dose-response curves for healthy donors and patients with bone metastasis without previous radiotherapy treatment were constructed. The comparison of the curves showed that patients presented higher radiosensitivity, either micronuclei or dead cell (necrotic or apoptotic) percentages, than healthy donors. (author)

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

    International Nuclear Information System (INIS)

    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 177Lu-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 177Lu-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 99mTc-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. Variables linked

  17. Radiotherapeutic efficacy of 153Sm-CMDTPA-Tyr3-octreotate in tumor-bearing rats

    International Nuclear Information System (INIS)

    A number of radiolabeled somatostatin analogs have been evaluated in animal tumor models for radiotherapeutic efficacy. The majority of the agents tested have used either high-energy beta-emitters, such as Y-90 or Re-188, or the Auger electron-emitting radionuclide, In-111. Because a medium-energy beta-emitter might have equivalent efficacy compared to high-energy emitters, and lower toxicity to non-target tissues, we have evaluated the therapeutic potential of the beta-emitting nuclide, Sm-153, chelated to the somatostatin analog, CMDTPA-Tyr3-octreotate. Using an in vitro binding assay, this octreotate derivative was shown to have high affinity for the somatostatin subtype-2 receptor (IC50 = 2.7 nM). Biodistribution studies in CA20948 tumor-bearing Lewis rats demonstrate that the Sm-153 labeled compound has high uptake and retention in tumor tissue (1.7% injected dose/g tissue, 4 hrs post injection) and has rapid overall clearance properties from non-target tissue. Radiotherapy studies were carried out using 153Sm-CMDTPA-Tyr3-octreotate and CA20948 tumor bearing Lewis rats at 7 days post implant. Dose regimens consisting of single and multiple i.v. injections of 5.0 mCi/rat (185 MBq) were employed over a time span of 7 days. Suppression of tumor growth rate was observed in all treated animals compared to untreated controls. Greater inhibition of tumor growth was observed in animals that received multiple doses. These studies indicate that medium-energy beta-emitting isotopes have considerable potential for the treatment of somatostatin receptor-positive tumors

  18. 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

  19. Lessons on Tumour Response: Imaging during Therapy with 177Lu-DOTA-octreotate. A Case Report on a Patient with a Large Volume of Poorly Differentiated Neuroendocrine Carcinoma

    Directory of Open Access Journals (Sweden)

    Ulrike Garske, Mattias Sandström, Silvia Johansson, Dan Granberg, Hans Lundqvist, Mark Lubberink, Anders Sundin, Barbro Eriksson

    2012-01-01

    Full Text Available Favourable outcomes of peptide receptor radiotherapy (PRRT of neuroendocrine tumours have been reported during the last years. Still, there are uncertainties on the radionuclides to be used, the treatment planning, and the indication in patients with a high proliferation rate.This case report describes a patient with a high tumour burden of poorly differentiated neuroendocrine carcinoma of unknown primary with a proliferation rate in liver metastases up to 50%, undergoing fractionated treatment with 7 cycles of 177Lu-DOTA-octreotate (7.4 GBq each after disease progression on two different chemotherapy regiments. Based on initial staging scintigraphy, somatostatin receptor expression was very high.Longitudinal dosimetry studies during therapy indicated ongoing increases in tumour-to-organ ratios that coincided with an objective response.We conclude that fractionated therapy with 177Lu-DOTA-octreotate should be considered a treatment option also for those patients with large tumours, high proliferation, and high receptor expression.

  20. Sci—Thur AM: YIS - 03: irtGPUMCD: a new GPU-calculated dosimetry code for {sup 177}Lu-octreotate radionuclide therapy of neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Montégiani, Jean-François; Gaudin, Émilie; Després, Philippe [Physics, Engineering Physics and Optics, Université Laval, Quebec City, QC (Canada); Jackson, Price A. [Molecular Imaging and Targeted Therapeutics, Peter MacCallum Cancer Centre, Melbourne, VIC (Australia); Beauregard, Jean-Mathieu [Radiology, Université Laval, Quebec City, QC (Canada)

    2014-08-15

    In peptide receptor radionuclide therapy (PRRT), huge inter-patient variability in absorbed radiation doses per administered activity mandates the utilization of individualized dosimetry to evaluate therapeutic efficacy and toxicity. We created a reliable GPU-calculated dosimetry code (irtGPUMCD) and assessed {sup 177}Lu-octreotate renal dosimetry in eight patients (4 cycles of approximately 7.4 GBq). irtGPUMCD was derived from a brachytherapy dosimetry code (bGPUMCD), which was adapted to {sup 177}Lu PRRT dosimetry. Serial quantitative single-photon emission computed tomography (SPECT) images were obtained from three SPECT/CT acquisitions performed at 4, 24 and 72 hours after {sup 177}Lu-octreotate administration, and registered with non-rigid deformation of CT volumes, to obtain {sup 177}Lu-octreotate 4D quantitative biodistribution. Local energy deposition from the β disintegrations was assumed. Using Monte Carlo gamma photon transportation, irtGPUMCD computed dose rate at each time point. Average kidney absorbed dose was obtained from 1-cm{sup 3} VOI dose rate samples on each cortex, subjected to a biexponential curve fit. Integration of the latter time-dose rate curve yielded the renal absorbed dose. The mean renal dose per administered activity was 0.48 ± 0.13 Gy/GBq (range: 0.30–0.71 Gy/GBq). Comparison to another PRRT dosimetry code (VRAK: Voxelized Registration and Kinetics) showed fair accordance with irtGPUMCD (11.4 ± 6.8 %, range: 3.3–26.2%). These results suggest the possibility to use the irtGPUMCD code in order to personalize administered activity in PRRT. This could allow improving clinical outcomes by maximizing per-cycle tumor doses, without exceeding the tolerable renal dose.

  1. 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.

  2. {sup 177}Lu-labeled-VG76e monoclonal antibody in tumor angiogenesis: a comparative study using DOTA and DTPA chelating systems

    Energy Technology Data Exchange (ETDEWEB)

    Fani, M.; Psimadas, D. [Inst. of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' ' Demokritos' ' , Athens (Greece); Biomedica Life Sciences S.A., Athens (Greece); Bouziotis, P.; Gourni, E.; Varvarigou, A.D. [Inst. of Radioisotopes and Radiodiagnostic Products, National Centre for Scientific Research ' ' Demokritos' ' , Athens (Greece); Harris, A.L. [Weatherall Inst. of Molecular Medicine, Cancer Research U.K., Univ. of Oxford (United Kingdom); Loudos, G. [Biomedical Simulations and Imaging Lab., National Technical Univ. of Athens (Greece); Maecke, H.R. [Div. of Radiological Chemistry, Univ. Hospital Basel (Switzerland)

    2007-07-01

    Vascular endothelial growth factor (VEGF) is one of the molecules which regulate angiogenesis, a phenomenon observed in many diseases, including cancer. VG76e, an anti-VEGF monoclonal antibody, was labeled with {sup 177}Lu via p-SCN-Bz-DOTA and CHX-A''-DTPA chelating systems, in order to investigate its possible therapeutic use. Labeling was performed by a 30 min incubation of {sup 177}LuCl{sub 3} and each immunoconjugate, at 37 C. Radiochemical analysis showed the formation of a single radioactive species, at a yield higher than 98%, for both immunoconjugates. Kits have been formulated for both VG76e-DOTA and VG76e-DTPA. Stability studies, in the presence of a competitor excess, showed that both radiolabeled species remained sufficiently stable (95%) for at least 48 h. Biodistribution results in normal mice were similar for both radioimmunoconjugates, with no significant bone uptake. Gamma camera images of tumor-bearing mice showed satisfactory visualization of the tumor 24 h p.i., while a higher uptake was observed at 48 h p.i. Our findings indicate that both the bifunctional chelating agents p-SCN-Bz-DOTA and CHX-A''-DTPA can be used for the labeling of VG76e with {sup 177}Lu, with high labeling yield and stability. Their in vivo behaviour in normal and tumor-bearing mice looks promising and they can be successfully used for tumor imaging studies. (orig.)

  3. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide

    International Nuclear Information System (INIS)

    The aim of this retrospective study was to determine whether patients with previous peptide receptor radionuclide therapy using high-activity 111In-pentetreotide can be safely treated with 177Lu-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) 177Lu-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 111In-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 177Lu-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 177Lu-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. 177Lu-octreotate is a safe and well-tolerated therapy for patients who have previously been treated with 111In-pentetreotide and can be safely combined with radiosensitising

  4. {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

  5. {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

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

    International Nuclear Information System (INIS)

    The proposition of uPAR as a potential target in cancer therapy is advanced by its predominant expression at the invasive front of colorectal cancer (CRC) and its value as prognostic biomarker for poor survival in this disease. In this study, we provide the first in vivo proof-of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. Methods: A 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 cells were inoculated in Nude mice and treated with 177Lu-DOTA-AE105 once a visible tumor had formed. To evaluate the true effect of the targeted radiotherapy, two controls groups were included in this study, one receiving a 177Lu-labeled non-binding control peptide and one receiving vehicle. All animals were treated day 0 and 7. A parallel 18F-FLT PET/CT study was performed on day 0, 1, 3 and 6. Dosimetry calculations were based on a biodistribution study, where organs and tissue of interest were collected 0.5, 1.0, 2.0, 4.0 and 24 h post injection of 177Lu-DOTA-AE105. Toxicity was assessed by recording mouse weight and by H and E staining of kidneys in each treatment group. Results: uPAR-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 18F-FLT PET/CT imaging study revealed a significant correlation between 18F-FLT tumor uptake and efficacy of the radionuclide therapy. A histological examination of the kidneys from one animal in each treatment group did not reveal any gross abnormalities and the general performance of all treated animals also showed no indications of radioactivity-induced toxicity. Conclusion: These findings document for the

  7. Chemical and biological evaluation of {sup 153}Sm and {sup 46/47}Sc complexes of indazolebisphosphonates for targeted radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Neves, Maria, E-mail: mneves@itn.p [Instituto Tecnologico e Nuclear, Sacavem (Portugal); Teixeira, Fatima C.; Antunes, Ines [INETI-Departamento de Tecnologia de Industrias Quimicas, Lisboa (Portugal); Majkowska, Agnieszka [Institute of Nuclear Chemistry and Technology, Warsaw (Poland); Gano, Lurdes [Instituto Tecnologico e Nuclear, Sacavem (Portugal); Santos, Ana Cristina [IBB-Instituto de Biofisica e Biomatematica, Coimbra (Portugal)

    2011-01-15

    Introduction: Novel 1-hydroxy-1,1-bisphosphonates derived from indazole and substituted at the C-3 position were labeled with the radionuclides {sup 46}Sc and {sup 153}Sm. Several parameters such as molar ligand concentration, pH, reaction time and temperature were studied. The radiolabelling yield, reaction kinetics and stability were assessed and radiocomplexes were evaluated by in vitro and in vivo experiments. Methods: The radionuclides {sup 46}Sc and {sup 153}Sm were obtained by neutron irradiation of natural Sc{sub 2}O{sub 3} and enriched {sup 152}Sm{sub 2}O{sub 3} (98.4%) targets at the neutron flux of 3x10{sup 14} n cm{sup -2} s{sup -1}. The radiolabelling yield, reaction kinetics and stability were accomplished by ascending instant thin layer chromatography. The radiocomplexes were submitted to in vitro experiments (hydroxyapatite binding and lipophilicity) and biodistribution studies in animal models. Results: The radionuclides {sup 46}Sc and {sup 153}Sm were produced with specific activities of 100 and 430 MBq mg{sup -1}, respectively. High radiochemical yields were achieved and the hydrophilic radiocomplexes have shown high degree of binding to hydroxyapatite. Biodistribution studies at 1, 3 and 24 h of the 4 radiocomplexes under study, have showed a similar biodistribution profile with a relatively high bone uptake, slow clearance from blood and a very slow rate of total radioactivity excretion from the whole animal body. Conclusion: We have developed a new class of indazolebisphosphonates complexes with radioisotopes of samarium and scandium. All complexes have shown high degree of binding to hydroxyapatite, which could be attributed to the ionized phosphonate groups. The bone uptake and the bone-to-muscle ratios were relatively low.

  8. 153Sm3+ and 111In3+ DTPA derivatives with high hepatic specificity: in vivo and in vitro studies

    OpenAIRE

    Prata, M. I. M.; Santos, A.C.; Neves, M.; Geraldes, C. F. G. C.; Lima, J. J. P. de

    2002-01-01

    Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp (L1) and the ligand DTPA(BOM)3 (BOM=benzyloxymethyl) (L2), radiolabelled with 153Sm3+ and 111In3+, were studied as potential hepatospecific gamma scintigraphic agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The complexes of L2 show even greater hepatobiliary specificity than L1, perhaps as a consequence of longer blo...

  9. 177 Lu-Dota-octreotate radionuclide therapy of advanced gastrointestinal neuroendocrine tumors: results from a phase II study

    Energy Technology Data Exchange (ETDEWEB)

    Paganelli, Giovanni; Sansovini, Maddalena; Ambrosetti, Alice; Severi, Stefano; Ianniello, Annarita; Matteucci, Federica [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola, FC (Italy); Monti, Manuela; Scarpi, Emanuela [IRST IRCCS, Unit of Biostatistics and Clinical Trials, Meldola (Italy); Donati, Caterina [IRST IRCCS, Oncology Pharmacy Laboratory, Meldola (Italy); Amadori, Dino [IRST IRCCS, Department of Medical Oncology, Meldola (Italy)

    2014-10-15

    We evaluated the activity and safety profile of {sup 177}Lu-Dotatate peptide receptor radionuclide therapy (Lu-PRRT) in patients with advanced, well-differentiated (G1-G2) gastrointestinal neuroendocrine tumors (GI-NETs). Forty-three patients with radiological tumor progression at baseline and a positive Octreoscan registered completed the treatment with Lu-PRRT, resulting in the cumulative activity of 18.5 or 27.8 GBq in five cycles. Total activity was scheduled on the basis of kidney function or bone marrow reserve. Twenty-five (58 %) patients were treated with a ''standard'' Lu-PRRT full dosage (FD) of 25.7 GBq (range 22.2-27.8), while the remaining 18 patients (42 %) who, at enrolment, showed a higher probability of developing kidney or bone marrow toxicity received a reduced dosage (RD) of 18.4 GBq (range 14.4-20.4). According to SWOG criteria, the overall response was complete response (CR) in (7 %) cases and stable disease (SD) in 33 (77 %), with a disease control rate (DCR) of 84 %. Median response duration was 25 months (range 7-50). Median progression-free survival (PFS) was 36 months (95 % CI 24-nr), and median overall survival (OS) has not yet been reached. Remarkably, none of the patients, including those at a higher risk of toxicity, showed side-effects after either dosage of Lu-PRRT. Lu-PRRT was shown to be an effective therapeutic option in our patients with advanced progressive GI-NETs, showing an 84 % DCR (95 % CI 73-95) that lasted for 25 months and a PFS of 36 months. Both activities of 27.8 GBq and 18.5 GBq proved safe and effective in all patients, including those with a higher probability of developing kidney or bone marrow toxicity. (orig.)

  10. Tissue distribution and excretion pattern of 51Cr in animals

    International Nuclear Information System (INIS)

    To study distribution and excretion pattern of chromium, 51CrCl3 was orally administered in doses of 66.6 μCi to each rat. Lungs, liver and testis accumulated relatively higher radioactivity earlier and this accumulation persisted in liver and testis for 192 hr. The lungs, heart muscles and gall bladder showed a gradual decline after initial uptake whereas in kidney and spleen it continued to increase as a function of time. Uptake of 51Cr per unit weight of the small intestine was greater than the stomach and the large intestine. On an average, 70.15 percent of the orally administered 51Cr was excreted in faeces within 192 hr of dosing. In the second experiment, six male kids weighing 23.87 kg, on an average, were given orally 500 μCi of 51Cr. Kids were maintained on concentrate mixture and green berseem which contained 0.43 ppm and 0.195 ppm chromium, respectively. The balance studies revealed that 94.93 percent of the total 51Cr dose was excreted in the faeces and 1.93 percent in the urine during 7 day period. Net absorption of 51Cr was, however, only 9.0 percent. (auth.)

  11. 153Sm-EDTMP治療肺癌多發性骨轉移的臨床應用78例%Clinical applications of 153 Sm-EDTMP in treatment of multiple bone metastases in 78 patients with lung cancer

    Institute of Scientific and Technical Information of China (English)

    肖國有; 李黨生; 梁藝華; 姚新娟

    2001-01-01

    Objective To evaluate the effect of 153Sm-EDTMP in treating patients with lung cancer and multiple bone metastases. Methods A dose of 18.5~25.9MBq/Kg ~Sm-EDTMP was administered once a month to each patient through vein injection according to disease severity and body weight. 3 injections made up one therapy cycle. Results Pain relieves were obtained in 65 patients, with an effective rate of 83.3%. Pain relief of grade Ⅰ was observed in 19 patients (24.3%), grade Ⅱ in 46 patients (59%) and grade Ⅲ in 13 patients (16.7%0),respectively. Lesions of bone metastases disappeared or shrunk in 9 patients, with a positive rate of 11.5 %. which included 3 cases of grade I and 6 cases of grade Ⅱ , respectively. Better effects were obtained in adenocarcinoma and squamous carcinoma than in small cell lung cancer. Conclusion 153Sm-EDTMP is safe and effective in treating patients with lung cancer and multiple bone metastases.

  12. Cytotoxic and genotoxic effects caused by {sup 153} Sm-EDTMP, combined with BrdU a thymidine analog; Efecto citotoxico y genotoxico causado por {sup 153} Sm-EDTMP, combinado con BrdU un analogo de timidina

    Energy Technology Data Exchange (ETDEWEB)

    Morales A, E.; Ferro F, G.; Morales R, P. [ININ, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2006-07-01

    The ablation of the bone marrow previous to the transplant by means of radiation and chemical antineoplastics its affect indiscriminately to the healthy tissues and in particular those that are in proliferation. The objective of this work is to determine the effect of the incorporation from the BrdU to the DNA on the genotoxicity and cytotoxicity of the cells of the bone marrow caused by the radiopharmaceutical {sup 153}Sm-EDTMP. The genotoxicity was determined by the rate of erythrocytes polychromatic micro nucleates (EPC-MN) and the cytotoxicity by the frequency of EPC. Both parameters determined in peripheral blood after the BrdU administration and {sup 153}Sm-EDTMP. The combination of the BrdU and r1 radiopharmaceutical produced a bigger cytotoxicity that the radiation and the BrdU alone; on the other hand it produced a reduction of the EPC-MN produced by the radiation, suggesting that the cytotoxicity didn't allow the expression of the genotoxicity. (Author)

  13. 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

  14. (153)Sm(3+) and (111)In(3+) DTPA derivatives with high hepatic specificity: in vivo and in vitro studies.

    Science.gov (United States)

    Prata, M I M; Santos, A C; Neves, M; Geraldes, C F G C; de Lima, J J P

    2002-07-25

    Two DTPA derivatives, a mono-amide derivative containing an iodinated synthon, DTPA-IOPsp (L(1)) and the ligand DTPA(BOM)(3) (BOM=benzyloxymethyl) (L(2)), radiolabelled with (153)Sm(3+) and (111)In(3+), were studied as potential hepatospecific gamma scintigraphic agents. In vivo studies with Wistar rats show that the main excretory pathway for all the chelates studied is the hepatobiliary system. The complexes of L(2) show even greater hepatobiliary specificity than L(1), perhaps as a consequence of longer blood circulation times due to their strong affinity towards HSA. The (153)Sm(3+) chelates are also more hepatospecific than the corresponding (111)In(3+) chelates. The La(3+) and In(3+) chelates of L(1) and L(2) show some structural and dynamic differences in aqueous solution, as studied by (1)H NMR spectroscopy. While only two nona-coordinated isomers were observed for the La(3+) complexes with both ligands, its number is much larger in the In(3+) complexes, with both octa- and hepta-coordinated species (with unbound side arms), as well as structural isomers for each coordination number. PMID:12121790

  15. Cytotoxic and genotoxic effects caused by 153 Sm-EDTMP, combined with BrdU a thymidine analog

    International Nuclear Information System (INIS)

    The ablation of the bone marrow previous to the transplant by means of radiation and chemical antineoplastics its affect indiscriminately to the healthy tissues and in particular those that are in proliferation. The objective of this work is to determine the effect of the incorporation from the BrdU to the DNA on the genotoxicity and cytotoxicity of the cells of the bone marrow caused by the radiopharmaceutical 153Sm-EDTMP. The genotoxicity was determined by the rate of erythrocytes polychromatic micro nucleates (EPC-MN) and the cytotoxicity by the frequency of EPC. Both parameters determined in peripheral blood after the BrdU administration and 153Sm-EDTMP. The combination of the BrdU and r1 radiopharmaceutical produced a bigger cytotoxicity that the radiation and the BrdU alone; on the other hand it produced a reduction of the EPC-MN produced by the radiation, suggesting that the cytotoxicity didn't allow the expression of the genotoxicity. (Author)

  16. Using the 154 Sm(p,d) reaction to extend the level scheme of 153 Sm to the continuum region

    Science.gov (United States)

    Wilson, Emma; Beausang, Cornelius; Humby, Peter; Simon, Anna; Ross, Timothy; Hughes, Richard; Burke, James; Casperson, Robert; Koglin, Johnathon; Ota, Shuya; Allmond, James; McCleskey, Matthew; McCleskey, Ellen; Saastamoinen, Antti; Chyzh, Roman; Gell, Kristen; Tarlow, Tom; Vyas, Gargi; Starlite Collaboration

    2015-04-01

    Following an experiment performed at the Cyclotron Institute of Texas A&M University, the level scheme of 153 Sm is in the process of being extended. A beam of protons accelerated to 25 MeV impinged on an isotopically enriched 154 Sm target, inducing a (p,d) reaction, thereby producing energetically excited 153 Sm reaction products. The resulting γ-rays and deuterons were detected by the STARLiTe array, which consists of six Compton-suppressed HPGe gamma-ray detectors, and a ΔE-E Si telescope for charged particle identification. In the ongoing analysis of these data, the identification of new γ-rays has been possible. The deuteron spectrum will be used to identify high-lying continuum states, and angular momentum transfer values will be assigned using angular distributions and comparison with DWBA calculations. This work was partly supported by the US DofE under Grant Numbers DE-NA0001801, DE-FG02-05ER41379(UofR); DE-AC52-07NTJKTG(LLNL).

  17. Somatostatin receptor expression in the human spleen - Answer to an enigma by ex-vivo and in-vitro autoradiography after 177Lu-DOTA-octreotate administration

    International Nuclear Information System (INIS)

    Full text of publication follows. Aim: radiolabelled somatostatin analogues are being used for diagnostic and therapeutic (PRRT) purposes in patients with somatostatin receptor (SSTR) expressing tumours. During PRRT a significant spleen uptake may lead to radiation doses of > 20 Gy. Yet, the threshold dose for spleen radiation induced toxicity is currently unknown. Based on previous 68Ga-DOTATOC PET/CT studies, demonstrating higher uptake in spleen than in splenosis, white pulp (WP) localization of radioactivity was suggested. This hypothesis was investigated in the current pilot study using the longer lived 177Lu-DOTA-octreotate. Methods: a patient diagnosed with neuroendocrine neoplasm of the pancreatic tail (SUVmax on 68Ga-DOTATOC PET/CT 100.4) with liver metastasis (SUV 47.3, normal liver SUV 12.5) and uptake in the spleen (SUV 41.0) received 1 GBq 177Lu-DOTA-octreotate. 2 h after administration whole-body planar scintigraphy and SPECT/CT of the upper abdomen was performed, followed by laparoscopic resection of the pancreatic tumour and splenectomy the next day. After spleen transport from Bad Berka to Rotterdam ex-vivo micro-SPECT of the removed spleen was acquired for 73 min using 2.5 mm diameter pinholes. Spleen fragments (∼10 * 10 * 5 mm) were either snap-frozen in liquid nitrogen or fixed in 10% formalin and paraffin embedded. Ex-vivo autoradiography of 10 μm cryo-sections was performed and serial sections were used for 111In-DOTA-octreotate in-vitro autoradiography after decay of 177Lu. FFPE sections were used for HE- and immunostaining for SSTR2A and cell subsets CD4 (Th-cell), CD8 (Ts-cell), CD20 (B-cell) and CD68 (macrophage). Results: 177Lu-DOTA-octreotate scintigraphy and SPECT/CT demonstrated high uptake in the pancreatic tumor, hepatic metastasis and homogeneously in the normal spleen. High resolution micro-SPECT imaging of the isolated spleen also revealed a relatively homogeneous uptake (calculated rest activity 60 MBq 177Lu). The vast

  18. 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

  19. A clinical trial of 153Sm EDTMP in promotion of bone metastatic cancer pains%153钐改善骨转移癌痛疗效观察

    Institute of Scientific and Technical Information of China (English)

    王新

    2002-01-01

    Objective To evaluate the effect of 153Sm EDTMP in the bone metastatic cancer pains.Methods In treatment group(32 patients with bone metastatic diseases) 153Sm EDTMP were given by infusion for one time.In control group,32 patients received radiotherapy. The radio dose was DT30Gy,5 times per week for 2 weeks.Pain relief was used as criteria of response at the time treatment finished and 6 months later.Results At the time treatment finished,there were statistically differences in pain relief between two groups.Pains relief rate was superior to control group after 6 months (P< 0.05).Conclusion Treatment with 153Sm EDTMP one time can reduce apparently pains caused by bone metastases,which is conveniently used and well tolerated.

  20. 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

  1. Improvement in the 1{sup 11}In-DTPA-TYR{sup 3}-octreotide and {sup 177}Lu-DOTATYR{sup 3}- octreotate production

    Energy Technology Data Exchange (ETDEWEB)

    Souza, Adriano A.; Herrerias, Rosana; Pires, Jose A.; Alves, Geraldo P.; Fukumori, Neuza T.O.; Matsuda, Margareth M.N.; Almeida, Erika V.; Mengatti, Jair; Barboza, Marycel F. de, E-mail: aasouza@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2009-07-01

    Recent advances in receptor mediated-tumor imaging have resulted in the development of somatostatin analogues, the biomolecular basis for the clinical use of these compounds in nuclear medicine for diagnostic and peptide receptor radionuclide therapy (PRRT). PRRT is a very good therapeutic option for patients with metastatic neuroendocrine gastroenteropancreatic (GEP) tumour. Clinical studies with different sst-positives tumors proved advantages of [{sup 177}Lu-DOTA-Tyr{sup 3}]octreotate (DOTATATE) for therapy. The aim of this work is to establish and validate the labeling, the quality control procedures of DTPA-Tyr{sup 3}-Octreotide (DTPA-Oct) and DOTA-Tyr{sup 3}-Octreotate (DOTATATE) labeled with In-111 and Lu-177, respectively, for routine production at Radiopharmacy Directory (DIRF) Brazil. Labeling were performed in a 'glove-box' using {sup 111}InCl{sub 3} (Nordion) and in hot-cell with {sup 177}LuCl{sub 3} (IDB-Holland) at pH 4.5; using DTPA-Oct (Pichem) and DOTATATE (IDBHolland) at room temperature and at 82-85 deg C for 30 minutes, respectively. The radiochemical purity was determined by ITLC-SG in 0.1 mol L{sup -1} sodium citrate, pH 5.5 and by Sep-Pak silica cartridge. Sterility was performed by the microbiology procedures and pyrogen tests by the 'in-vitro' Limulus test (LAL). The stability of both radiolabeled peptides was high even 72 hours under refrigeration. The radiochemical purities of the labeled compounds were confirmed by HPLC. Sterility and pyrogen tests were negative in all delivered vials. The efficient procedure to obtain {sup 111}In-DTPA-Oct and {sup 177}Lu-DOTATATE was confirmed in the first comparative clinical groups. The methods were validated and 46.287 GMBq of {sup 111}In-DTPA-Oct and 1,193 GBq of {sup 177}Lu-DOTATATE were distributed in 2008, to nuclear medicine services in Brazil. (author)

  2. 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.

  3. Formation of medical radioisotopes {sup 111}In, {sup 117m}Sn, {sup 124}Sb, and {sup 177}Lu in photonuclear reactions

    Energy Technology Data Exchange (ETDEWEB)

    Danagulyan, A. S.; Hovhannisyan, G. H., E-mail: hov-gohar@ysu.am; Bakhshiyan, T. M. [Yerevan State University (Armenia); Avagyan, R. H.; Avetisyan, A. E.; Kerobyan, I. A.; Dallakyan, R. K. [A.I. Alikhanian National Science Laboratory (Yerevan Physics Institute) (YerPhI) (Armenia)

    2015-06-15

    The possibility of the photonuclear production of radioisotopes {sup 111}In, {sup 117m}Sn, {sup 124}Sb, and {sup 177}Lu is discussed. Reaction yields were measured by the gamma-activation method. The enriched tin isotopes {sup 112,} {sup 118}Sn and Te and HfO{sub 2} of natural isotopic composition were used as targets. The targets were irradiated at the linear electron accelerator of Alikhanian National Science Laboratory (Yerevan) at the energy of 40 MeV. The experimental results obtained in this way reveal that the yield and purity of radioisotopes {sup 111}In and {sup 117}mSn are acceptable for their production via photonuclear reactions. Reactions proceeding on targets from Te and HfO{sub 2} of natural isotopic composition and leading to the formation of {sup 124}Sb and {sup 177}Lu have small yields and are hardly appropriate for the photoproduction of these radioisotopes even in the case of enriched targets.

  4. Preclinical evaluation of a diabody-based (177)Lu-radioimmunoconjugate for CD22-directed radioimmunotherapy in a non-Hodgkin lymphoma mouse model.

    Science.gov (United States)

    Weber, Tobias; Bötticher, Benedikt; Arndt, Michaela A E; Mier, Walter; Sauter, Max; Exner, Evelyn; Keller, Armin; Krämer, Susanne; Leotta, Karin; Wischnjow, Artjom; Grosse-Hovest, Ludger; Strumberg, Dirk; Jäger, Dirk; Gröne, Hermann-Josef; Haberkorn, Uwe; Brem, Gottfried; Krauss, Jürgen

    2016-10-28

    Radioimmunotherapy is considered as treatment option in recurrent and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). To overcome the dose limiting bone marrow toxicity of IgG-based radioimmunoconjugates (RICs), we modified a humanized diabody with 5-, 10-, or 20-kDa polyethylene glycol (PEG) for CD22-targeted radioimmunotherapy using the low-energy β-emitter lutetium-177 ((177)Lu). A favorable pharmacokinetic profile was observed for the 10-kDa-PEG-diabody in nude mice being xenografted with subcutaneous human Burkitt lymphoma. Even at high doses of 16 MBq this diabody RIC was well tolerated by NOD Rag1(null) IL2rγ(null) (NRG) mice and did not reveal signs of organ long-term toxicity 80 days post injection. Combination therapy of the diabody RIC with unconjugated anti-CD20 Rituximab demonstrated therapeutic efficacy in established disseminated mantle cell lymphoma xenograft models. When compared with the combination of the IgG formatted (177)Lu anti-CD22 antibody and Rituximab, dual targeted therapy with the diabody RIC achieved an improved reduction of disease burden in the first nine days following treatment. The data indicate that the PEGylated anti-CD22 diabody may have potential for extending the repertoire of radiopharmaceuticals for the treatment of patients with B-NHL. PMID:27524505

  5. 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.

  6. The features of kinetics of 153Sm-oksabifor in bone metastases of cancer of different localization

    International Nuclear Information System (INIS)

    Provide evaluation of investigation of kinetics of 153Sm-oksabifor in metastases of cancer the results of complex scintigraphic investigations of 26 patients who were treated by radionuclide therapy were analyzed. The angioscintigraphy during 60 seconds, dynamic scintigraphy during 60-90 minutes and whole body scanning after intravenous bolus injection of 4130-4950 MBq of the radiopharmaceutical in sequence were made. Considerable variability of indices of the radiopharmaceutical kinetics was determined. The features of angioscintigrams from bone metastases with intensive accumulation of the radiopharmaceutical are a short descending segment or its absents and passing an ascending segment into plateau or slowly ascending curve, which are determined the radiopharmaceutical fixation in metastases during first passing the bolus through the vessels. Character of the radiopharmaceutical fixation at angioscintigraphy may be a prognostic factor of the efficacy of radionuclide therapy

  7. Exposure of personnel and public due to using 153Sm-labelled EDTMP-QuadrametR in nuclear medicine procedures

    International Nuclear Information System (INIS)

    The main aim of this study was to highlight the problems of personnel exposure when administering 153Sm-labelled ethylene diamine tetramethylene phosphonate-QuadrametR to patients and especially to evaluate hand exposure of the personnel. The exposure levels of patients' families and the people who takes care of the patients treated by QuadrametR were also estimated. Thermoluminescent detectors were used to measure the doses. The doses received during the injection of the QuadrametR by the nursing staff have been determined at the level of 1/150 dose limit for the skin. Exposure of members of the patient's family staying 1.5 m away from the patient being treated with QuadrametR has been estimated to be 0.40 mGy. (authors)

  8. 99TC-MDP@153Sm-EDTMP治疗骨转移癌64例报告

    Institute of Scientific and Technical Information of China (English)

    张萌萌; 常淑玲; 王淑芬; 张宗英; 郭忠

    2001-01-01

    @@恶性肿瘤骨转移(也称骨转移癌)导致的剧烈、持续性骨痛,给患者带来难以忍受的痛苦,放疗、化疗对骨转移癌的治疗已经临床证实疗效不明显.笔者应用99TC-MDP(99锝-亚甲基二磷酸盐)、153Sm-EDTMP(153钐-乙二胺四亚甲基磷酸)治疗收到较好疗效.现报道如下. 1资料与方法 1.1病例资料(1)治疗对象:经临床检查、SPECT全身显像诊断的54例恶性肿瘤骨转移患者中,肺癌18例,乳腺癌10例,直肠癌7例,肝癌3例,鼻咽癌2例,其他恶性肿瘤14例.本组执行“完整疗程”;(2)治疗对照组:经临床检查、SPECT全身显像诊断的10例恶性肿瘤骨转移患者中肺癌7例,乳腺癌2例,直肠癌1例. 1.2治疗药物99TC-MDP为中国核动力研究设计院成都同位素研究所提供,153Sm-EDTMP为中国原子能研究院,北京同位素应用研究所提供.

  9. 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)

  10. Survival curves study of platelet labelling with 51Cr

    International Nuclear Information System (INIS)

    Platelet kinetics and idiopathic thrombocytopenic purpura were researched in the literature. An 'in vitro' platelet labelling with 51Cr procedure in implementation has been evaluated in human beings. Functions used for fitting considered the cases whether the curve was linear or exponential as well as the presence of hematies. (author)

  11. Production and first use of {sup 153}SmCl{sub 3}-ion exchange resin capsule formulation for assessing gastrointestinal motility

    Energy Technology Data Exchange (ETDEWEB)

    Yeong, Chai-Hong; Abdullah, Basri Johan Jeet; Ng, Kwan-Hoong [University of Malaya Research Imaging Centre, University of Malaya, 50603 Kuala Lumpur (Malaysia); Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Chung, Lip-Yong [Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Goh, Khean-Lee [Department of Medicine, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Sarji, Sazilah Ahmad [University of Malaya Research Imaging Centre, University of Malaya, 50603 Kuala Lumpur (Malaysia); Department of Biomedical Imaging, Faculty of Medicine, University of Malaya, 50603 Kuala Lumpur (Malaysia); Perkins, Alan Christopher, E-mail: alan.perkins@nottingham.ac.uk [Radiological and Imaging Sciences and Nottingham Digestive Diseases Biomedical Research Unit, University of Nottingham, Nottingham NG7 2UH (United Kingdom)

    2012-03-15

    We produced an enteric-coated gelatine capsule containing neutron-activated {sup 153}Sm-labelled resin beads for use in gastrointestinal motility studies. In vitro test in simulated gastrointestinal environment and in vivo study on volunteers were performed. Scintigraphic images were acquired from ten volunteers over 24 h while blood and urine samples were collected to monitor the presence of {sup 153}Sm. All the capsules remained intact in stomach. This proved to be a safe and practical oral capsule formulation for whole gut transit scintigraphy. - Highlights: Black-Right-Pointing-Pointer Enteric-coated gelatin capsule containing {sup 153}Sm-labelled resin was manufactured. Black-Right-Pointing-Pointer In vitro disintegration test ensured targeted release properties of the formulation. Black-Right-Pointing-Pointer In vivo volunteers study confirmed safeness and practical use of the formulation. Black-Right-Pointing-Pointer {sup 153}Sm can be used as an alternative nuclide to {sup 111}In in GI transit scintigraphy.

  12. Polyphosphoric acid capping radioactive/upconverting NaLuF4:Yb,Tm,153Sm nanoparticles for blood pool imaging in vivo.

    Science.gov (United States)

    Peng, Juanjuan; Sun, Yun; Zhao, Lingzhi; Wu, Yongquan; Feng, Wei; Gao, Yanhong; Li, Fuyou

    2013-12-01

    Nanoparticles that circulate in the bloodstream for a prolonged period of time have important biomedicine applications. However, no example of lanthanide-based nanoparticles having a long-term circulation bloodstream has been reported to date. Herein, we report on difunctional radioactive and upconversion nanoparticles (UCNP) coated with polyphosphoric acid ligand, that is ethylenediamine tetramethylenephosphonic acid (EDTMP), for an application in single-photon emission computed tomography (SPECT) blood pool imaging. The structure, size and zeta-potential of the EDTMP-coated nanoparticles (EDTMP-UCNP) are verified using transmission electron microscopy and dynamic light scattering. Injection of radioisotope samarium-153-labeled EDTMP-UCNP (EDTMP-UCNP:(153)Sm) into mice reveal superior circulation time compared to control nanoparticles coated with citric acid (cit-UCNP:(153)Sm) and (153)Sm complex of EDTMP (EDTMP-(153)Sm). The mechanism for the extended circulation time may be attributed to the adhesion of EDTMP-UCNP on the membrane of red blood cells (RBCs). In vivo toxicity results show no toxicity of EDTMP-UCNP at the dose of 100 mg/kg, validating its safety as an agent for blood pool imaging. Our results provide a new strategy of nanoprobe for a long-term circulation bloodstream by introducing polyphosphoric acid as surface ligand.

  13. Comparison of sequential planar {sup 177}Lu-DOTA-TATE dosimetry scans with {sup 68}Ga-DOTA-TATE PET/CT images in patients with metastasized neuroendocrine tumours undergoing peptide receptor radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sainz-Esteban, Aurora; Carril, Jose Manuel [Hospital Universitario Marques de Valdecilla, Department of Nuclear Medicine, Santander (Spain); Prasad, Vikas; Schuchardt, Christiane; Zachert, Carolin; Baum, Richard P. [Zentralklinik Bad Berka, Department of Nuclear Medicine and Centre for PET/CT, Bad Berka (Germany)

    2012-03-15

    The aim of the study was to compare sequential {sup 177}Lu-DOTA-TATE planar scans ({sup 177}Lu-DOTA-TATE) in patients with metastasized neuroendocrine tumours (NET) acquired during peptide receptor radionuclide therapy (PRRT) for dosimetry purposes with the pre-therapeutic {sup 68}Ga-DOTA-TATE positron emission tomography (PET)/CT ({sup 68}Ga-DOTA-TATE) maximum intensity projection (MIP) images obtained in the same patients concerning the sensitivity of the different methods. A total of 44 patients (59 {+-} 11 years old) with biopsy-proven NET underwent {sup 68}Ga-DOTA-TATE and {sup 177}Lu-DOTA-TATE imaging within 7.9 {+-} 7.5 days between the two examinations. {sup 177}Lu-DOTA-TATE planar images were acquired at 0.5, 2, 24, 48 and 72 h post-injection; lesions were given a score from 0 to 4 depending on the uptake of the radiopharmaceutical (0 being lowest and 4 highest). The number of tumour lesions which were identified on {sup 177}Lu-DOTA-TATE scans (in relation to the acquisition time after injection of the therapeutic dose as well as with regard to the body region) was compared to those detected on {sup 68}Ga-DOTA-TATE studies obtained before PRRT. A total of 318 lesions were detected; 280 (88%) lesions were concordant. Among the discordant lesions, 29 were {sup 68}Ga-DOTA-TATE positive and {sup 177}Lu-DOTA-TATE negative, whereas 9 were {sup 68}Ga-DOTA-TATE negative and {sup 177}Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for {sup 177}Lu-DOTA-TATE as compared to {sup 68}Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) {sup 177}Lu-DOTA-TATE images (91%) as compared to the immediate (30 min) images (68%). The highest concordance was observed for bone metastases (97%) and the lowest for head/neck lesions (75%). Concordant lesions (n = 77; mean size 3.8 cm) were significantly larger than discordant lesions (n = 38; mean size 1.6 cm) (p < 0.05). No such significance was

  14. Investigating the Effect of Ligand Amount and Injected Therapeutic Activity: A Simulation Study for 177Lu-Labeled PSMA-Targeting Peptides

    Science.gov (United States)

    Schuchardt, Christiane; Kulkarni, Harshad R.; Shahinfar, Mostafa; Singh, Aviral; Glatting, Gerhard; Baum, Richard P.; Beer, Ambros J.

    2016-01-01

    In molecular radiotherapy with 177Lu-labeled prostate specific membrane antigen (PSMA) peptides, kidney and/or salivary glands doses limit the activity which can be administered. The aim of this work was to investigate the effect of the ligand amount and injected activity on the tumor-to-normal tissue biologically effective dose (BED) ratio for 177Lu-labeled PSMA peptides. For this retrospective study, a recently developed physiologically based pharmacokinetic model was adapted for PSMA targeting peptides. General physiological parameters were taken from the literature. Individual parameters were fitted to planar gamma camera measurements (177Lu-PSMA I&T) of five patients with metastasizing prostate cancer. Based on the estimated parameters, the pharmacokinetics of tumor, salivary glands, kidneys, total body and red marrow was simulated and time-integrated activity coefficients were calculated for different peptide amounts. Based on these simulations, the absorbed doses and BEDs for normal tissue and tumor were calculated for all activities leading to a maximal tolerable kidney BED of 10 Gy2.5/cycle, a maximal salivary gland absorbed dose of 7.5 Gy/cycle and a maximal red marrow BED of 0.25 Gy15/cycle. The fits yielded coefficients of determination > 0.85, acceptable relative standard errors and low parameter correlations. All estimated parameters were in a physiologically reasonable range. The amounts (for 25−29 nmol) and pertaining activities leading to a maximal tumor dose, considering the defined maximal tolerable doses to organs of risk, were calculated to be 272±253 nmol (452±420 μg) and 7.3±5.1 GBq. Using the actually injected amount (235±155 μg) and the same maximal tolerable doses, the potential improvement for the tumor BED was 1–3 fold. The results suggest that currently given amounts for therapy are in the appropriate order of magnitude for many lesions. However, for lesions with high binding site density or lower perfusion, optimizing the

  15. Genotoxic evaluation of [DOTA,Tyr3]octreotate labeled with 131I and 177Lu in human peripheral lymphocytes in vitro by micronucleus assay

    International Nuclear Information System (INIS)

    The radiolabeled receptor-binding peptides have being used for cancer diagnosis and therapy. The octreotate, a somatostatin analogue peptide, bound to various tumors expressing sst receptors (thyroid, pancreas, prostrate, melanoma and lymphomas). The amount and the type of receptors for somatostatin influence the tissue uptake. The [DOTA, Tyr3]octreotate has been used because of its high affinity to somatostatin subtype receptors sstr2 and sstr5. The pharmacokinetic study showed that the blood clearance is rapid and only 9% of the intravenous injected activity remains in human blood after one hour. The aim of this study was to evaluate the cytogenetic effect of radiolabeled [DOTA, Tyr3]octreotate in blood cells in vitro, using the cytokinesis-block micronucleus (MN) assay. This technique allows evaluating the mutagenic effects of both endogenous and exogenous agents at chromosome level. Blood samples of healthy donors were collected in heparinized syringes and exposed to different activities of [DOTA, Tyr3]octreotate labeled with with 131I (n=3) and 177Lu (n=3), where radioactive concentration ranged from 600 to 5600 kBq/mL, corresponding to an injected activity of 3.1 to 28.9 GBq in a reference man of 70 kg weight. 131I and 177Lu are beta- and gamma-emitters. After one-hour exposition to radiopharmaceuticals at 37 deg C, the cells were washed with culture medium for removing the non internalised octreotate and cultivated for 72 hours, according to criteria adopted by the IAEA. The results showed a positive correlation between radioactive concentrations (X) and the frequency of binucleated cells with micronuclei (Y) (P131I-DOTA, Tyr3]octreotate was Y = (1.634 ± 0.236) + (0.912 ± 0.137) 10-3 X and for [177Lu-DOTA, Tyr3]octreotate was Y = (1.715 ± 0.342) + (0.743 ± 0.135) 10-3 X. The non labeled molecule, [DOTA, Tyr3]octreotate, has no influence in the induction of cytogenetic damage. The micronucleus assay with rat pancreatic tumor cells (AR42J) that express the

  16. 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.

  17. Urine management after treatment with ''153 Sm-EDTMP (QUADRAMET); Gestion de la orina en el tratamiento con ''153 Sm-EDTMP (QUADRAMET)

    Energy Technology Data Exchange (ETDEWEB)

    Delgado, A.; Diaz, J. P.; Carrasco, J. L.; Jimenez-Hoyuela, J. M.; Rebollo, A. C.; Martinez del Valle, M. D.; Ortega, S. J.

    2004-07-01

    The main purpose was to establish and to evaluate a new protocol of individualized treatment of patient urine after ''153 Sm-EDTMP injection, with a more efficient management of the wastes. Excreted urine was collected in an appropriate container form which, previous to sealing it, an aliquot of 10 ml was obtained. Experimental half-life (t1/2) of the isotope was then determined by measuring the activity at different times, besides the minimum time necessary for disposing of the radioactive wastes as regular trash. The measured half-life adjusted well to the theoretical value of the isotope. The time of considered storage oscillated between 19 and 26 days, based on the activity excreted by each patient. The main idea is the consideration of the set container-urine as solid waste: the evaluation of the minimum storage time necessary to its elimination is made in terms of legal limitation of specific activity by mass unit. The immediate advantages ares: the elimination of disagreeable scents by the storage of urine, it is not necessary a liquid waste disposal to eliminate it, and a more accurate knowledge of the specific activity at the moment of the elimination (dilution factor is not used). (Author) 10 refs.

  18. 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.)

  19. Enhancement of somatostatin-receptor-targeted 177Lu-[DOTAdeg. C, -Tyr3]-octreotide therapy by gemcitabine pretreatment-mediated receptor uptake, up-regulation and cell cycle modulation

    International Nuclear Information System (INIS)

    Introduction: Clinical studies of patients treated with somatostatin-receptor (sstr)-targeted [DOTAdeg. C, -Tyr3]-octreotide (DOTATOC) labeled with 177Lu and 9deg. C, Y have shown overall response rates in the range of 9-33%. This study evaluates the potential for combination therapy with gemcitabine in an effort to improve clinical outcomes. Methods: Human pancreatic adenocarcinoma Capan-2, rat pancreatic cancer AR42J and human small cell lung cancer NCI-H69 cells were each treated with 1 μg/ml gemcitabine for 4 days followed by replacement of the medium alone for four additional days. Cell cycle and direct receptor-uptake studies were performed with 177Lu-DOTATOC after the total 8-day treatment as described. Cell viability and apoptosis experiments were performed to study the effects of gemcitabine pretreatment and 177Lu-DOTATOC radionuclide therapy. Parallel control studies were performed with receptor-non-targeted 177Lu-DOTA and DOTATOC. Results: Cells treated with gemcitabine for 4 days showed a down-regulation of sstr expression as determined by 177Lu-DOTATOC uptake. However, after 4 days of additional growth in absence of gemcitabine, the uptake of 177Lu-DOTATOC was 1.5-3 times greater than that of the untreated control cells. In gemcitabine-pretreated Capan-2 cells, 84% of the cell population was in the G2M phase of the cell cycle. Due to sstr up-regulation and cell cycle modulations, synergistic effects of gemcitabine pretreatment were observed in cell viability and apoptosis assays. 177Lu-DOTATOC resulted in two to three times greater apoptosis in gemcitabine-pretreated Capan-2 cells compared to the untreated cells. Conclusion: Gemcitabine pretreatment up-regulates sstr expression and acts as a radiosensitizer through cell cycle modulation. The rational combination of gemcitabine and sstr-targeted radiopharmaceuticals represents a promising chemoradiation therapeutic tool with great potential to improve clinical outcomes and, thus, merits further study

  20. Enhancement of somatostatin-receptor-targeted {sup 177}Lu-[DOTAdeg. C, -Tyr{sup 3}]-octreotide therapy by gemcitabine pretreatment-mediated receptor uptake, up-regulation and cell cycle modulation

    Energy Technology Data Exchange (ETDEWEB)

    Nayak, Tapan K. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, NM 87131 (United States); Atcher, Robert W. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Bioscience Division, Los Alamos National Laboratory, Los Alamos, NM 87545 (United States); Prossnitz, Eric R. [Department of Cell Biology and Physiology, School of Medicine, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States); Norenberg, Jeffrey P. [College of Pharmacy, University of New Mexico, Albuquerque, NM 87131 (United States); Cancer Research and Treatment Center, University of New Mexico, Albuquerque, NM 87131 (United States)], E-mail: jpnoren@unm.edu

    2008-08-15

    Introduction: Clinical studies of patients treated with somatostatin-receptor (sstr)-targeted [DOTAdeg. C, -Tyr{sup 3}]-octreotide (DOTATOC) labeled with {sup 177}Lu and {sup 9}deg. C, Y have shown overall response rates in the range of 9-33%. This study evaluates the potential for combination therapy with gemcitabine in an effort to improve clinical outcomes. Methods: Human pancreatic adenocarcinoma Capan-2, rat pancreatic cancer AR42J and human small cell lung cancer NCI-H69 cells were each treated with 1 {mu}g/ml gemcitabine for 4 days followed by replacement of the medium alone for four additional days. Cell cycle and direct receptor-uptake studies were performed with {sup 177}Lu-DOTATOC after the total 8-day treatment as described. Cell viability and apoptosis experiments were performed to study the effects of gemcitabine pretreatment and {sup 177}Lu-DOTATOC radionuclide therapy. Parallel control studies were performed with receptor-non-targeted {sup 177}Lu-DOTA and DOTATOC. Results: Cells treated with gemcitabine for 4 days showed a down-regulation of sstr expression as determined by {sup 177}Lu-DOTATOC uptake. However, after 4 days of additional growth in absence of gemcitabine, the uptake of {sup 177}Lu-DOTATOC was 1.5-3 times greater than that of the untreated control cells. In gemcitabine-pretreated Capan-2 cells, 84% of the cell population was in the G{sub 2}M phase of the cell cycle. Due to sstr up-regulation and cell cycle modulations, synergistic effects of gemcitabine pretreatment were observed in cell viability and apoptosis assays. {sup 177}Lu-DOTATOC resulted in two to three times greater apoptosis in gemcitabine-pretreated Capan-2 cells compared to the untreated cells. Conclusion: Gemcitabine pretreatment up-regulates sstr expression and acts as a radiosensitizer through cell cycle modulation. The rational combination of gemcitabine and sstr-targeted radiopharmaceuticals represents a promising chemoradiation therapeutic tool with great potential

  1. Preparation and quality control of 177Lu-DOTA-Rituximab for radioimmunotherapy of relapsed and refractory B-cell NHL patients

    International Nuclear Information System (INIS)

    Full text of publication follows. Background: the prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumor-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumor cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immuno-conjugate of Rituximab and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Methods: Rituximab was desalted with sodium bi-carbonate (0.1 M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in-vitro stability and pyrogenicity were studied. Immunoreactivity of 177Lu-DOTA-Rituximab was assessed using RAMOS cells. The radio-immuno-conjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. Results: an average of 4.02 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single Rituximab antibody. The radiochemical purity of the labelled antibody was >95 % with preserved affinity for CD20 antigen. The final preparation was stable up to ∼120 hours when tested under different conditions. Bacterial endotoxin level in the sample was less than the permissible levels(<0.2 EU/ml). A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. Conclusion: a favorable radiochemical purity, stability and biodistribution of the radiolabelled immuno-conjugate indicated that 177Lu-DOTA-antiCD20 antibody-Rituximab might be a promising therapeutic agent for the treatment of relapsed and refractory Non Hodgkin's Lymphoma. (authors)

  2. Radiochemical investigations of 177Lu-DOTA-8-Aoc-BBN[7-14]NH2: an in vitro/in vivo assessment of the targeting ability of this new radiopharmaceutical for PC-3 human prostate cancer cells

    International Nuclear Information System (INIS)

    Bombesin (BBN), a 14 amino acid peptide, is an analogue of human gastrin releasing peptide (GRP) that binds to GRP receptors (GRPr) with high affinity and specificity. The GRPr is over expressed on a variety of human cancer cells including prostate, breast, lung, and pancreatic cancers. The specific aim of this study was to identify a BBN analogue that can be radiolabeled with 177Lu and maintains high specificity for GRPr positive prostate cancer tumors in vivo. A preselected synthetic sequence via solid phase peptide synthesis (SPPS) was designed to produce a DOTA-BBN (DOTA 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) conjugate with the following general structure: DOTA-X-Q-W-A-V-G-H-L-M-(NH2), where the spacer group, X = ω-NH2(CH2)7COOH (8-Aoc). The BBN-construct was purified by reversed phase-HPLC (RP-HPLC). Electrospray Mass Spectrometry (ES-MS) was used to characterize both metallated and non-metallated BBN-conjugates. The new DOTA-conjugate was metallated with 177Lu(III)Cl3 or non-radioactive Lu(III)Cl3. The 177Lu(III)- and non-radiolabeled Lu(III)-conjugates exhibit the same retention times under identical RP-HPLC conditions. The 177Lu-DOTA-8-Aoc-BBN[7-14]NH2 conjugate was found to exhibit optimal pharmacokinetic properties in CF-1 normal mice. In vitro and in vivo models demonstrated the ability of the 177Lu-DOTA-8-Aoc-BBN[7-14]NH2 conjugate to specifically target GRP receptors expressed on PC-3 human prostate cancer cells

  3. Radiolabelled {sup 153}Sm-chelates of glycoconjugates: multivalence and topology effects on the targeting of the asialoglycoprotein receptor

    Energy Technology Data Exchange (ETDEWEB)

    Torres, S. [Centro de Quimica, Campus de Gualtar, Univ. do Minho, Braga (Portugal); Martins, J.A.; Andre, J.P.; Neves, M. [Inst. Tecnologico e Nuclear, Sacavem (Portugal); Santos, A.C.; Prata, M.I.M. [Servico de Biofisica, IBILI, Univ. de Coimbra (Portugal); Geraldes, C.F.G.C. [Dept. de Bioquimica, Centro de Espectroscopia RMN e Centro de Neurociencias e Biologia Celular, Univ. de Coimbra (Portugal)

    2007-07-01

    In this paper we report and discuss the biodistribution studies with Wistar rats of a series of {sup 153}Sm(III)-glycoconjugates, based on DO3A and DO2A(cis) scaffolds (DO3A = 1,4,7-tris(carboxymethyl)-1,4,7,10-tetraazacyclododecane; DO2A(cis) = 1,4-bis(carboxymethyl)-1,4,7,10-tetraazacyclododecane). The effects of changing the sugar type (galactose, lactose and glucose), valency (mono and divalent) and topology on the targeting ability of the liver asialoglycoprotein receptor (ASGPR) are evaluated. Divalent glycoconjugates with different topologies were generated by a pendant glycodendrimeric (generation 1) architecture on a DO3A scaffold and by a linear DO2A(cis)-bis derivative. The results show that the galactose conjugates are more target efficient than the lactose analogues, while the glucose conjugates have no liver targeting ability. Divalent galactose conjugates are more efficiently targeted to the liver than the monovalent ones, while the dendrimeric topology of DO3A-Gal{sub 2} has higher targeting efficiency than that of the DO2A(cis)-Gal{sub 2}. (orig.)

  4. Dosimetric study of radium-223 chloride and 153Sm-EDTMP for treatment of bone metastases using MCNPX code and available experimental data

    International Nuclear Information System (INIS)

    Radium-223 chloride is an alpha emitter radiopharmaceutical which recently has been used for treatment of bone metastases. Absorbed and equivalent doses of 223RaCl2 were studied using MCNPX Monte Carlo code in a phantom consisted of bone marrow, bone and soft tissue. 153Sm-EDTMP as a beta emitter was also simulated for comparison with 223RaCl2. Results show that by injection of 100 µCi 223RaCl2 against 70 mCi 153Sm-EDTMP to a 70 kg adult man, equivalent dose of metastatic bone can be increased about six times without significant increase in delivered dose to healthy tissues. These results demonstrated acceptable agreement with experimental data. (author)

  5. Evaluation of the dinical curative effect of using 153Sm-EDTMP in painful bone metastasis of malignant tumor%153Sm-乙二胺四甲基撑膦酸治疗恶性肿瘤骨转移疼痛

    Institute of Scientific and Technical Information of China (English)

    张晓娟; 晋建华; 刘建中; 李思进; 李险峰; 张承刚; 郭睿; 宁艳丽

    2008-01-01

    目的 评价153Sm-乙二胺四甲基撑膦酸(153Sm-EDTMP)在恶性肿瘤骨转移疼痛治疗中的临床应用价值.方法 对80例骨转移癌患者进行153Sm-EDTMP治疗,按22.2~37 MBq/kg体重一次性静脉注射给药.按照视觉模拟评分法和Kamofsky评分标准,分别评价治疗前后患者疼痛缓解及生活质量改善情况.结果 153Sm-EDTMP治疗的80例骨转移癌患者中,疼痛缓解总有效率为68.75%.其中前列腺癌骨转移癌痛缓解率最高,达81.82%,其次为乳腺癌和肺癌,分别为80.00%、75.00%.分析治疗前后Karnofsky评分变化情况,发现疼痛级别越高生活质量改善越明显.结论 153Sm-EDTMP对恶性肿瘤骨转移所致的疼痛具有较好的缓解作用,对中、重度骨痛患者的生活质量有明显的改善,该法是使用放疗、镇痛药物等方法治疗骨转移癌痛的有益补充.%Objective To evaluate the clinical curative effect of using 153Sm-EDTMP in painful bone metastasis of malignant tumor. Methods Eighty patients with bone metastasis of malignant rumor underwent radionuclide bone palliation therapy were analysed.The treatment efficacy was evaluated by visual analogue scale (VAS) and Kamofsky performance scale.Results 68.75% of patients had a positive response.A better analgesic effect was found in cases of lung,prostate and breast carcinoma metastasm compared to metastasis from other malignant lesions.Improvement of performance in Karnofsky scale was found in cases of midrange and heavy range patients.Conclusion The analgesic effects of 153Sm-EDTMP is obvious in painful bone metastasis of malignant tumor.Improvement of life quality is significant in cases of midrange and heavy range patients.The therapeusis is a beneficial supplement of radiotherapy and odynolysis therapy.

  6. 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

  7. 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

  8. 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

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

    International Nuclear Information System (INIS)

    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 (177Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH2) 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.

  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. 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.)

  12. 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.)

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

    International Nuclear Information System (INIS)

    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 177Lu-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.)

  14. Calculation of the Dose of Samarium-153-Ethylene Diamine Tetramethylene Phosphonate (153Sm-EDTMP as a Radiopharmaceutical for Pain Relief of bone Metastasis

    Directory of Open Access Journals (Sweden)

    Fatemeh Razghandi

    2016-04-01

    Full Text Available Introduction One of the important applications of nuclear physics in medicine is the use of radioactive elements as radiopharmaceuticals. Metastatic bone disease is the most common form of malignant bone tumors. Samarium-153-ethylene diamine tetramethylene phosphonate (153Sm-EDTMP as a radiopharmaceutical is used for pain palliation. This radiopharmaceutical usually emits beta particles, which have a high uptake in bone tissues. The purpose of this study was to calculate the radiation dose distribution of 153Sm-EDTMP in bone and other tissues, using MCNPX Monte Carlo code in the particle transport model. Materials and Methods Dose delivery to the bone was simulated by seeking radiopharmaceuticals on the bone surface. The phantom model had a simple cylindrical geometry and included bone, bone marrow, and soft tissue. Results The simulation results showed that a significant amount of radiation dose was delivered to the bone by the use of this radiopharmaceutical. Conclusion Thebone acted as a fine protective shield against rays for the bone marrow. Therefore, the trivial absorbed dose by the bone marrow caused less damage to bone-making cells. Also, the high absorbed dose of the bone could destroy cancer cells and relieve the pain in the bone.

  15. Variations in absorbed doses from 51Cr in investigations with labelled erythrocytes

    International Nuclear Information System (INIS)

    In nuclear medicine 51Cr labelled red blood cells are used to determine erythrocyte volume, red cell survival, or the site of red cell destruction. The author examined the variations in adsorbed doses from 51Cr in 77 patients with various diseases in whom erythrokinetic investigations were performed for diagnostic purposes. Autologous erythrocytes were incubated with Na2CrO4 (37 kBq (1.0 uCi) 51Cr/kg body weight) and injected intravenously. 51Cr activity in blood was then followed for 10 weeks. 51Cr activity over liver, spleen, and sacrum and whole-body retention of 51Cr were measured for the same period. A compartmental model was assumed to describe the kinetics of 51Cr tagged to red blood cells. It is a noncirculating linear model with the compartments represented by organs (spleen, liver, bone, residual body) rather than physiological compartments. The computer program SAAM-25 was used to provide the kinetic parameters and the organ retention functions. From the cumulated activities of the source regions, organ doses and effective dose equivalents were calculated according to the MIRD concepts. The highest organ doses were found for spleen, liver, and red marrow. The calculated dose values for 51Cr found in this study confirm only partly the values reported in ICRP Publication 17, but are higher up to a factor of 9 for some organs. 16 references, 1 figure, 3 tables

  16. 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

  17. Clinical results of radionuclide therapy of neuroendocrine tumours with {sup 90}Y-DOTATATE and tandem {sup 90}Y/{sup 177}Lu-DOTATATE: which is a better therapy option?

    Energy Technology Data Exchange (ETDEWEB)

    Kunikowska, Jolanta; Krolicki, Leszek [Medical University of Warsaw, Nuclear Medicine Department, Warsaw (Poland); Hubalewska-Dydejczyk, Alicja; Sowa-Staszczak, Anna [Collegium Medicum Cracow, Cracow (Poland); Mikolajczak, Renata; Pawlak, Dariusz [Institute of Atomic Energy POLATOM, Swierk-Otwock (Poland)

    2011-10-15

    Peptide receptor radionuclide therapy (PRRT) using radiolabelled somatostatin analogues is a treatment option for patients with disseminated neuroendocrine tumours (NET). A combination treatment using the high-energy {sup 90}Y beta emitter for larger lesions and the lower energy {sup 177}Lu for smaller lesions has been postulated in the literature.The aim of the study was to evaluate combined {sup 90}Y/{sup 177}Lu-DOTATATE therapy in comparison to {sup 90}Y-DOTATATE alone. Fifty patients with disseminated NET were included in the study prospectively and divided into two groups: group A (n = 25) was treated with {sup 90}Y-DOTATATE, whereas group B (n = 25) received the 1:1 {sup 90}Y/{sup 177}Lu-DOTATATE. The administered activity was based on 3.7 GBq/m{sup 2} body surface area in three to five cycles, with amino acid infusion for nephroprotection. The median overall survival time in group A was 26.2 months while in group B median survival was not reached. Overall survival was significantly higher in group B (p = 0.027). Median event-free survival time in group A was 21.4 months and in group B 29.4 months (p > 0.1). At the 12-month follow-up, comparison of group A vs group B showed stable disease (SD) in 13 vs 16 patients, disease regression (RD) in 5 vs 3 patients and disease progression (PD) in 3 vs 4 patients; 4 and 2 patients died, respectively. The 24-month follow-up results were SD in nine vs ten patients, RD in one patient vs none and PD in four patients in both groups; three and four patients died, respectively. Side effects were rare and mild. The results indicate that therapy with tandem radioisotopes ({sup 90}Y/{sup 177}Lu-DOTATATE) provides longer overall survival than with a single radioisotope ({sup 90}Y-DOTATATE) and the safety of both methods is comparable. (orig.)

  18. 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.)

  19. 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

  20. 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

  1. Cross sections of deuteron induced reactions on $^{nat}$Sm for production of the therapeutic radionuclide $^{145}$Sm and $^{153}$Sm

    CERN Document Server

    Tárkányi, F; Takács, S; Ditrói, F; Csikai, J; Ignatyuk, A V

    2014-01-01

    At present, targeted radiotherapy (TR) is acknowledged to have great potential in oncology. A large list of interesting radionuclides is identified, including several radioisotopes of lanthanides, amongst them $^{145}$Sm and $^{153}$Sm. In this work the possibility of their production at a cyclotron was investigated using a deuteron beam and a samarium target. The excitation functions of the $^{nat}$Sm(d,x)$^{145153}$Sm reactions were determined for deuteron energies up to 50 MeV using the stacked-foil technique and high-resolution $\\gamma$-ray spectrometry. The measured cross sections and the contributing reactions were analyzed by comparison with results of the ALICE, EMPIRE and TALYS nuclear reaction codes. A short overview and comparison of possible production routes is given.

  2. Experimental cross section for the {sup 152}Sm(n, γ){sup 153}Sm reaction at 0.0334 eV

    Energy Technology Data Exchange (ETDEWEB)

    Uddin, M. Shuza; Datta, Tapash Kumar; Hossain, Syed Mohammod; Zakaria, A.K.M.; Islam, Mohammad Amirul; Naher, Kamrun; Shariff, M. Asad; Yunus, S.M. [Atomic Energy Research Establishment, Dhaka (Bangladesh). Inst. of Nuclear Science and Technology; Afroze, Nasmin [Atomic Energy Research Establishment, Dhaka (Bangladesh). Inst. of Nuclear Science and Technology; Jahangirnagar Univ., Dhaka (Bangladesh). Dept. of Physics; Islam, S.M. Ajharul [Jahangirnagar Univ., Dhaka (Bangladesh). Dept. of Physics

    2014-10-01

    The neutron capture cross section for the {sup 152}Sm(n, γ){sup 153}Sm reaction at an energy of 0.0334 eV was measured for the first time using monochromatic neutrons of a powder diffractometer at the TRIGA Mark II nuclear reactor at Dhaka, Bangladesh. The {sup 197}Au(n, γ){sup 198}Au reaction was used to monitor the neutron beam intensity. The radioactivity of the products was determined via high resolution γ-ray spectrometry. The obtained cross section value is 184 ± 22b, which is consistent with both the ENDF/B-VII and TENDL-2012 data libraries. The measured value at 0.0334 eV and the previous data at 0.0536 eV confirm the reliability of the data in the above libraries. (orig.)

  3. A comparative study of 51Cr releasing assay and lymphocyte colony inhibition test for detecting LAK activity

    International Nuclear Information System (INIS)

    51Cr releasing assay is widely used for detecting cytotoxicity. The correlation coefficient between 51Cr and traditional cyto-colony inhibition test is 0.9915(p51Cr releasing assay is considered to be much simpler and quicker, also can be recommended to be used in clinical practice

  4. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with (177)Lu-DOTATATE.

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium ((177)Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with (177)Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites

  5. Metastatic Neuroendocrine Tumor with Extensive Bone Marrow Involvement at Diagnosis: Evaluation of Response and Hematological Toxicity Profile of PRRT with 177Lu-DOTATATE

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

    The aim of this study was to evaluate the response and hematological toxicity in peptide receptor radionuclide therapy (PRRT) with lutetium (177Lu)-DOTA-octreotate (DOTATATE) in metastatic neuroendocrine tumor (NET) with extensive bone marrow metastasis at the initial diagnosis. A retrospective evaluation was undertaken for this purpose: Patients with NET with extensive diffuse bone marrow involvement at diagnosis who had received at least three cycles of PRRT with 177Lu-DOTATATE were considered for the analysis. The selected patients were analyzed for the following: (i) Patient and lesional characteristics, (ii) associated metastatic burden, (iii) hematological parameters at diagnosis and during the course of therapy, (iv) response to PRRT (using a 3-parameter assessment: Symptomatic including Karnofsky/Lansky performance score, biochemical finding, and scan finding), (v) dual tracer imaging features [with somatostatin receptor imaging (SRI) and fluorodeoxyglucose-positron emission tomography/computed tomography (FDG-PET/CT)]. Based on the visual grading, tracer uptake in somatostatin receptor (SSTR)-positive bone marrow lesions were graded by a 4-point scale into four categories (0-III) in comparison with the hepatic uptake on the scan: 0 - no uptake; I - clear focus but less than liver uptake; II - equal to liver uptake; and III - higher than liver uptake]. Hematological toxicity was evaluated using National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 score. A total of five patients (age range: 26-62 years; three males and two females) with diffuse bone marrow involvement at the diagnosis was encountered following analysis of the entire patient population of 250 patients. Based on the site of the primary, three had thoracic NET (two patients bronchial carcinoid and one pulmonary NET) and two gastroenteropancreatic NET (one in the duodenum and one patient of unknown primary with liver metastasis). Associated sites of

  6. Evaluation of 177Lu-DOTA-labeled aglycosylated monoclonal anti-L1-CAM antibody chCE7: influence of the number of chelators on the in vitro and in vivo properties

    International Nuclear Information System (INIS)

    Introduction: In this study, we optimized the 1,4,7,10-tetraazacyclododecane-N-N'-N''-N''''-tetraacetic acid (DOTA) chelator-to-antibody (c/a) ratio for the aglycosylated variant of the anti-L1-CAM antibody chCE7 (chCE7agl), providing high specific activity and low liver uptake in 177Lu-labeled form. Methods: chCE7agl was substituted with increasing molar excess of DOTA-NCS. The number of chelators coupled to the antibody and the binding affinities to target tumor cells (IC5 values) of the resulting immunoconjugates were determined. The different immunoconjugates were labeled with 177Lu; specific activity was measured, and metabolic stability was analyzed in human plasma. The effect of different c/a ratios on blood clearance and liver uptake was tested in nude mice. Changes of the protein backbone structure were analyzed by circular dichroism spectroscopy. Results: chCE7agl was substituted with 7, 12 or 15 DOTA ligands. The IC5 concentrations displacing radioiodinated chCE7 antibody increased with the number of chelators (1.5-fold with 7 ligands, 2.5-fold with 12 ligands and a 5-fold increase with 15 ligands). The highest specific activity for 177Lu-DOTA-chCE7agl was obtained with a c/a ratio of 12 (106 MBq/mg). Radioimmunoconjugates were stable in human plasma for at least 24 h. Blood clearance and liver uptake were measured after 24 h (c/a ratios of 12 and 15) or 48 h (c/a ratio of 7). The liver-to-blood ratios were 0.35±0.14 (7 ligands), 0.77±0.19 (12 ligands) and 17.85±3.44 (15 ligands). Conclusions: DOTA-chCE7agl conjugates with a c/a ratio of 12 combined high specific activity with good in vitro and in vivo properties. The rapid elimination rate from the blood and the high uptake in the liver of chCE7agl substituted with 15 DOTA ligands were found not to be due to conformational changes of the antibody backbone structure

  7. Radionuclide Treatment with 153Sm-EDTMP is Effective for the Palliation of Bone Pain in the Context of Extensive Bone Marrow Metastases: A Case Report

    Directory of Open Access Journals (Sweden)

    Kalevi Kairemo

    2014-10-01

    Full Text Available Radionuclide therapy is widely used as an effective modality in the management of bone pain. The main indication for this treatment is symptomatic bone metastases, confirmed by bone scintigraphy. We present a case of small cell lung cancer (SCLC stage T4N2M1b, with a good metabolic response to systemic therapy and radiotherapy of the primary tumor and locoregional disease, which became metabolically less active and remarkably smaller in size (reduction to 1/6 of the original volume. In spite of the good overall response, the patient developed a syndrome with severe bone pain and had progression in the bone marrow metastases, confirmed by 18F-FDG PET/CT. The patient received 153Sm-EDTMP treatment with a good clinical response. However, in the whole body bone scan with the therapeutic dose, there was no visual evidence of bone metastasis. Retrospectively, by drawing the region of interest, it was possible to identify one metastatic site. The possible mechanisms of the efficacy of this treatment modality, in this specific setting, are also discussed.

  8. Radionuclide Treatment with 153Sm-EDTMP is Effective for the Palliation of Bone Pain in the Context of Extensive Bone Marrow Metastases: A Case Report

    Science.gov (United States)

    Kairemo, Kalevi; Rasulova, Nigora; Suslaviciute, Justina; Alanko, Tuomo

    2014-01-01

    Radionuclide therapy is widely used as an effective modality in the management of bone pain. The main indication for this treatment is symptomatic bone metastases, confirmed by bone scintigraphy. We present a case of small cell lung cancer (SCLC) stage T4N2M1b, with a good metabolic response to systemic therapy and radiotherapy of the primary tumor and locoregional disease, which became metabolically less active and remarkably smaller in size (reduction to 1/6 of the original volume). In spite of the good overall response, the patient developed a syndrome with severe bone pain and had progression in the bone marrow metastases, confirmed by 18F-FDG PET/CT. The patient received 153Sm-EDTMP treatment with a good clinical response. However, in the whole body bone scan with the therapeutic dose, there was no visual evidence of bone metastasis. Retrospectively, by drawing the region of interest, it was possible to identify one metastatic site. The possible mechanisms of the efficacy of this treatment modality, in this specific setting, are also discussed. PMID:27408870

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

    International Nuclear Information System (INIS)

    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 177Lu-or 86Y-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 177Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm3) 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-mm3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten 86Y-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.)

  10. 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.)

  11. 51Cr-EDTA: a marker of early intestinal rejection in the rat

    International Nuclear Information System (INIS)

    Intestinal permeability was studied after accessory intestinal transplantation in Lewis rats. Five groups were evaluated: Group 1--isografts (N = 6); Group 2--Lewis X Brown Norway F1 (LBN-F1) allografts (N = 6); Group 3--isografts treated with CsA 2 mg/kg/day X 10 days (N = 6); Group 4--LBN-F1 allografts treated with CsA 2 mg/kg/day X 10 days (N = 6); Group 5--LBN-F1 allografts treated with CsA 4 mg/kg/day X 28 days (N = 6). Chromium-labeled ethylenedimianetetraacetate (51Cr-EDTA) was given through the proximal stoma of the graft. Renal clearance of 51Cr-EDTA and mucosal biopsies were followed post-transplant. The biopsies of the intestinal graft showed no rejection in Groups 1, 3, and 5; fulminant rejection in Group 2; and mild atypical rejection in Group 4. 51Cr-EDTA clearance was elevated in all groups during the first 7 days post-transplant. Thereafter, 51Cr-EDTA excretion fell to lower levels in the animals with histologically normal grafts (Groups 1, 3, and 5). 51Cr-EDTA excretion in Group 4 was increased with the first histological evidence of rejection on Day 14 and remained elevated until sacrifice (P less than 0.02 compared to Groups 3 and 5). A transient permeability defect occurs after intestinal grafting. Once the graft has recovered from this injury, 51Cr-EDTA is a sensitive marker for intestinal rejection

  12. 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

    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...... renal dysfunction (estimated clearance values below 21 ml/min) may be determined with adequate precision by one plasma sample drawn at 24 h after injection of the tracer without sampling at 5 h. This appears to be a very practical simplification....

  13. Assessment of mineral dust cytotoxicity toward rat alveolar macrophages using a 51Cr release assay

    International Nuclear Information System (INIS)

    An assay was developed to assess the cytotoxicity of mineral dust by measuring release of 51Cr from prelabeled rat alveolar macrophages. Optimal conditions for the assay are described, the most notable being use of 2% albumin instead of fetal calf serum. The assay demonstrated loss of label into the supernatant when prelabeled macrophages were cultured with the two pathogenic mineral dusts, quartz and chrysotile asbestos. In contrast the inert mineral dust titanium dioxide had very little effect on 51Cr release by rat alveolar macrophages

  14. 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...

  15. Study of the /sup 51/Cr release assay system in micro-method

    Energy Technology Data Exchange (ETDEWEB)

    Kiya, K.; Harada, K.; Uozumi, T. (Hiroshima Univ. (Japan). School of Medicine); Toge, T.; Hattori, T.

    1981-05-01

    Conditions of /sup 51/Cr release assay in microculture were investigated to measure the natural cytotoxic (NC) activity of mouse spleen cells. Malignant glioma (MG) cells of C57BL/6 mouse, induced by 20-methylcholanthrene, were labeled with Na/sub 2//sup 51/CrO/sub 4/. Spleen cells collected from the same mouse strain were suspended in Eagle's MEM. Labeled MG cells and spleen cells were incubated for several hours in a CO/sub 2/ incubator. Then the activity of the supernatant was measured by an automatic gamma counter. The optimum conditions of /sup 51/Cr release assay in micro-culture were, (1) number of the target cells: 5 x 10/sup 3// well (2) FCS concentration: 10% (3) E/T ratio: less than 100 : 1, 50 : 1 was possible (4) incubation time: 15 hours. The number of the target cells at labeling incubation was set to 2 x 10/sup 6//ml. Though the natural release of /sup 51/Cr was not effected by the viability of the target cells, it was suggested that the NC activity was dependent on the viability of both cells, target and effector cells.

  16. Conventional measurements of GFR using 51Cr-EDTA overestimate true renal clearance by 10 percent

    International Nuclear Information System (INIS)

    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 (51Cr-EDTA) is a gold standard method for determining glomerular filtration rate (GFR). However, there are reports that 51Cr-EDTA may have a significant extrarenal clearance. The aim of this study was to identify the non-renal component of 51Cr-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 51Cr-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 51Cr-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, α0, and the residual urine volume, ΔV. The results were α0=0.910 (95% CI: 0.889-0.932) and ΔV=14 ml (95% CI: -4 to +34 ml). The overestimation of the true renal clearance of 51Cr-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 51Cr-EDTA overestimate the true renal clearance of tracer by approximately 10%. (orig.)

  17. Evaluation of the radiosensitizing to treatment with 153Sm-EDTMP, of haematopoietic cells of the bone marrow by means of bromodeoxyuridine incorporation into DNA, in a murine model

    International Nuclear Information System (INIS)

    Bromodeoxyuridine (BrdU) has been shown to have a radiosensitizing effect, and its incorporation into DNA prior to administration of a bone-seeking radiopharmaceutical could increase the efficiency of bone marrow ablation, and even increase the specificity of radiation exposure for therapeutic purposes. The aim of the present study was to determine the effect of BrdU incorporation into DNA on the genotoxic and cytotoxic effects of samarium-153 ethylenediaminetetra-methylene phosphonate (153Sm-EDTMP) in murine bone marrow cells. BALB/c male mice (N = 5 in each experiment) were treated with one of the following substances: a) BrdU (0.25 mg/g) b) 153-EDTMP (11.5 ± 3 MBq) c) BrdU (0.25 mg/g) plus 153Sm-EDTMP (11.5 ± MBq), there was also an untreated control. Cytotoxicity and genotoxicity were established by time-response and absorbed dose-response curves of polychromatic erythrocyte (PCE) and micro nucleated polychromatic erythrocyte (MN-PCE) frequencies, respectively, in murine peripheral blood samples in vivo. The significance of the differences between groups was determined by a variation of Dunett test for multiple groups and different-sized groups of a student test. Beta-absorbed dose fractions obtained from MNCP4B Monte Carlo computer code were used for mice bone marrow dosimetry calculations. At an average radiation absorbed dose of 0.38 Gy, 0.56 Gy and 0.82 Gy at 24, 40 and 72 h respectively, cells from animals treated with 153Sm-EDTMP showed a clear and significant induction of MN-PCE after 24 h, with the maximum response at 40 h, however, cells from group treated with BrdU plus 153Sm-EDTMP paradoxically showed MN-PCE frequencies only slightly higher than the control at the same absorbed dose. Treatment with 153Sm-EDTMP caused a slight reduction in PCE frequency, but exposure to BrdU or BrdU plus 153Sm-EDTMP induced a substantial and significant reduction in PCE frequency from 32 h to the end of the experiment (72 h). The PCE frequencies in the Brd

  18. Evaluation of the radiosensitizing to treatment with {sup 153}Sm-EDTMP, of haematopoietic cells of the bone marrow by means of bromodeoxyuridine incorporation into DNA, in a murine model; Evaluacion de la radiosensibilizacion al tratamiento con {sup 153}Sm-EDTMP, de las celulas hemotopoyeticas de la medula osea mediante la incorporacion de bromodesoxiuridina (BrdU) en el ADN, en un modelo murino

    Energy Technology Data Exchange (ETDEWEB)

    Morales A, E.

    2008-07-01

    Bromodeoxyuridine (BrdU) has been shown to have a radiosensitizing effect, and its incorporation into DNA prior to administration of a bone-seeking radiopharmaceutical could increase the efficiency of bone marrow ablation, and even increase the specificity of radiation exposure for therapeutic purposes. The aim of the present study was to determine the effect of BrdU incorporation into DNA on the genotoxic and cytotoxic effects of samarium-153 ethylenediaminetetra-methylene phosphonate ({sup 153}Sm-EDTMP) in murine bone marrow cells. BALB/c male mice (N = 5 in each experiment) were treated with one of the following substances: a) BrdU (0.25 mg/g) b) {sup 153}-EDTMP (11.5 +- 3 MBq) c) BrdU (0.25 mg/g) plus {sup 153}Sm-EDTMP (11.5 +- MBq), there was also an untreated control. Cytotoxicity and genotoxicity were established by time-response and absorbed dose-response curves of polychromatic erythrocyte (PCE) and micro nucleated polychromatic erythrocyte (MN-PCE) frequencies, respectively, in murine peripheral blood samples in vivo. The significance of the differences between groups was determined by a variation of Dunett test for multiple groups and different-sized groups of a student test. Beta-absorbed dose fractions obtained from MNCP4B Monte Carlo computer code were used for mice bone marrow dosimetry calculations. At an average radiation absorbed dose of 0.38 Gy, 0.56 Gy and 0.82 Gy at 24, 40 and 72 h respectively, cells from animals treated with {sup 153}Sm-EDTMP showed a clear and significant induction of MN-PCE after 24 h, with the maximum response at 40 h, however, cells from group treated with BrdU plus {sup 153}Sm-EDTMP paradoxically showed MN-PCE frequencies only slightly higher than the control at the same absorbed dose. Treatment with {sup 153}Sm-EDTMP caused a slight reduction in PCE frequency, but exposure to BrdU or BrdU plus {sup 153}Sm-EDTMP induced a substantial and significant reduction in PCE frequency from 32 h to the end of the experiment (72 h

  19. 153 Sm-EDTMP骨摄取率测定及其与疗效的关系%Samarium-153-EDTMP bone uptake rate and its relation to therapeutic effect

    Institute of Scientific and Technical Information of China (English)

    李林; 梁正路; 邓候富; 匡安仁; 谭天秩; 罗顺忠

    2002-01-01

    Objective To evaluate the measurement of Samarium-153 ethylenediaminetetramethylene phosphonic acid (153Sm-EDTMP) bone uptake rate using whole-body scintigraphy and analyze the relationship between bone uptake rate and therapeutic effect. Methods Sixty-six patients with painful bony metastases from prostate (n=15), lung (n=20), breast (n=18), nasopharyngeal carcinoma (NPC) (n=5), colon (n=2), kidney (n=2) and unknown cause (n=4) carcinoma were examined with whole-body scintigraphy 10 min and 5 h post administration of 153 Sm-EDTMP. Bone uptake rate was then calculated. (1) Complete response (CR): disappearance of >2 metastases, Karnofsky Performance Score (KPS) increase >20, moderate or complete remission of bone pain 7 d post injection of 153 Sm-EDTMP. (2) Partial response (PR): disappearance of 1-2 metastases, KPS increase 10-20, moderate remission of bone pain in 3 wk. (3) Non-response (NR): no disappearance or shrinkage of metastases, KPS increase <10, no or slight remission of bone pain.Results The range of bone uptake rate in 66 patients was 31.9%-86.6% (mean=56.0%). The bone uptake rate in the CR group (17 cases, 25.7%), PR group (24 cases, 36.4%), and NR group (25 cases, 37.9%) was 52.4%-86.6% (mean=68.7%), 43.7%-70.4% (mean=58.3%), and 31.9%-51.5% (mean=41.0%) respectively. Statistical analysis showed that there was a significant difference between the CR and PR groups (t=4.258, P=0.001) as well as between PR and NR groups (t=8.48, P=0.001). Conclusions Using a simple and reliable whole-body scintigraphic technique to calculate prospectively the bone uptake rate, we have, for the first time in China, reported the relationship between bone uptake rate and therapeutic effect. This allows nuclear medicine physicians to calculate a safe and effective dose of 153 Sm-EDTMP in individual patients to palliate bone cancer pain without myelotoxicity.%目的在国内首次采用全身显像法测定153Sm-EDTMP(乙二胺四甲撑膦酸)骨摄取率并探讨骨摄取

  20. Intestinal permeability to [51Cr]EDTA in children with cystic fibrosis

    International Nuclear Information System (INIS)

    Intestinal permeability was investigated in 14 children with cystic fibrosis making use of [51Cr]EDTA as probe molecule. Ten normal young adults and 11 children served as controls. After oral administration of [51Cr]EDTA, 24 h urine was collected. Urinary radioactivity was calculated and results expressed as percentage of oral dose excreted in 24 h urine. Mean and SEM were as follows: 2.51 +/- 0.21, 2.35 +/- 0.24, and 13.19 +/- 1.72 for control children, normal adults, and cystic fibrosis patients, respectively. The permeability differences between cystic fibrosis patients and either control children or control adults are significant (p less than 0.001)

  1. 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.

  2. Burn-up cross sections of 51Cr, 59Fe, 65Zn, 86Rb, 103Ru

    International Nuclear Information System (INIS)

    Targets of Cr, Fe, Zn, Rb, and Ru were irradiated in the hydraulic tube of the Oak Ridge HFIR reactor at a neutron flux of 2.6 x 1015 n/cm2sec for 1 day and 20 days. The reactor burn-up cross sections (in barns) of the radioactive product nuclides are: 51Cr, 59Fe, 65Zn, 60 +- 30; 86Rb, 103Ru, <20

  3. Instant capture of recoil 51Cr(III) from neutron activated K2CrO4

    International Nuclear Information System (INIS)

    A new method of measuring the initial 51Cr(III) produced from nuclear recoil of K2CrO4 was developed. In this method K2CrO4 was mixed with MgO in the presence of a small amount of water, and the mixture was irradiated in a nuclear reactor. After irradiation, the mixture was dissolved in water, and MgO precipitate was separated from the solution. The yield of recoil 51Cr(III) could be calculated from the 51Cr activity in the precipitate measured. On the other hand, the yield of retention of 51Cr as chromate could be calculated from the activity found in the supernatant. The 51Cr(III) yield thus obtained is almost a factor of 2 higher than observed in pure K2CrO4 without mixing with MgO, irradiated under the same condition. Another important observation is that the 51Cr(III) yield is independent of irradiation time in presence of MgO. Without MgO the observed 51Cr(III) yield decreases with increasing irradiation time, suggesting possible oxidation of Cr(III) to chromate during irradiation. This variation is not observed in the system of K2CrO4 containing MgO, indicating that the initial Cr(III) is adsorbed immediately after nuclear recoil by MgO and is protected from oxidation by gamma radiation. (author) 4 refs.; 4 figs.; 2 tabs

  4. Studies with nonradioisotopic sodium chromate. II. Single- and double-label 52Cr/51Cr posttransfusion recovery estimations

    International Nuclear Information System (INIS)

    A recently developed nonradioisotopic 52Cr technique was used to measure either red cell volume or posttransfusion recovery of stored red cells. The experimental method uses Zeeman electrothermal atomic absorption spectrophotometry to measure red cell chromium. Results from the 52Cr method were compared with those from 51Cr single-label and 125I-albumin/51Cr double-label procedures using 49-day AS-1 red cell concentrates drawn and prepared according to standard procedures. In the first group of five donors, red cell volume was estimated concurrently with both 52Cr-labeled fresh red cells and 125I-albumin. The latter measured plasma volume from which red cell volume was estimated on the basis of the hematocrit (125I red cell volume). 51Cr-labeled stored red cells were transfused to measure posttransfusion recoveries. The correlation between 52Cr and 125I red cell volumes was significant (r = 0.68, p less than 0.01), and, in this group, the differences were not significant (p less than 0.05). Twenty-four-hour posttransfusion recoveries of 51Cr-labeled stored red cells averaged 66 +/- 5 percent when measured with the 125I/51Cr technique and 69 +/- 8 percent when measured with the 52Cr/51Cr method. In the second group of five donors, red cell volume was estimated by the 125I-albumin technique, and the posttransfusion recovery of stored red cells was quantitated by 51Cr- and 52Cr-labeled stored cells simultaneously. In this group, posttransfusion recoveries with 125I/51Cr averaged 73 +/- 7 percent; with 125I/52Cr, they averaged 75 +/- 10 percent. Using the single-label method of calculation, recoveries averaged 76 +/- 7 and 75 +/- 10 percent for the 51Cr and 52Cr methods, respectively

  5. 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.

  6. 153Sm-lexidronam for augmentation of chemotherapy-based myeloablative regimes in patients with multiple myeloma and other haematological conditions undergoing bone marrow transplantation: a phase I dose-escalation trial

    International Nuclear Information System (INIS)

    Full text: Total body irradiation (TBI) is a useful conditioning regimen for bone marrow transplantation (BMT), but has unacceptable toxicity in some patients. High doses of bone-seeking radiopharmaceuticals may offer a useful alternative to TBI in BMT patients with marrow-based tumours. Nine patients (5 multiple myeloma [MM], 2 leukaemia, 1 lymphoma, I myelodysplasia) were enrolled in a dose escalation protocol based upon retained skeletal activity. Infused doses have ranged between 18 and 32 GBq of 153Sm-EDTMP in six patients treated. No adverse effects related to the infusion have been seen. Peripheral blood counts fell from day 7 post-treatment, persisting to the start of cytotoxic conditioning regimen at days 11-14 post-treatment. Five patients have engrafted, with one allogeneic transplant patient dying from acute rejection. Pre-treatment dosimetry was performed by gamma camera and whole-body probe counts. Post-therapy activities were estimated by serial dose meter readings and gamma camera images. The pre-treatment skeletal retention by gamma camera was 1.7-2.4 times the values based on probe data. Retained post-treatment skeletal activity predicted by dosimetry was significantly greater than that actually measured, confirmed in one case by urinary collection. This latter fact is most likely due to the nature of the interaction of 153Sm-EDTMP with bone at high doses

  7. Thermal neutron capture cross sections for the 152Sm(n,γ) 153Sm and 154Sm(n,γ) 155Sm reactions at 0.0536 eV energy

    Science.gov (United States)

    Uddin, M. S.; Chowdhury, M. H.; Hossain, S. M.; Latif, Sk. A.; Islam, M. A.; Hafiz, M. A.; Mubin, S. H.; Zakaria, A. K. M.; Yunus, S. M.; Azharul Islam, S. M.

    2008-11-01

    The neutron capture cross sections for the 152Sm(n,γ) 153Sm and 154Sm(n,γ) 155Sm reactions at 0.0536 eV neutron energy were measured using an activation technique based on the TRIGA Mark-II research reactor, relative to the reference reaction 197Au(n,γ) 198Au. The activity was measured nondestructively using gamma-ray spectroscopy. Our measured values at this neutron energy are the first ones and are compared with 1/ v based evaluated cross sections reported in the ENDF/B-VII and JENDL-3.3 libraries. The measured value for the 152Sm(n,γ) 153Sm reaction is 0.28% lower than JENDL-3.3 and 0.48% higher than ENDF/B-VII. Our value for the production of 155Sm is about 3% and 2.3% higher than the evaluated value with ENDF/B-VII and JENDL-3.3 at 0.0536 eV, respectively.

  8. 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.

  9. 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.

  10. Reversibility of increased intestinal permeability to 51Cr-EDTA in patients with gastrointestinal inflammatory diseases

    Energy Technology Data Exchange (ETDEWEB)

    Jenkins, R.T.; Jones, D.B.; Goodacre, R.L.; Collins, S.M.; Coates, G.; Hunt, R.H.; Bienenstock, J.

    1987-11-01

    Intestinal permeability in adults with inflammatory gastrointestinal diseases was investigated by measuring the 24-h urinary excretion of orally administered /sup 51/Cr-EDTA. Eighty controls along with 100 patients with Crohn's disease, 46 patients with ulcerative colitis, 20 patients with gluten-sensitive enteropathy, and 18 patients with other diseases were studied. In controls, the median 24-h excretion was 1.34%/24 h of the oral dose. Patients with Crohn's disease (median 2.96%/24 h), ulcerative colitis (median 2.12%/24 h), and untreated gluten-sensitive enteropathy (median 3.56%/24 h) had significantly elevated urinary excretion of the probe compared to controls (p less than 0.0001). Increased 24-h urinary excretion of /sup 51/Cr-EDTA had a high association with intestinal inflammation (p less than 0.0001). Test specificity and sensitivity were 96% and 57%, respectively. A positive test has a 96% probability of correctly diagnosing the presence of intestinal inflammation, whereas a negative test has a 50% probability of predicting the absence of disease.

  11. 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.

  12. Assessment of glomerular filtration rate utilizing subcutaneously injected 51Cr-EDTA.

    Science.gov (United States)

    Monteiro, M C; Alonso, G; Ajzen, H; Pereira, A B

    1994-11-01

    1. 51Cr-EDTA injected with lidocaine and epinephrine, as a subcutaneous button, is slowly absorbed, and a plasma level that is relatively stable can be maintained for a time sufficient to permit measurement of the renal clearance of EDTA, which is a measure of glomerular filtration rate (GFR). We studied this procedure in 32 normal volunteers and 24 patients with different glomerulopathies, comparing EDTA and creatinine clearances. In 20 patients these measurements were also compared with inulin clearance. 2. Creatinine clearance overestimates GFR due to tubular secretion of creatinine. This secretion is present even in patients with significantly reduced glomerular filtration rates. As a consequence, the lower the GFR the higher the overestimation will be. 3. A good correlation was obtained between the 51Cr-EDTA and inulin clearance: y(EDTA) = 4.21 + 0.88 x (inulin), r = 0.98. The procedure is simple to perform, and the radiotracer utilized is significantly less expensive than iothalamate. PMID:7549976

  13. Use of a /sup 51/Cr technique to detect gastrointestinal microbleeding associated with nonsteroidal antiinflammatory drugs

    Energy Technology Data Exchange (ETDEWEB)

    Lussier, A.; Arsenault, A.; Varady, J.; de Medicis, R.; Lussier, Y.; LeBel, E.

    1987-02-01

    Of techniques used to evaluate gastrointestinal (GI) bleeding, use of radiochromium (/sup 51/Cr)-tagged erythrocytes is the most quantitative and scientifically acceptable method. The value of this technique as well as systematic errors possible with its use are discussed. The medical literature concerning /sup 51/Cr evaluation of GI microbleeding with naproxen therapy is critically reviewed. We suggest that future studies using this technique be parallel, randomized, double-blind, and include a 1-week placebo baseline phase for all subjects. Treatment with nonsteroidal antiinflammatory drugs (NSAIDs) should last 3 to 4 weeks. A parallel group of subjects should receive placebo throughout the study. For valid statistical analyses, randomization must achieve baseline comparability of weight, height, age, and sex in the treatment groups. Data transformations may be necessary to satisfy the assumptions of the statistical model. Following these guidelines will enable investigators to better evaluate GI microbleeding during treatment with naproxen or other NSAIDs, and, hopefully, to establish the safety profiles of these drugs.37 references.

  14. 153 Sm-EDTMP显像测定骨摄取率在个体化治疗剂量计算中的应用%Dosimetry of 153 Sm-EDTMP therapy by preparative whole-body scintigraphy

    Institute of Scientific and Technical Information of China (English)

    李林; 梁正路; 邓候富; 李云春

    2001-01-01

    目的探讨153Sm-乙二胺四甲撑膦酸(EDTMP)全身显像法在个体化给药剂量计算中的价值。方法对20例骨转移癌患者进行153Sm-EDTMP显像,计算骨摄取率,并与尿液收集法进行比较。结果显像法与尿液收集法所测得的骨摄取率之间具有很好的相关性(r=0.93)。根据显像法计算的骨摄取率,给药剂量为1.40~2.27 GBq(平均1.90 GBq),骨髓吸收剂量为1.37~1.43 Gy(平均1.40 Gy)。按标准体重计算,则应给予的剂量为1.75~2.41 GBq(平均2.18 GBq),骨髓吸收剂量为1.37~2.27 Gy(平均1.63 Gy)。两种方法给药剂量之间差异有显著性(t=4.075, P=0.001),骨髓吸收剂量差异也有显著性(t=4.030, P=0.001)。结论骨转移癌患者治疗剂量按153Sm-EDTMP显像法测定的骨摄取率进行个体化给药,在达到治疗目的的同时,还可避免发生骨髓毒性反应,具有重要的临床价值。

  15. 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...... with both labels, the kinetics of isotope uptake in the liver were strikingly different. Thus, retention of 51Cr in the liver was very high compared to a much lower and only transient retention of 125I. A higher retention of non-tumor cell-associated 51Cr was also observed in most other organs, resulting...... 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...

  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. Evaluation of the surface contamination density with 51Cr by direct measurement method using a GM survey-meter

    International Nuclear Information System (INIS)

    It is difficult to detect a low level contamination with 51Cr using a scintillation survey-meter because background counting rate of the survey-meter is high and emitted rate of γ-rays (0.320 MeV) from 51Cr is less than 10%. We examined whether a surface contamination with 51Cr can be detected directly with a GM survey-meter. As the result, the detection efficiency and detection limit of the GM survey-meter against the surface contamination were more than 0.6%(4π) and 4.6 Bq/cm2, respectively. From measurement of transmittance of radiations from 51Cr against poly (vinylidene chloride) seat, it became clear that the majority (about 98%) of detected radiations with the GM survey-meter is characteristic X-rays. These results show that the GM survey-meter can be used as a detector to check a surface contamination with 51Cr in controlled area. (author)

  18. Mathematical analysis of /sup 51/Cr-labelled red cell survival curves in congenital haemolytic anaemias

    Energy Technology Data Exchange (ETDEWEB)

    Kasfiki, A.G.; Antipas, S.E.; Dimitriou, P.A.; Gritzali, F.A.; Melissinos, K.G.

    1982-04-01

    The parameters of /sup 51/Cr labelled red cell survival curves were calculated in 26 patients with homozygous ..beta..-thalassaemia, 8 with sickle-cell anaemia and 3 with s-..beta..-thalassaemia, using a non-linear weighted least squares analysis computer program. In thalassaemic children the calculated parameters denote that the shorting of the mean cell life is due to early senescence alone, while there is some evidence that in thalassaemic adults additional extracellular destruction mechanisms participate as well. Red cell survival curves from patients with sickle-cell anaemia and s-..beta..-thalassaemia resemble each other, while their parameters indicate an initial rapid loss of radioactivity, early senescence and the presence of extracellular red cell destruction factors.

  19. Mathematical analysis of 51Cr-labelled red cell survival curves in congenital haemolytic anaemias

    International Nuclear Information System (INIS)

    The parameters of 51Cr labelled red cell survival curves were calculated in 26 patients with homozygous β-thalassaemia, 8 with sickle-cell anaemia and 3 with s-β-thalassaemia, using a non-linear weighted least squares analysis computer program. In thalassaemic children the calculated parameters denote that the shorting of the mean cell life is due to early senescence alone, while there is some evidence that in thalassaemic adults additional extracellular destruction mechanisms participate as well. Red cell survival curves from patients with sickle-cell anaemia and s-β-thalassaemia resemble each other, while their parameters indicate an initial rapid loss of radioactivity, early senescence and the presence of extracellular red cell destruction factors. (orig.)

  20. 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.

  1. 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

    fluid-plasma activity ratio of [51Cr]EDTA increased throughout the investigation period (5h). The results suggest that [51Cr]EDTA equilibrates slowly with the peritoneal space which indicates that Clt will over-estimate the glomerular filtration rate by approximately 20 ml/min in patients with ascites....... 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....

  2. Preparation of High specific activity of 51 Cr by the Szilard-Chalmers effect on potassium chromate

    International Nuclear Information System (INIS)

    The 51 Cr enriched Cr3+ ions, which appear on putting into solution the potassium chromate irradiated with neutrons, are separated as chromium hydroxide. The CrO42- ions occluded by the precipitate are eliminated on re precipitating the hydroxide. The more convenient irradiation time to for the production of 51 Cr has been determined as the position of the maximum in the experimental curve P=f(t), where the time-dependent index P used is defined as the product of the number. (Author) 13 refs

  3. 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)

  4. 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)

  5. 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

  6. 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)

  7. Grain boundary self-diffusion of 51Cr in Fe-Cr-Ni alloys

    International Nuclear Information System (INIS)

    The grain boundary self-diffusion characteristics P=α.δ.Dg (α is the segregation factor, δ is the grain boundary width and Dg is the grain boundary diffusion coefficient) of 51Cr were measured in the two alloys Fe-18 Cr-12 Ni and Fe-21 Cr-31 Ni. Experiments were performed in the temperature range from 973 to 1223 K using the sectioning method. In the frames of experimental errors there was found no significant difference between the results for both alloys. The temperature dependence of the triple product P for both materials can be thus described by the Arrhenius-type equation P(Cr)=(1.17+2.1-0.75).10-10.exp {-(234±19)/RT} m3/s. Within the errors, P values obtained in this paper are identical with those obtained in previous work for diffusion of 59Fe and 63Ni in the same materials. For the diffusion of all three basic constituents in both alloys the following equation is proposed P (Fe, Ni, Cr)=(6.7+9.9-4.0).10-12.exp {-(207±17)/RT} m3/s. (orig.)

  8. 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

    BACKGROUND: The nephrotoxity of calcineurin inhibitors in lung-transplanted patients is well described, but previous studies have estimated rather than directly measured glomerular filtration rate (GFR). This study describes the decline of measured GFR in a large cohort of lung-transplanted patie......BACKGROUND: The nephrotoxity of calcineurin inhibitors in lung-transplanted patients is well described, but previous studies have estimated rather than directly measured glomerular filtration rate (GFR). This study describes the decline of measured GFR in a large cohort of lung......-transplanted patients from a national centre, and the correlation between measured and calculated GFR. METHODS: All lung-transplanted patients 1992-2004 (n = 390) were included in a longitudinal analysis. Seven patients were excluded due to retransplantation. Pre- and post-transplant parameters included (51)Cr......-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...

  9. Automatic control system for measuring currents produced by ionization chambers; Automatizacao de um sistema de medidas de correntes produzidas por camaras de ionizacao e aplicacao na calibracao do {sup 18}F e {sup 153}Sm

    Energy Technology Data Exchange (ETDEWEB)

    Brancaccio, Franco

    2002-07-01

    Ionization Chambers in current mode operation are usually used in Nuclear Metrology. Activity measurements are quickly performed by Ionization Chambers, with very good precision. For this purpose measurements of very low ionization currents, carried out by high quality instrumentation, are required. Usually, electrometers perform the current integration method under command of signals from an automation system, in order to reduce the measurement uncertainties. Among the measurement systems at the Laboratorio de Metrologia Nuclear (LMN) of IPEN, there are two ionization chamber systems. In the present work, an automation system developed for current integration measurements is described. This automation system is composed by software (graphic interface and control) and an electronic module connected to a microcomputer, by means of a commercial data acquisition card. Several test measurements were performed in order to determine the intrinsic uncertainty, linearity and stability of the system. Using calibrated radioactive solutions, the IG12/A20 chamber calibration factors for {sup 18}F and {sup 153}Sm were obtained, making possible to determine activities of these radionuclides. (author)

  10. Interactions of animal age and particle size with deposition and retention of inhaled 51Cr-labeled microspheres

    International Nuclear Information System (INIS)

    Newborn, juvenile, weanling, and adult rats were exposed to aerosols of 51Cr-labeled microspheres with AMADs of 0.91, 1.4, 2.3, 3.4, and 4.4 μm. Alveolar deposition was negligible in newborn rats for all particle sizes, and decreased to less than 6% at an AMAD of 2.3 μm in juveniles and weanlings, and an AMAD of 3.4 μm in adults

  11. Intestinal permeability assessed by 51Cr-EDTA in rats with CCl4 - induced cirrhosis Permeabilidade intestinal ao 51-Cr-EDTA em ratos com cirrose induzida por CCl4

    Directory of Open Access Journals (Sweden)

    Ana Regina L. Ramos

    2010-06-01

    Full Text Available CONTEXT: The straight relationship between cirrhosis and impaired intestinal barrier has not been elucidated yet. OBJECTIVES: To verify 51Cr-EDTA-intestinal permeability in rats with CCl4-induced cirrhosis and controls. METHOD: Fifty male Wistar rats weighing 150-180 g were separated in three groups: 25 animals received CCl4 0.25 mL/kg with olive oil by gavage with 12 g/rat/day food restriction for 10 weeks (CCl4-induced cirrhosis; 12 received the same food restriction for 10 weeks (CCl4-non exposed. Other 13 rats received indomethacin 15 mg/kg by gavage as positive control of intestinal inflammation. RESULTS: The median (25-75 interquartile range 51Cr-EDTA-IP values of cirrhotic and CCl4-non exposed rats were 0.90% (0.63-1.79 and 0.90% (0.60-1.52 respectively, without significant difference (P = 0.65. Animals from indomethacin group showed 51Cr-EDTA-IP, median 7.3% (5.1-14.7, significantly higher than cirrhotic and CCl4-non exposed rats (PCONTEXTO: A relação direta entre cirrose e alterações na barreira intestinal ainda não foi devidamente esclarecida. OBJETIVO: Verificar a permeabilidade intestinal ao 51Cr-EDTA em ratos com cirrose induzida por tetracloreto de carbono (CCl4 e controles. MÉTODO: Cinquenta ratos Wistar machos pesando 150-180 g foram separados em três grupos: 25 animais receberam CCl4 0,25 mL/kg diluído em óleo de oliva por gavagem com restrição dietética de 12 g/rato/dia por 10 semanas (grupo cirrose induzida por CCl4; 12 receberam a mesma restrição dietética por 10 semanas (grupo não exposto ao CCl4. Outros 13 ratos receberam indometacina 15 mg/kg por gavagem como controle positivo de inflamação intestinal. RESULTADOS: A mediana (intervalo interquartil 25-75 dos valores de permeabilidade intestinal ao 51Cr-EDTA dos grupos cirrose induzida por CCl4 e não exposto ao CCl4 foram 0,90% (0,63-1,79 e 0,90% (0,60-1,52, respectivamente, sem significância estatística (P = 0,65. Os animais do grupo indometacina

  12. 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...

  13. In Vivo Determination of Site and Rate of Insulin Catabolism Using the Double Tracer Technique with 51Cr And 131I

    International Nuclear Information System (INIS)

    Double labelling of a peptide with 51Cr and 125(131)I results in an isotopic ratio that changes when and where the molecule in vivo is catabolized. Intracellular hydrolysis of the peptide liberates the iodine into the iodine pool, whereas the chromium by virtue of being a multivalent ion enters a new linkage at the site of breakdown. The isotopic ratio at the site of breakdown alters concomitantly with the hydrolysis rate. Experiments with 51Cr- and 125I-labelled insulin in mice in vivo and in vitro showed the liver (not muscle), bone (including marrow) and thyroid gland to be the major site of insulin catabolism with a half-life of approximately 10 min. In eight normal persons and diabetic patients insulin catabolism was analysed by the whole body counter following an iv injection of 0.77-0.95 μg insulin labelled with 51Cr and 131I. Counts were taken simultaneously from the area of the liver, thyroid, thigh and posterior pelvis. Again, the.data indicated the liver as the site of insulin catabolism, the normal half-life being approximately 20 min. Iodine- labelled insulin was commercially supplied. 51Cr-labelled insulin, prepared according to the methods of Kavai and Kesztyüs, was analysed by immune precipitation and Sephadex G200 chromatography. In the countercurrent distribution the 51Cr insulin showed enhanced water solubility. (author)

  14. 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 177Lu- and 90Y-BR96 mAbs

    International Nuclear Information System (INIS)

    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 90Y- and 177Lu-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 177Lu and 12.5 Gy for 90Y. 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 weight, ranging from

  15. 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)

  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....../bronchiectasis or idiopathic pulmonary fibrosis were included in an analysis of renal function before and after LTx. The glomerular filtration rate (GFR) was measured using the (51)Cr-ethylenediaminetetra acetic acid plasma clearance single injection technique (mGFR) at baseline before transplantation and at 1, 2.......0001), acute renal failure within 2 weeks post-LTx (p = 0.0003), use of heart and lung machine (p = 0.04), and the use of ephedrine (p = 0.048), as well as increasing age, older than 18 years at LTx (p = 0.006). These data demonstrate that renal function, measured with an isotope method, decreases dramatically...

  17. 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).

  18. 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...... study was to evaluate the accuracy of this non-invasive method in children. We calculated GFR from (99m)Tc-diethylene triamine pentaacetic acid (DTPA) renography and compared with (51)Cr-EDTA plasma clearance of 29 children between the age of 1 month and 12 years (mean 4.7 years). The correlation...

  19. 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....

  20. 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 B;

    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...... 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...

  1. Investigation into feed utilization by fore-aged silver carp (Hypophthalmichthys molitrix) using double-marked algae (/sup 14/C and /sup 51/Cr)

    Energy Technology Data Exchange (ETDEWEB)

    Wessel, B.; Spittler, P.; Heerkloss, R. (Rostock Univ. (German Democratic Republic). Sektion Biologie)

    1982-01-01

    The blue-green alga Microcystis firma and two green algae, Dunaliella viridis and Chlorella vulgaris, were double-marked with /sup 14/C and /sup 51/Cr. The /sup 51/Cr was used as an indicator to measure the assimilation efficiency of fore-aged silver carp for radiocarbon. The assimilation efficiency values obtained were 89.0 +- 5.43% for M. firma, 61.3 +- 15.28% for D. viridis and 91.3 +- 2.22% for C. vulgaris.

  2. Evidence for absorption of kelp detritus by the ribbed mussel Aulacomya ater using a new /sup 51/Cr-labelled microsphere technique

    Energy Technology Data Exchange (ETDEWEB)

    Stuart, V.; Field, J.G.; Newell, R.C.

    1983-09-15

    A modification of the /sup 51/Cr:/sup 14/C twin-labelling technique is described in which the food source is labelled with /sup 14/C but the /sup 51/Cr is enclosed in a polymeric resin membrane and presented as microspheres of a similar diameter to the food particles. This eliminates the major uptake of /sup 51/Cr which is transferred to the ctenidia and palps of the suspension-feeding mussel Aulacomya ater (Molina) from detritus labelled with /sup 51/Cr. The results suggest that although bacterial cultures based on isolates of kelp bacteria can be absorbed with an efficiency of 67 to 70%, the debris itself is also absorbed with an efficiency of approximately 50%. The kelp debris, which forms an important component of the particulate matter potentially available for consumers, may thus represent an important source of carbon for the filter feeding community adjacent to kelp beds. In contrast to the results obtained in other studies with artificial food sources, the data for kelp debris suggest that A. ater is able to maintain a positive scope for grwoth at the concentrations of suspended organic matter which occur under natural conditions in the kelp bed environment.

  3. Determination of optimal sampling times for a two blood sample clearance method using (51)Cr-EDTA in cats.

    Science.gov (United States)

    Vandermeulen, Eva; De Sadeleer, Carlos; Piepsz, Amy; Ham, Hamphrey R; Dobbeleir, André A; Vermeire, Simon T; Van Hoek, Ingrid M; Daminet, Sylvie; Slegers, Guido; Peremans, Kathelijne Y

    2010-08-01

    Estimation of the glomerular filtration rate (GFR) is a useful tool in the evaluation of kidney function in feline medicine. GFR can be determined by measuring the rate of tracer disappearance from the blood, and although these measurements are generally performed by multi-sampling techniques, simplified methods are more convenient in clinical practice. The optimal times for a simplified sampling strategy with two blood samples (2BS) for GFR measurement in cats using plasma (51)chromium ethylene diamine tetra-acetic acid ((51)Cr-EDTA) clearance were investigated. After intravenous administration of (51)Cr-EDTA, seven blood samples were obtained in 46 cats (19 euthyroid and 27 hyperthyroid cats, none with previously diagnosed chronic kidney disease (CKD)). The plasma clearance was then calculated from the seven point blood kinetics (7BS) and used for comparison to define the optimal sampling strategy by correlating different pairs of time points to the reference method. Mean GFR estimation for the reference method was 3.7+/-2.5 ml/min/kg (mean+/-standard deviation (SD)). Several pairs of sampling times were highly correlated with this reference method (r(2) > or = 0.980), with the best results when the first sample was taken 30 min after tracer injection and the second sample between 198 and 222 min after injection; or with the first sample at 36 min and the second at 234 or 240 min (r(2) for both combinations=0.984). Because of the similarity of GFR values obtained with the 2BS method in comparison to the values obtained with the 7BS reference method, the simplified method may offer an alternative for GFR estimation. Although a wide range of GFR values was found in the included group of cats, the applicability should be confirmed in cats suspected of renal disease and with confirmed CKD. Furthermore, although no indications of age-related effect were found in this study, a possible influence of age should be included in future studies. PMID:20452793

  4. Change in Distribution of Heat-Treated 51Cr-Labelled Erythrocytes in the Spleen by Dynamic Digital Scintigraphy

    International Nuclear Information System (INIS)

    It is known that in the normal functioning of the spleen, those red cells which do not meet certain minimum requirements from the circulation are able to be removed. The fate of these cells in different normal and abnormal conditions, as well as the role played by the spleen, has been adequately studied since erythrocytes labelled with radioactive substances have been employed. Observations are presented on the changes in the distribution of heat-treated 51Cr-labelled erythrocytes in the spleen against time, by repeated digital scintigraphy during one hour. Heat-treated 51Cr-labelled erythrocytes were injected intravenously in 15 subjects (five normals, five with thalassaemia and five with other different haematological diseases). Measurements were done with a Pho-Gamma Scintillation Camera, connected with a 1600 word memory and an Ampex magnetic tape recorder. Blood samples were taken at first every five minutes, then at twenty- minute intervals for one hour. The results in counts/min were plotted on semilogarithmic paper. The data were collected at intervals of 5 min, digitized by the 1600 word memory and transferred to the magnetic tape recorder from which they could be played back at any time for further analysis. After the end of the study the data from the magnetic tape were printed by a fast digital printer as channel position X and Y and number of counts. The number of counts were transferred to linear millimetre paper in an X and Y format. Isocount lines were then drawn for different levels of activity and the total number of counts inside each isocount line was added and divided by the number of channels. The results are expressed as a mean value of counts in different areas of the spleen; a difference between the counts taken over the whole spleen and the counts of the hot area; and the ratio of the counts of the most hot area and the counts of the whole area of the spleen. The results are discussed. (author)

  5. Measurement of the response of a gallium metal solar neutrino experiment to neutrinos from a 51Cr source

    International Nuclear Information System (INIS)

    The neutrino capture rate measured by the Russian-American Gallium Experiment is well below that predicted by solar models. To check the response of this experiment to low-energy neutrinos, a 517 kCi source of 51Cr was produced by irradiating 512.7 g of 92.4%-enriched 50Cr in a high-flux fast neutron reactor. This source, which mainly emits monoenergetic 747-keV neutrinos, was placed at the center of a 13.1 ton target of liquid gallium and the cross section for the production of 71Ge by the inverse beta decay reaction 71Ga(νe,e-)71Ge was measured to be [5.55±0.60thinsp(stat)±0.32thinsp(syst)]x10-45thinspcm2. The ratio of this cross section to the theoretical cross section of Bahcall for this reaction is 0.95 ±0.12 (expt)-0.027+0.035 (theor) and to the cross section of Haxton is 0.87±0.11 (expt)±0.09 (theor). This good agreement between prediction and observation implies that the overall experimental efficiency is correctly determined and provides considerable evidence for the reliability of the solar neutrino measurement. copyright 1999 The American Physical Society

  6. Susceptibility of adherent versus suspension target cells derived from adherent tissue culture lines to cell-mediated cytotoxicity in rapid 51Cr-release assays

    International Nuclear Information System (INIS)

    Preparation of target cells from tissue culture lines which grow adherent to tissue culture vessels is often desirable for tests of cell-mediated cytotoxicity (CMC). In the present study the authors used cells derived from adherent tissue culture lines to compare the merits of suspension vs. adherent target cells in short-term 51Cr-release assays. Cytotoxic activity of murine spleen cells sensitized in vitro against allogeneic spleen cells or syngeneic sarcoma cells was tested with fibroblast or sarcoma target cells. In parallel tests, aliquots of tissue culture lines were detached and used as either suspension or adherent target cells in CMC assays, matching the concentrations of suspension and adherent target cells. In both allogeneic and syngeneic combinations adherent target cells released less 51Cr spontaneously and were more susceptible to CMC than their suspension counterparts. (Auth.)

  7. 177Lu-octreotate in Neuroendocrine Tumors: Treatment Effects

    NARCIS (Netherlands)

    E.I. van Vliet (Esther)

    2013-01-01

    textabstractNeuroendocriene tumoren (NETs) zijn zeer zeldzame tumoren, die ontstaan vanuit neuroendocriene cellen in het lichaam. Deze tumoren produceren vaak hormonen en hormoonachtige stoffen. NETs ontstaan meestal in het maag-darm kanaal, in de alvleesklier, of in de longen. Jaarlijks komen er in

  8. 177Lu-octreotate in Neuroendocrine Tumors: Treatment Effects

    OpenAIRE

    van Vliet, Esther

    2013-01-01

    textabstractNeuroendocriene tumoren (NETs) zijn zeer zeldzame tumoren, die ontstaan vanuit neuroendocriene cellen in het lichaam. Deze tumoren produceren vaak hormonen en hormoonachtige stoffen. NETs ontstaan meestal in het maag-darm kanaal, in de alvleesklier, of in de longen. Jaarlijks komen er in Nederland ongeveer 700 nieuwe NET-patiënten bij. De enige mogelijkheid om deze patiënten te genezen is om hen te opereren. Vaak kan dit echter niet meer, omdat de tumor al uitgezaaid is, of te gro...

  9. Comparative study of conventional PAH and inulin clearance and slope clearance of 131I-o-hippuric acid and 51Cr-EDTA

    International Nuclear Information System (INIS)

    ''Classic'' PAH and inulin clearance were determined in 81 patients with renal anomalies or renal diseases of different genesis and severity. In addition, radioisotope nephrography was carried out after administration of I-131-o-hippuric acid, followed by administration of Cr-51-EDTA. The activity decrease was recorded by a sensor located over the patient's right shoulder; the activities of a serum sample and of the urine excreted after 21 or 31 min were measured, and the findings were compared with those of the classic method. The clearance data calculated on the basis of the soulder measurements were hardly compatible with those of the conventional method in the case of 131I-o-hippuric acid (r=0.54) and totally incompatible in the case of 51Cr-EDTA. This means that the method described by Oberhausen is the only accurate method available for a quantitative assessment of the renal function on the basis of measurements of the activity decrease in the body. The activity of urine excreted after 31 min (131I-hippuric acid:r=0.992, 51Cr-EDTA:r=0.79) is a sufficiently accurate parameter although it is inaccurate at PAH clearance, values > 130 ml/min and inulin clearance values > 30 ml/min. Of the many parameters of radioisotope nephrogram curves, in the case of 131I-o-hippuric acid only the parameters related to the ascent between 48 and 120 sec or to the secant ascent yield sufficient quantitative information for certain functional regions (r=0.9 resp. r=0.93). In the case of 51Cr-EDTA, semiquantitative information on the renal function can be obtained by constructing secants on the nephrogram curves (r=0.7 resp. r=0.72). Here as in the case of 131I-hippuric acid, the contribution of each kidney can be determined individually from the functional analysis of both kidneys. (orig.)

  10. 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

  11. 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

  12. 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.

  13. Feasibility of the instrumental neutron activation analysis of entire archaeological pottery. Part 1: Precision of the results and radiological safety of the process

    International Nuclear Information System (INIS)

    The feasibility of the instrumental neutron activation analysis of entire pieces of archaeological pottery, using low thermal neutron fluxes, is examined. The study takes into account the chemical elements relevant for archaeological investigations, as well as the degree of accuracy required for such kind of research. It is shown that after irradiation of a typical pottery sample of about 1 kg during 45 minutes, at a thermal flux of about 109 n.cm-2.s-1, analytical signals are obtained, by gamma spectrometry, with counting statistics better than 1%, for 76As, 131Ba, 141Ce, 60Co, 134Cs, 181Hf, 140La, 24Na, 122Sb, 46Sc, 153Sm and 233Pa, whereas 51Cr, 152Eu, 42K, 86Rb, 175Yb and 65Zn can be detected with counting statistics within 1% and 2%. On the other hand, the statistics of measurement are relatively poor (orders of 3% - 10%) for 177Lu, 147Nd, 239Np, 160Tb and 181Ta. The feasibility of accomplishment reliable quantitative determinations, taking into account the complexity of the analysis of entire pieces of archaeological pottery is discussed, which involves factors such as high masses, as well as asymmetric and variable shapes. (orig.)

  14. Bioelimination of 51Cr and 85Sr by cockroaches, Gromphadorhina portentosa (orthoptera: blaberidae), as affected by mites, Gromphadorholaelaps schaeferi (parasitiformes: laelapidae)

    International Nuclear Information System (INIS)

    The rates of Chromium-51 and Strontium-85 assimilation and bioelimination by the hissing cockroach, Gromphadorhina portentosa (Schaum) are described when the symbiotic mite, Gromphadorholaelaps schaeferi Till, was present or removed. Mite-infested cockroaches had significantly higher rates of 51Cr elimination relative to mite-free cockroaches, implying more rapid gut clearance times. The authors did not find a significant mite effect on 85Sr elimination by the host, but mite effects could have been masked by the apparently unique process of nutrient assimilation and elimination by G. portentosa. Conventional models of radioactive tracer bioelimination predict a rapid initial loss of tracer due to gut clearance, followed by a slower loss due to excretion of assimilated tracer. The results indicated that assimilated 85Sr was eliminated earlier than unassimilated 85Sr, which was lost by defecation

  15. Bioelimination of 51Cr and 85Sr by cockroaches, Gromphadorhina portentosa (Orthoptera: Blaberidae), as affected by mites, Gromphadorholaelaps schaeferi (parasitiformes: laelapidae)

    International Nuclear Information System (INIS)

    This paper describes rates of Chromium-51 and Strontium-85 assimilation and bioelimination by the hissing cockroach, Gromphadorhina portentosa (Schaum), when the symbiotic mite, Gromphadorholaelaps schaeferi Till, was present or removed. Mite-infested cockroaches had significantly higher rates of 51Cr elimination relative to mite-free cockroaches, implying more rapid gut clearance times. We did not find a significant mite effect on 85Sr elimination by the host, but mite effects could have been masked by the apparently unique process of nutrient assimilation and elimination by G. portentosa. Conventional models of radioactive tracer bioelimination predict a rapid initial loss of tracer due to gut clearance, followed by a slower loss due to excretion of assimilated tracer. Our results indicated that assimilated 85Sr was eliminated earlier than unassimilated 85Sr was lost by defecation

  16. Levels of chromium contamination in the estuary of the Iraja river (Guanabara Bay) and experimental incorporation of 51Cr in barnacles (Balanus sp)

    International Nuclear Information System (INIS)

    Levels were determined of chromium contamination in the estuary of Iraja River, produced by an electroplating industry located 3 km upstream the study area. Uptake-and release kinetics of Cr(VI) and Cr(III) in barnacles (Balanus sp.) were studied. Samples of barnacles and suspended particles from Guanabara Bay were analysed. Chromium concentrations (dry weight) ranged from not detectable (ND) to 154,66 μg/g for soft tissues and from ND to 423,76 μg/g for suspended particles. Mean of maximum concentrations of chromium in samples from Guanabara Bay are 3 and 4 times above those of identical samples from control area (Coroa Grande). Soft tissues presented a concentration factor (CF) of 103 related to chromium available in suspended particles. 51Cr(VI) is preferentiably incorparated by soft tissues (biological half life being 100 days). Chromium uptake by Balanus sp from solution is as significant as it is from particulate matter available in sea water from experimental sets. CF for Cr(VI) in soft tissues in laboratory conditions was 102 related to 51Cr present in sea water. Environmental chromium contamination was found to be of the same order of magnitude or above levels reported for other areas subjected to industrial impacts. Barnacles appear to be able to accumulate chromium in soft tissues from the available metal in the environment. Cr(VI) is the critical form, being greatly accumulated in soft tissues of barnacles, that act as a long-term integrator of this metal. For Cr(III), this organism can only be regarded as an instantaneous indicator of environmental contamination of chromium attached to suspended particles. (M.A.)

  17. 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...... 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...

  18. 51Cr - erythrocyte survival curves

    International Nuclear Information System (INIS)

    Sixteen patients were studied, being fifteen patients in hemolytic state, and a normal individual as a witness. The aim was to obtain better techniques for the analysis of the erythrocytes, survival curves, according to the recommendations of the International Committee of Hematology. It was used the radiochromatic method as a tracer. Previously a revisional study of the International Literature was made in its aspects inherent to the work in execution, rendering possible to establish comparisons and clarify phonomena observed in cur investigation. Several parameters were considered in this study, hindering both the exponential and the linear curves. The analysis of the survival curves of the erythrocytes in the studied group, revealed that the elution factor did not present a homogeneous answer quantitatively to all, though, the result of the analysis of these curves have been established, through listed programs in the electronic calculator. (Author)

  19. 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.

  20. Investigation of the neutron activation of endohedral rare earth metallofullerenes

    International Nuclear Information System (INIS)

    Endohedral lanthanide metallofullerenes and their water-soluble biocompatible derivatives have been synthesized. The effect that fast-neutron irradiation has on the stability and nuclear physical properties of endohedral metallofullerenes that are used as magnetocontrast materials (46Sc, 140La, 141Nd, 153Sm, 152Eu, 154Eu, 153Sm, 160Tb, 169Yb, 170Tm (isomers I and III), and 177Lu) is studied. Our hypothesis, according to which carbon-shell relaxation is based on the fast nonradiative processes of an electron shake-off type, is confirmed.

  1. Effect of background region of interest and time-interval selection on glomerular filtration ratio estimation by percentage dose uptake of (99m)Tc-DTPA in comparison with (51)Cr-EDTA clearance in healthy cats.

    Science.gov (United States)

    Debruyn, Katrien; Vandermeulen, Eva; Saunders, Jimmy H; Dobbeleir, André A; Ham, Hamphrey R; Peremans, Kathelijne

    2013-08-01

    Evaluation of glomerular function is a useful part of the diagnostic approach in animals suspected of having renal disease. Time-interval and background region of interest (bg ROI) selection are determining factors when calculating the glomerular filtration ratio (GFR) based on percentage uptake of (99m)technetium-labelled diethylene triamine penta-acetic acid ((99m)Tc-DTPA). Therefore, three different time intervals (60-120 s, 120-180 s, 60-180 s) and three different bg ROIs (C-shape, caudolateral, cranial + caudal) were investigated. In addition, global GFRs based on percentage dose uptake of (99m)Tc-DTPA for the different time-intervals and bg ROIs were compared with the global GFR based on (51)chromium-ethylene diaminic tetra-acetic acid ((51)Cr-EDTA) plasma clearance in nine healthy European domestic shorthair cats. Paired Student's t-tests and linear regression analysis were used to analyse the data. Different time intervals seemed to cause significant variation (P <0.01) in absolute GFR values, regardless of the choice of bg ROI. Significant differences (P <0.01) between bg ROIs were only observed in the 120-180s time interval between the C-shape and cranial + caudal bg ROI, and between the caudolateral and cranial + caudal bg ROI. The caudolateral bg ROI in the 60-180 s time interval showed the highest correlation coefficient (r = 0.882) between (99m)Tc-DTPA and (51)Cr-EDTA, although a significant difference (P <0.05) was present between both techniques. PMID:23349527

  2. Subacute haematotoxicity after PRRT with 177Lu-DOTA-octreotate: prognostic factors, incidence and course

    NARCIS (Netherlands)

    H. Bergsma (Hendrik); M. Konijnenberg (Mark); B.L.R. Kam (Boen L. R.); J.J.M. Teunissen (Jaap); P.P.M. Kooij (Peter); W.W. de Herder (Wouter); G. Franssen (Gaston); C.H.J. van Eijck (Casper); E.P. Krenning (Eric); D. Kwekkeboom (Dik)

    2016-01-01

    textabstractPurpose: 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 131I treatment. We investigated the incidence and duration of haematological toxicity and its risk factors in patients t

  3. 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,

  4. 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.

  5. 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

  6. Treatment efficacy of 153Sm-EDTMP for painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Narjess Ayati

    2013-04-01

    Full Text Available Introduction: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. Methods: 28 patients (14 males and 14 females aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. Results: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8. 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%. The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. Conclusion: Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved.

  7. Treatment efficacy of 153Sm-EDTMP for painful bone metastasis

    Directory of Open Access Journals (Sweden)

    Narjess Ayati

    2013-04-01

    Full Text Available Introduction: Involvement of the skeleton can cause an excruciating pain in two-thirds of terminal patients with a history of malignancy. Due to several limitations of other therapies, such as analgesics, bisphosphonates, chemotherapy, hormonal therapy and external beam radiotherapy; bone-seeking radiopharmaceuticals have an important role in palliation of pain from bone metastases. Although these kinds of therapies have many advantages including the ability to treat multiple sites of tumoral involvement simultaneously, no significant confliction with other treatments, ease of administration and the potential to be used repetitively; in Iran using of this modality is not widely practiced. In this study we evaluated the clinical usefulness of Sm-153 lexidronamfor pain management of bone metastases. Methods: 28 patients (14 males and 14 females aged 38-77 years with a history of painful bone metastases caused by different cancers, not responding to conventional treatments were included in the study. All patients had a recent whole body bone scan indicating multiple bone metastases. 1 mCi/Kg Sm-153 lexidronam was injected intravenously to the patients. Whole body scintigraphy was done 3 or 18 hours post injection. Pain relief and quality of life have been evaluated by analog pain scale and Karnofsky index every week, respectively. Also, all patients were evaluated for hematological toxicity every two weeks. Active follow ups were performed. Results: 43% of patients showed the presence of the flare phenomenon during the first three days after Sm injection with a mean duration of 2.2 days. The pain relief began between 2 and 16 days post injection and the duration of pain palliation was in the range of 4 to 32 weeks (mean±SD=15.22±7.8. 64.3% of patients showed complete relief of pain and 21.4% achieved partial response to therapy. (Over all response to therapy was 85.7%. The lowest amount of peripheral blood cells was detected in the fourth week for RBCs and in the 6th week for WBCs and PLTs. No one experienced hematological toxicity induced problems. Conclusion:  Sm-153 lexidronam is an effective treatment for painful bone metastases. The complication rate is low and the quality of life of the patients after treatment would be significantly improved.

  8. Bone marrow dosimetry in peptide receptor radionuclide therapy with [ 177Lu-DOTA0,Tyr3]octreotate

    NARCIS (Netherlands)

    F. Forrer (Flavio); E.P. Krenning (Eric); P.P.M. Kooij (Peter); B.F. Bernard (Bert); M. Konijnenberg (Mark); W.H. Bakker (Willem); J.J.M. Teunissen (Jaap); M. de Jong (Marion); K. van Lom (Kirsten); W.W. de Herder (Wouter); D. Kwekkeboom (Dik)

    2009-01-01

    textabstractPurpose: 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 acc

  9. 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.)

  10. Measurement of the activity of the radiopharmaceuticals used in therapy

    Energy Technology Data Exchange (ETDEWEB)

    Sahagia, M.; Razdolescu, A.C.; Grigorescu, E.L.; Luca, A.; Ivan, C. [National Institute of R and D for Physics and Nuclear Engineering ' Horia Hulubei' IFIN-HH, POB MG-6, Bucharest (Romania)

    2006-07-01

    The paper presents the results obtained in the assurance of the whole traceability chain in the measurement of the activity for a particular group of radionuclides used as therapeutic pharmaceuticals: strong beta - weak gamma emitters, such as: 153 Sm, 177 Lu, 186 Re, 188 Re. The regulations regarding the uncertainty of the activity of therapy radiopharmaceuticals impose a maximum limit of 5%. All the above mentioned radionuclides belong to the group of triangular decay scheme and consequently they were standardized absolutely by the 4{pi}{beta}-{gamma} coincidence method. The solutions were then used for the calibration of the secondary standard, consisting from a 'Centronic I.G.12/20 A' ionization chamber. The calibration was transferred to the commercial radioisotope calibrators, as initial calibration figures. Some of these results are presented in the paper. (author)

  11. 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.

  12. Radiolanthanide-labeled HA particles in the treatment of rheumatoid arthritis. Ready-to-use cold kits for rapid formulation in hospital radiopharmacy

    International Nuclear Information System (INIS)

    Hydroxyapatite (HA) [Ca10(PO4)6(OH)2] particles radiolabeled with a variety of β- emitting lanthanide radionuclides and also pseudolanthanide 90Y have been proposed for the treatment of arthritis. A ready-to-use cold kit of HA particles (1-10 μm size) was developed for fast and convenient formulation of radiolanthanide-labeled HA particles at hospital radiopharmacy. Six radionuclides namely, 169Er, 177Lu, 153Sm, 166Ho, 142Pr and 90Y, having β- emissions of a wide range of energy [Eβ(max) = 0.34-2.28 MeV] were identified and produced by thermal neutron activation. Clinical doses of HA particles labeled with these radionuclides were prepared in high yield (>97 %) and radiochemical purity (>99 %) using the cold kits. Pre-clinical studies of 177Lu-HA carried out in Wistar rats bearing arthritis in knee joints revealed no leakage of the activity from the joints. In preliminary clinical investigation using 333 ± 46 MBq doses of the same preparation, significant improvement in the disease conditions was reported in patients with chronic rheumatoid arthritis of knee joints. (author)

  13. 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...

  14. 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...

  15. Relationship of tumor absorbed doses of 177Lu-DOTA-TATE treatment and uptake in pre-therapeutic Ga68 DOTA-TATE PET/CT imaging

    International Nuclear Information System (INIS)

    Full text of publication follows. Introduction/Background: Peptide Receptor Radionuclide Therapy (PRRT) with labeled Lu177 labeled peptide in patients with neuroendocrine tumors (NETs) aroused great interest. An estimation of actual radiation doses to tumors is very important for therapy planning. It is well known that uptake of Ga-68 DOTATATE very well correlated with sst2 expression. The uptake of radio-labelled peptides calculated from SUV max values may predict the radiation-absorbed dosimetry of lesions treated with PRRT. Aim: the aim of the study was to evaluate the relationship between the tumor absorbed doses and pre-therapeutic Ga68 DOTA-TATE PET/CT uptake calculated from SUV values. Materials and methods: PRRT results of patients (M/F: 8/5, mean age: 55.5 ± 12.5 years) with histologically proven inoperable NETs were retrospectively analyzed. Dosimetric calculations were performed using MIRD scheme and lesion doses were calculated using post therapy whole body images obtained at 4, 20, 44, and 68 hours after injection. Calculated tumor absorbed doses were compared with SUVmax of 68Ga-DOTA-TATE PET/CT, which were performed before the therapy. Tumor volumes were determined from CT images. Thirteen blood samples beginning from time zero to 4 days after injection were obtained for bone marrow and whole body dosimetry. Results: there were 38 lesions in 13 patients. Lesions were selected according to lesion delineation and superimposed lesions were excluded. Mean lesion volume was 19.58 ± 25 cm3. Median tumor dose for all lesions, bone lesions, lesions on other sites (lung, liver, lymph nodes) were 15.08 Gy, 19.34 Gy, 14.05 Gy per 370 MBq respectively. Median SUVmax values of those were 25.8, 13.7, 23.05, respectively. Correlation between calculated tumor dose and uptake of 68Ga-DOTA-TATE was moderate (R=0.42). Also a moderate correlation was found for radiation absorbed doses of bone metastases. A very low correlation was found for radiation absorbed doses of lung, liver and lymph nodes metastases. Conclusion: the uptake of radiolabelled peptides calculated from SUV max values may predict the radiation-absorbed dosimetry of lesions treated with PRRT and it may be used for prognostic evaluation and therapy outcome. (authors)

  16. 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

  17. The Influence of Linker Length on the Properties of Cathepsin S Cleavable 177Lu-labeled HPMA Copolymers for Pancreatic Cancer Imaging

    OpenAIRE

    Shi, Wen; Wagh, Nilesh K.; Zhou, Zhengyuan; Jia, Yinnong; Brusnahan, Susan K.; Garrison, Jered C.

    2014-01-01

    N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymers have shown promise for application in the detection and staging of cancer. However, non-target accumulation, particularly in the liver and spleen, hinders the detection of resident or nearby metastatic lesions thereby decreasing diagnostic effectiveness. Our laboratory has pursued the development of cathepsin S susceptible linkers (CSLs) to reduce the non-target accumulation of diagnostic/radiotherapeutic HPMA copolymers. In this study, we ...

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

    OpenAIRE

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

    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 ...

  19. 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.

  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. PMID:27496068

  1. 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.

  2. 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...

  3. Recent progress in radioisotope production in Vietnam

    Energy Technology Data Exchange (ETDEWEB)

    Le Van So [Radioisotope Dept., Nuclear Research Institute, Dalat (Viet Nam)

    1998-10-01

    This is a report on the recent progress in radioisotope production in Vietnam. Using a nuclear research reactor of 500 KW with continuous operation cycles of 100 hours a month, the production of some important radioisotopes used in nuclear medicine and research was routinely carried out. More than 80 per cent of irradiation capacity of reactor for radioisotope production were exploited. The radioactivity of more than 150 Ci of {sup 131}I, {sup 99}Mo-{sup 99m}Tc, {sup 32}P, {sup 51}Cr, {sup 153}Sm, {sup 46}Sc, {sup 192}Ir was produced annually. Radiopharmaceuticals such as {sup 131}I-Hippuran and in-vivo Kits for {sup 99m}Tc labelling were also prepared routinely and regularly. More than 10 in-vivo Kits including modern radiopharmaceuticals such as HmPAO kit were supplied to hospitals in Vietnam. The research on the improvement of dry distillation technology for production of {sup 131}I was carried out. As a result obtained a new distillation apparatus made from glass was successfully put to routine use in place of expensive quartz distillation furnace. We have also continued the research programme on the development of {sup 99m}Tc generators using low power research reactors. Gel technology using Zr- and Ti- molybdate gel columns for {sup 99m}Tc generator production was developed and improved continually. Portable {sup 99m}Tc generator using Zr-({sup 99}Mo) molybdate gel column and ZISORB adsorbent column for {sup 99m}Tc concentration were developed. The ZISORB adsorbent of high adsorption capacity for {sup 99}Mo and other parent radionuclides was also studied for the development purpose of alternative technology of {sup 99m}Tc and other different radionuclide generator systems. The studies on the preparation of therapeutic radiopharmaceuticals labelling with {sup 153}Sm and {sup 131}I such as {sup 153}Sm-EDTMP, {sup 131}I-MIBG were carried out. (author)

  4. 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)

  5. Produktion und chemische Aufarbeitung von Lu-177 für die Nuklearmedizin am Forschungsreaktor FRM-II in München

    OpenAIRE

    Dvorakova, Zuzana

    2010-01-01

    The goal of the thesis was to investigate the feasibility of producing the therapeutic radionuclide 177Lu at the reactor FRM-II. The irradiation yield of 177Lu in the direct (176Lu(n,gamma)177Lu) and the indirect (176Yb(n,gamma)177Yb beta- decay 177Lu) production routes was determined. A reliable method for the calculation of the 177Lu yield was established. The isomer 177mLu was confirmed to be the only relevant long-lived radionuclidic impurity found in product of the direct route. A proced...

  6. Contribution to the study of the biological properties of compounds labeled with radio-chromium 51Cr

    International Nuclear Information System (INIS)

    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)

  7. The effect of 51Cr-labelling on cell morphology, in vitro, when evaluating the cytotoxicity of endodontic filling materials

    International Nuclear Information System (INIS)

    Human periodontal ligament fibroblasts and L 929 cell line labelled with chromium 51 were examined byelectron microscope to evaluate the effect of the chromium labeling on the cell ultrastructure. The cells were labeled with chromium 12-20 hours before the start of the experiment. After two and four hours of incubation at 37 degree C and 100% humidity, the cells were examined by scanning and transmission electron microscopy. The result showed that the chromium labeling did not cause any morphological changes. (author)

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

    DEFF Research Database (Denmark)

    Aarkrog, Asker; Lippert, Jørgen Emil

    1971-01-01

    A study 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−0·31 g.cmstaggered−1, where g is the dry weight of the herbage in a plot in grammes, and cm the height of the plants at spraying...... activity in per cent 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....

  9. Production, quality control, biological evaluation and biodistribution modeling of Lutetium-177 maltolate as a viable bone pain palliative in skeletal metastasis

    International Nuclear Information System (INIS)

    177Lu-maltolate (177Lu-MAL) was successfully developed which can be widely used in bone palliation therapy. At optimized conditions a radiochemical purity of about >99 % was obtained for 177Lu-MAL shown by ITLC (specific activity, 970-1,000 MBq/mmole). Biodistribution studies of 177Lu chloride and 177Lu-MAL were carried out in wild-type rats comparing the critical organ uptakes. Compartmental analysis was used to determine temporal biodistribution model of 177Lu-MAL in different organs. 177Lu-MAL is a possible therapeutic agent in human malignancies for the bone palliation therapy so the efficacy of the compound should be tested in various animal models. (author)

  10. Alternative methods for radiochemical purity testing in radiopharmaceuticals

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, Ideli M. de; Martins, Patricia de A.; Silva, Jose L. da; Ramos, Marcelo P.S.; Lima, Jose A.S.; Pujatti, Priscilla B.; Fukumori, Neuza T.O.; Matsuda, Margareth M.N. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2011-07-01

    The radiochemical purity (RCP) testing is as prerequisite for radiopharmaceuticals before the administration to the patient. Because time is critical in nuclear medicine, emphasis should be given to the radiochemical quality control procedures, in order to obtain the maximum amount of information in the minimum period of time. Radiochemical purity is defined as the proportion of the total radioactivity in the product that is present in the specified chemical form. Usually, the RCP is evaluated by thin layer chromatography (TLC) and high performance liquid chromatography (HPLC). The most widely used technique for RCP determination in radiopharmaceutical preparations is TLC-aluminium (TLC-Al), instant thin layer chromatography-silica gel (ITLC-SG) and paper chromatography (PC). Indeed, many of the pharmacopeial methods use these techniques. The purpose of the present study was to evaluate different chromatographic systems for RCP in {sup 67}Ga-Citrate, {sup 111}In-Octreotide, {sup 177}Lu-DOTATATE and {sup 153}Sm-HA. PC was performed with 3MM/1MM Whatman plates, TCL-Al sheets from Merck and ITLC-SG sheets from Pall Corporation and Varian Inc. The mobile phases were 0.16 mol.L{sup -1} sodium acetate, 0.9% sodium chloride (p/v), 0.1 mol.L{sup -1} sodium citrate buffer, 0.2 mol.L{sup -1} EDTA, methanol:0.4 mol.L{sup -1} ammonium acetate (1:1) mixture, and pyridine:ethanol:water (1:2:4) mixture. The samples were placed on plates in triplicate and immediately put into pre-saturated chambers with the mobile phase. After the chromatographic separation, the plates were dried and cut into 7, 10 or 12 segments and each one was separately measured in a gamma counter during 0.20 minutes (set on the radioisotope window). The results in the gamma counter were expressed in counts per minute (cpm). The chromatographic systems for {sup 177}Lu-DOTATATE and {sup 153}Sm-HA gave the best performances in 0.1 mol L{sup -1} sodium citrate buffer/TLC-Al and 0.9% (p/v) sodium chloride

  11. 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.

  12. Nuclear oncology, a fast growing field of nuclear medicine

    Energy Technology Data Exchange (ETDEWEB)

    Olivier, Pierre E-mail: p.olivier@chu-nancy.fr

    2004-07-11

    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 {sup 111}In-labelled octreotide became a reference imaging method in the detection and staging of neuroendocrine tumors while {sup 131}I- and {sup 123}I-MIBG remain the tracers of reference for pheochromocytomas and neuroblastomas. Lymphoscintigraphic imaging based on peritumoral injection of {sup 99m}Tc-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 {sup 18}F-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 {sup 90}Y-labelled anti-CD20 antibody ({sup 90}Y-ibritumomab tiuxetan (Zevalin{sup [reg]})) approved in US for the treatment of some subtypes of non-Hodgkin's lymphoma. Radionuclide-bone pain palliation has experienced developments with {sup 153}Sm-EDTMP, 186Re-HEDP or {sup 89}Sr, efficient in patients with widespread disease. Last, the same peptides, as those used in SRS, are being developed for therapy, labelled with {sup 90}Y, {sup 111}In or {sup 177}Lu in patients who failed to respond to other treatments. Overall, nuclear oncology is currently a fast growing field thanks to the combined

  13. 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.

  14. 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.

  15. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    OpenAIRE

    Kam, Boen; Teunissen, Jaap; Krenning, Eric; de Herder, Wouter; Khan, Saima; van Vliet, Esther; Kwekkeboom, Dirk Jan

    2012-01-01

    textabstractTreatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with 177Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with 177Lu-[DOTA 0,Tyr3]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with 177Lu-DOTATATE as well as the limi...

  16. Drug: D05795 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available Various pain palliation radiopharmaceuticals V10BX02 Samarium (153Sm) lexidronam D05795 Samarium (153Sm) lex...HERAPEUTIC RADIOPHARMACEUTICALS V10B PAIN PALLIATION (BONE SEEKING AGENTS) V10BX

  17. Theranostic Applications of Lutetium-177 in Radionuclide Therapy.

    Science.gov (United States)

    Das, Tapas; Banerjee, Sharmila

    2016-01-01

    Lutetium-177 has been widely discussed as a radioisotope of choice for targeted radionuclide therapy. The simultaneous emission of imageable gamma photons [208 keV (11%) and 113 keV (6.4%)] along with particulate β(-) emission [β(max) = 497 keV] makes it a theranostically desirable radioisotope. In the present article, the possibility of using two 177Lu-based agents viz. 177Lu-EDTMP and 177Lu-DOTATATE for theranostic applications in metastatic bone pain palliation (MBPP) and peptide receptor radionuclide therapy (PRRT), have been explored. In the case of 177Lu-EDTMP, the whole-body images obtained are compared with those recorded using 99mTc-MDP in the same patient. On the other hand, pre-therapy images acquired with 177Lu-DOTA-TATE are compared with similar images obtained with standard agents, such as 99mTc-HYNIC-TOC (SPECT) and 68Ga-DOTA-TOC (PET) in the same patient. The advantage of the long physical half-life (T1/2) of 177Lu has been utilized in mapping the pharmacokinetics of two additional agents, 177Lu-labeled hydroxyapatite (HA) in radiation synovectomy of knee joints and 177Lu-HA for therapy of hepatocellular carcinoma. Results of these multiple studies conclusively document the potential of 177Lu as a theranostic radioisotope. PMID:25771364

  18. The IEA-R1 research reactor: 50 years of operating experience and utilization for research, teaching and radioisotopes production

    International Nuclear Information System (INIS)

    This paper describes almost 50 years of operating experience and utilization of the IEA-R1 research reactor for research, teaching and radioisotopes production. The current and future program of upgrading the reactor is also described. IEA-R1 research reactor at the Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, Brazil is the largest power research reactor in Brazil, with a maximum power rating of 5 MWth. It is being used for basic and applied research in the nuclear and neutron related sciences, for the production of radioisotopes for medical and industrial applications, and for providing services of neutron activation analysis, real time neutron radiography, and neutron transmutation doping of silicon. IEA-R1 is a swimming pool reactor, with light water as the coolant and moderator, and graphite and beryllium as reflectors. The reactor was commissioned on September 16, 1957 and achieved its first criticality. It is currently operating at 3.5 MWth with a 64-hour cycle per week. In the early sixties, IPEN produced 131I, 32P, 198Au, 24Na, 35S, 51Cr and labeled compounds for medical use. In the year 1980, production of 99mTc generator kits from the fission 99Mo imported from Canada was started. This production is continuously increasing, with the current rate of about 16,000 Ci of 99mTC per year. The 99mTc generator kits, with activities varying from 250 mCi to 2,000 mCi, are distributed to more than 260 hospitals and clinics in Brazil. Several radiopharmaceutical products based on 131I , 32P, 51Cr and 153Sm are also produced. During the past several years, a concerted effort has been made in order to upgrade the reactor power to 5 MWth through refurbishment and modernization programs. One of the reasons for this decision was to produce 99Mo at IPEN. The reactor cycle will be gradually increased to 120 hours per week continuous operation. It is anticipated that these programs will assure the safe and sustainable operation of the IEA-R1 reactor for

  19. Possible use of ignited sulphates as carrier for concentrating some radioactive species (e.g. 51Cr, 99Mo and 185W)

    International Nuclear Information System (INIS)

    A radioactive indicator study has been done to examine the feasibility of concentrating chromate, molybdate and tungstate species from extremely dilute solutions by using ignited lead sulphate and barium sulphate as carriers. The procedure consists of two steps; first, the radioactive tracer in dilute aqueous solution is carried under optimum conditions; secondly, the carried activity after washing can be leached back in minimal amount of water of specified acidity. An examination of working conditions e.g., (i) carrying as a function of pH2, amount of carrier and that of added inactive CrO24; (ii) adsorption/desorption efficiency as a function of lattice/non-lattice ion concn, and (iii) desorption as a function of pH of the eluant have been carried out in case of chromate species. Centrifuge method has been used. 3-4 extractions are needed for the maximum recovery of activity. (author)

  20. Measuring glomerular filtration rate using 51Cr-EDTA: body surface area normalization before or after Bröchner-Mortensen correction?

    OpenAIRE

    Pottel, Hans; Hoste, Liesbeth; De Waele, Liesbeth; Braat, Elke; Baete, Kristof; Goffin, Karolien; Levtchenko, Elena; Gheysens, Olivier

    2014-01-01

    Guidelines for measuring glomerular filtration rate (GFR) using Cr-EDTA require normalizing of GFR for body surface area (BSA) before applying the Bröchner-Mortensen (BM) correction. The guideline explicitly mentions the importance of performing BSA normalization before BM correction and that this is particularly important in children in whom the effects of BSA normalization are largest.

  1. 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

  2. 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

  3. 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

  4. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kam, B.L.R.; Teunissen, J.J.M.; Krenning, E.P.; Khan, S.; Vliet, E.I. van; Kwekkeboom, D.J. [Erasmus MC, Department of Nuclear Medicine, Rotterdam (Netherlands); Herder, W.W. de [Erasmus MC, Department of Internal Medicine, Rotterdam (Netherlands)

    2012-02-15

    Treatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with {sup 177}Lu-labelled somatostatin analogues that have been used for peptide receptor radionuclide therapy (PRRT). The results obtained with {sup 177}Lu-[DOTA{sup 0},Tyr{sup 3}]octreotate (DOTATATE) are very encouraging in terms of tumour regression. Dosimetry studies with {sup 177}Lu-DOTATATE as well as the limited side effects with additional cycles of {sup 177}Lu-DOTATATE suggest that more cycles of {sup 177}Lu-DOTATATE can be safely given. Also, if kidney-protective agents are used, the side effects of this therapy are few and mild and less than those from the use of {sup 90}Y-[DOTA{sup 0},Tyr{sup 3}]octreotide (DOTATOC). Besides objective tumour responses, the median progression-free survival is more than 40 months. The patients' self-assessed quality of life increases significantly after treatment with {sup 177}Lu-DOTATATE. Lastly, compared to historical controls, there is a benefit in overall survival of several years from the time of diagnosis in patients treated with {sup 177}Lu-DOTATATE. These findings compare favourably with the limited number of alternative therapeutic approaches. If more widespread use of PRRT can be guaranteed, such therapy may well become the therapy of first choice in patients with metastasized or inoperable neuroendocrine tumours. (orig.)

  5. Melanoma targeting property of a Lu-177-labeled lactam bridge-cyclized alpha-MSH peptide

    OpenAIRE

    Guo, Haixun; Miao, Yubin

    2013-01-01

    The purpose of this study was to determine the melanoma targeting property of 177Lu-DOTA-GGNle-CycMSHhex in B16/F1 melanoma-bearing C57 mice. 177Lu-DOTA-GGNle-CycMSHhex exhibited high receptor-mediated melanoma uptake and fast urinary clearance. The tumor uptake of 177Lu-DOTA-GGNle-CycMSHhex was 20.25 ± 4.59 and 21.63 ± 6.27% ID/g at 0.5 and 2 h post-injection, respectively. Approximately 83% of injected dose cleared out the body via urinary system at 2 h post-injection. 177Lu-DOTA-GGNle-CycM...

  6. 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

  7. Beta emitters rhenium-188 and lutetium-177 are equally effective in radioimmunotherapy of HPV-positive experimental cervical cancer.

    Science.gov (United States)

    Phaeton, Rebecca; Jiang, Zewei; Revskaya, Ekaterina; Fisher, Darrell R; Goldberg, Gary L; Dadachova, Ekaterina

    2016-01-01

    Cervical cancer caused by the infection with the human papillomavirus (HPV) remains the fourth leading killer of women worldwide. Therefore, more efficacious treatments are needed. We are developing radioimmunotherapy (RIT) of HPV-positive cervical cancers by targeting E6 and E7 viral oncoproteins expressed by the cancer cells with the radiolabeled monoclonal antibodies (mAbs). To investigate the influence of different radionuclides on the RIT efficacy-we performed RIT of experimental cervical cancer with Rhenium-188 ((188) Re) and Lutetium-177 ((177) Lu)-labeled mAb C1P5 to E6. The biodistribution of (188) Re- and (177) Lu-labeled C1P5 was performed in nude female mice bearing CasKi cervical cancer xenografts and the radiation dosimetry calculations for the tumors and organs were carried out. For RIT the mice were treated with 7.4 MBq of either (188) Re-C1P5 or (177) Lu-C1P5 or left untreated, and observed for their tumor size for 28 days. The levels of (188) Re- and (177) Lu-C1P5 mAbs-induced double-strand breaks in CasKi tumors were compared on days 5 and 10 post treatment by staining with anti-gamma H2AX antibody. The radiation doses to the heart and lungs were similar for both (177) Lu-C1P5 and (188) Re-C1P5. The dose to the liver was five times higher for (177) Lu-C1P5. The doses to the tumor were 259 and 181 cGy for (177) Lu-C1P5 and (188) Re-C1P5, respectively. RIT with either (177) Lu-C1P5 or (188) Re-C1P5 was equally effective in inhibiting tumor growth when each was compared to the untreated controls (P = 0.001). On day 5 there was a pronounced staining for gamma H2AX foci in (177) Lu-C1P5 group only and on day 10 it was observed in both (177) Lu-C1P5 and (188) Re-C1P5 groups. (188) Re- and (177) Lu-labeled mAbs were equally effective in arresting the growth of CasKi cervical tumors. Thus, both of these radionuclides are candidates for the clinical trials of this approach in patients with advanced, recurrent or metastatic cervical cancer. PMID:26625938

  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. High purity materials as targets for radioisotope production: Needs and challenges

    Indian Academy of Sciences (India)

    V Shivarudrappa; K V Vimalnath

    2005-07-01

    Radionuclides have become powerful and indispensable tools in many endeavours of human activities, most importantly in medicine, industry, biology and agriculture, apart from R&D activities. Ready availability of radionuclides in suitable radiochemical form, its facile detection and elegant tracer concepts are responsible for their unprecedented use. Application of radioisotopes in medicine has given birth to a new branch, viz. nuclear medicine, wherein radioisotopes are used extensively in the diagnosis and treatment of variety of diseases including cancer. Artificial transmutation of an element employing thermal neutrons in a reactor or high energy particle accelerators (cyclotrons) are the routes of radioisotope production world over. Availability of high purity target materials, natural or enriched, are crucial for any successful radioisotope programme. Selection of stable nuclides in suitable chemical form as targets with desired isotopic and chemical purity are among the important considerations in radioisotope production. Mostly the oxide, carbonate or the metal itself are the preferred target forms for neutron activation in a research reactor. Chemical impurities, particularly from the elements of the same group, put a limitation on the purity of the final radioisotope product. Whereas the isotopic impurities result in the production of undesirable radionuclidic impurities, which affect their effective utilization. Isotope Group, BARC, is in the forefront of radioisotope production and supply in the country, meeting demands for gamut of radioisotope applications indigenously for over four decades now. Radioisotopes such as 131I, 99Mo, 32P, 51Cr, 153Sm, 82Br, 203Hg, 198Au etc are produced in TBq quantities every month and supplied to several users and to Board of Radiation and Isotope Technology (BRIT). Such a large production programme puts a huge demand on the reliable sources of availability of high purity target materials which are at present mostly met

  10. Production and Clinical Applications of Radiopharmaceuticals and Medical Radioisotopes in Iran.

    Science.gov (United States)

    Jalilian, Amir Reza; Beiki, Davood; Hassanzadeh-Rad, Arman; Eftekhari, Arash; Geramifar, Parham; Eftekhari, Mohammad

    2016-07-01

    -meta-iodobenzylguanidine for treatment of neuroblastoma, pheochromocytoma, and other neuroendocrine tumors has been steadily increasing in major academic university hospitals. Also (153)Sm-EDTMP, (177)Lu-EDTMP, (90)Y-citrate, (90)Y-hydroxyapatite colloid, (188/186)Re-sulfur colloid, and (188/186)Re-HEDP have been locally developed and now routinely available for bone pain palliation and radiosynovectomy. Cu-64 has been available to the nuclear medicine community for some time. With recent reports in diagnostic and therapeutic applications of this agent especially in the field of oncology, we anticipate an expansion in production and availability. The initiation of the production line for gallium-68 generator is one of the latest exciting developments. We are proud that Iran would be joining the club of few nations with production lines for this type of generator. There are also quite a number of SPECT and PET tracers at research and preclinical stage of development preliminarily introduced for possible future clinical applications. Availability of fluorine-18 tracers and gallium-68 generators would no doubt allow rapid dissemination of PET/CT practices in various parts of our large country even far from a cyclotron facility. Also, local production and availability of therapeutic radiopharmaceuticals are going to open exciting horizons in the field of nuclear medicine therapy. Given the available manpower, local infrastructure of SPECT imaging, and rapidly growing population, the production of Tc-99m generators and cold kit would continue to flourish in Iran. PMID:27237443

  11. 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.

  12. 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. PMID:27237437

  13. Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications

    International Nuclear Information System (INIS)

    In this work, a potential therapeutic DNA targeting agent, 153Sm-bleomycin complex (153Sm-BLM), was developed and the tumor accumulation studies were performed using single photon emission computed tomography (SPECT) and scarification studies. 153Sm-BLM was prepared at optimized conditions (room temperature, 4-8 h, 0.1 mg bleomycin for 740-3700 MBq 153SmCl3, radiochemical purity over 98%, HPLC, specific activity = 55 TBq/mmol). 153Sm-BLM was administered into human breast cancer murine xenografts and the biodistribution and imaging studies were performed up to 48 h. 153Sm-BLM demonstrated superior tumor accumulation properties in contrast with the other radiolabeled bleomycins with tumor:blood ratios of 41, 72 and 182 at 4, 24 and 48 h, respectively, and tumor:muscle ratios of 23, 33 and > 1490 at 4, 24 and 48 h, respectively, while administered intravenously. The SPECT images also demonstrated the obvious tumor uptake at the chest region of the breast-tumor bearing mice. These initial experiments demonstrate significant accumulation of 153Sm-BLM in tumor tissues. (orig.)

  14. Bioaccumulation studies in a benthic marine species in different radioactivity concentrations

    International Nuclear Information System (INIS)

    The accumulation of trivalent and hexavalent 51Cr by the mollusc Venus verrucosa in three different radioactivity concentrations was studied. The bioavailability of the trivalent 51Cr was found to be much higher than that of the hexavalent 51Cr. Also the uptake patterns of 51Cr(III) and 51Cr(VI) were different. This distribution of the accumulated trivalent and hexavalent 51Cr in the body of Venus verrucosa was investigated and appeared to be influenced by the valence state of 51Cr. The elimination of the accumulated radioactivity was also investigated and the effective and biological half lives for the two year valence states of 51Cr were determined

  15. 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

  16. Production and evaluation of Lutetium-177 maltolate as a possible therapeutic agent

    International Nuclear Information System (INIS)

    Development of oral therapeutic radiopharmaceuticals is a new concept in radiopharmacy. Due to the interesting therapeutic properties of 177Lu and oral bioavailability of maltolate (MAL) metal complexes, 177Lu-maltolate (177Lu-MAL) was developed as a possible therapeutic compound for ultimate oral administration. The specific activity of 2.6-3 GBq/mg was obtained by irradiation of natural Lu2O3 sample with thermal neutron flux of 4x1013 n.cm-2.s-1 for Lu-177. The product was converted into chloride form which was further used for labeling maltol (MAL). At optimized conditions a radiochemical purity of about >99% was obtained for 177Lu-MAL shown by ITLC (specific activity, 970-1000 Mbq/mmole). The stability of the labeled compound as well as the partition coefficient was determined in the final solution up to 24h. Biodistribution studies of Lu-177 chloride and 177Lu-MAL were carried out in wild-type rats for post-oral distribution phase data. Lu-MAL is a possible therapeutic agent in human malignancies for the bone palliation therapy so the efficacy of the compound should be tested in various animal models.

  17. Electron microscopic observations and DNA chain fragmentation studies on apoptosis in bone tumor cells induced by 153Sm—EDTMP

    Institute of Scientific and Technical Information of China (English)

    ZhuShou-Peng; XiaoDong; 等

    1997-01-01

    The morphological changes observed by electron microscopy indicate that after internal irradiation with 153Sm-ESTMP bone tumor cells displayed feature of apoptosis,such as margination of condensed chromatin,chromatin fragmentation.as well as the membranebouded apoptotic bodies formation.THe quantification analysis of fragmentation DNA for bone tumor cells induced by 153Sm-EDTMP shows that the DNA fragmentation is enhanced with the prolongation of internally irradiated time.These characteristics suggest that 153Sm-EDTMP internal irradiation could induce bone tumor cells to go9 to apoptosis.

  18. 177Lu-OPS201 targeting somatostatin receptors

    DEFF Research Database (Denmark)

    Beykan, Seval; Dam, Jan S; Eberlein, Uta;

    2016-01-01

    kidneys (13.7 Gy), the osteogenic cells (3.9 Gy), the urinary bladder wall (1.8 Gy), and the liver (1.0 Gy). No metabolites of (177)Lu-OPS201 were found by radio HPLC analysis. None of the absorbed doses calculated will exceed organ toxicity levels. CONCLUSIONS: The (177)Lu-OPS201 was well tolerated and......-integrated activity coefficients were calculated for the organs showing visible uptake. Based on these data, the absorbed organ dose coefficients for a 70-kg patient were calculated with OLINDA/EXM. For humans after an injection of 5 GBq (177)Lu-OPS201, the highest predicted absorbed doses are obtained for the...

  19. 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.)

  20. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    International Nuclear Information System (INIS)

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG4-BN(7-14) (DOTA-PESIN), with the goal of labelling it with 67/68Ga and 177Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG4). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [GaIII/LuIII]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [67Ga/177Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [67Ga/177Lu]-DOTA-PESIN. [67Ga/177Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [68Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the 177Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with 68/67Ga and targeted radionuclide therapy with 177Lu. (orig.)

  1. Optimization of hydroxyapatite particles labeling with samarium-153 as a therapeutic agent for radiation synovectomy

    Energy Technology Data Exchange (ETDEWEB)

    Aungurarat, Angkanan [Isotope Production Division, Office of Atomic Energy for Peace, Vibhawadi Rangsit, Chatuchak, Bangkok (Thailand)

    2000-10-01

    Hydroxyapatite (HA) was studied as a particulate carrier for beta-emitting radionuclides in radiation synovectomy. Particles were labeled with {sup 153}Sm (T{sub 1/2}=1.95 days, {beta}-energy=810 (20%), 710 (50%), 640 (30%) keV, {gamma}-energy=103.2 (29.8%) keV, range of beta particles in tissue is 2.5 mm). Labeling efficiency was greater than 95% at pH 4-6. The compounds is sterile and pyrogen free with its stability of 6 days. In vivo studies by intra-articular injection into the knee joints of normal rats showed the total cumulative leakage of {sup 153} Sm over 6 days was around 2 percentage injected dose (ID). The ease of preparation of {sup 153}Sm-HA, the high efficiency of labeling and low leakage from the joint make {sup 153}Sm-HA attractive for radiation synovectomy. (author)

  2. 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

  3. 放射性核素标记的新型生长抑素类似物肿瘤诊疗进展

    Institute of Scientific and Technical Information of China (English)

    王松; 包铮; 梁庆模

    2011-01-01

    @@ 放射性核素标记的生长抑素类似物(somatostatin analog,SSTA)常见的有(111)In-奥曲肽(Octreo Scan),(90)Y-奥曲肽(90)Y-DOTATOC,(177)Lu-奥曲肽(177)Lu-DOTATATE)等(图1),三者对生长抑素受体(somatostatin receptor,SSTR) 2均具有较强的亲和力,肿瘤摄取量高,并已进人临床研究阶段.

  4. Lutetium-177-EDTMP for pain palliation in bone metastases

    International Nuclear Information System (INIS)

    Experiences with the new palliative agent Lu-177 EDTMP are summarized. The production of primary 177Lu by the 176Lu(n,γ) 177Lu reaction and the synthesis of the radioactive complex are described as well as the procedures used for the control of the radionuclidic and the radiochemical purity. The stability of the compound has been also studied. The in vivo essays with rats and the use of the radiopharmaceutical, after a careful dose evaluation, in a patient with bone metastases from a breast cancer, show that the behaviour of Lu-177 EDTMP is similar to that of the analogue Sm-153 EDTMP. (author)

  5. Determination of peptide content of DOTA-peptides by metal titration and UPLC

    International Nuclear Information System (INIS)

    Radiolabelled DOTA-peptides are in use for Peptide Receptor Radionuclide Scintigraphy (PRS) and Therapy (PRRT), e.g with 177Lu-DOTA-TATE or 90Y-DOTATOC. Labelling conditions are frequently critical. Therefore, the ingredients of the reaction, e.g. radiometal (90Y and 177Lu) and DOTA-peptide should be pure and the content known. Quality control of DOTA-peptide, can be performed with various methods, most commonly by UV. There are numerous conditions in which this is hampered, e.g. impurities may also have UV-absorption. The aim of the study was to quantify content and purity of DOTA-peptide

  6. 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...

  7. Preparation and examination of properties of samarium-153-EDTMP complex; Otrzymywanie chelatu kwasu etylenodiaminotetrametylenofosfonowego (EDTMP) z samarem-153 i badanie jego wlasciwosci

    Energy Technology Data Exchange (ETDEWEB)

    Nowak, M. [Institute of Atomic Energy, Otwock-Swierk (Poland); Garnuszek, P.; Lukasiewicz, A.; Wozniak, I.; Zulczyk, W. [Osrodek Badawczo-Rozwojowy Izotopow, Otwock-Swierk (Poland); Licinska, I. [Instytut Lekow, Warsaw (Poland)

    1995-12-31

    Preparation and properties of ethylenediaminetetramethylenephosphonic acid (EDTMP) as well as some properties of {sup 153}Sm-EDTMP chelate have been examined. The chelate formed by samarium-153 (46.3 h, {beta}{sup -}-decay) with EDTMP exhibits high bone uptake and can be used for treatment of disseminated, painful skeletal metastases. The purity and stability of solutions of {sup 153}Sm-EDTMP chelate were examined in a broad range of samarium concentration and {sup 153}Sm specific activity. The complex under study was examined by radio-TLC, -electrophoresis and radio-HPLC. The results obtained suggest the small size of molecules of {sup 153}Sm-EDTMP chelate as compared with molecules of ``free``EDTMP. The results of biodistribution of {sup 153}Sm-EDTMP determined in rats indicate the quick blood clearance, high deposition of radioactivity in bone and quick excretion of radioactivity into urine. No specific uptake of {sup 153}Sm-EDTMP in extra-skeletal organs was found. (author). 42 refs, 13 figs, 22 tabs.

  8. Effects of increasing doses of samarium-153-ethylenediaminetetramethylene phosphonate on axial and appendicular skeletal growth in juvenile rabbits

    International Nuclear Information System (INIS)

    Introduction: Targeted radiotherapy using samarium-153-ethylenediaminetetramethylene phosphonate (153Sm-EDTMP) is currently under investigation for treatment of osteosarcoma. Osteosarcoma often occurs in children, and previous studies on a juvenile rabbit model demonstrated that clinically significant damage to developing physeal cartilage may occur as a result of systemic 153Sm-EDTMP therapy. The aim of this study was to evaluate the late effects of 153Sm-EDTMP on skeletal structures during growth to maturity and to determine if there is a dose response of 153Sm-EDTMP on growth of long bones. Methods: Female 8-week-old New Zealand white rabbits were divided into three treatment groups plus controls. Each rabbit was intravenously administered a predetermined dose of 153Sm-EDTMP. Multiple bones of each rabbit were radiographed every 2 months until physeal closure, with subsequent measurements made to assess for abbreviated bone growth. Statistical analyses were performed to determine the differences in bone length between groups, with significance set at P153Sm-EDTMP. Further investigation regarding the effects of bone-seeking radiopharmaceuticals on bone growth and physeal cartilage is warranted

  9. 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

  10. The Level of Europium-154 Contaminating Samarium-153-EDTMP Activates the Radiation Alarm System at the US Homeland Security Checkpoints

    Directory of Open Access Journals (Sweden)

    Mohammed Najeeb Al Hallak

    2009-08-01

    Full Text Available 153Sm-EDTMP is a radiopharmaceutical composed of EDTMP (ethylenediamine-tetramethylenephosphonate and Samarium-153 [1]. 153Sm-EDTMP has an affinity for skeletal tissue and concentrates in areas with increased bone turnover; thus, it is successfully used in relieving pain related to diffuse bone metastases [1]. The manufacturing process of 153Sm-EDTMP leads to contamination with 154Eu (Europium-154 [2]. A previous study only alluded to the retention of 154Eu in the bones after receiving treatment with 153Sm-EDTMP [2]. Activation of the alarm at security checkpoints after 153Sm-EDTMP therapy has not been previously reported. Two out of 15 patients who received 153Sm-EDTMP at Roger Maris Cancer Center (Fargo, N. Dak., USA activated the radiation activity sensors while passing through checkpoints; one at a US airport and the other while crossing theAmerican-Canadian border. We assume that the 154Eu which remained in the patients’ bones activated the sensors. Methods: In order to investigate this hypothesis, we obtained the consent from 3 of our 15 patients who received 153Sm-EDTMP within the previous 4 months to 2 years, including the patient who had activated the radiation alarm at the airport. The patients were scanned with a handheld detector and a gamma camera for energies from 511 keV to 1.3 MeV. Results: All three patients exhibited identical spectral images, and further analysis showed that the observed spectra are the result of 154Eu emissions. Conclusion: Depending on the detection thresholds and windows used by local and federal authorities, the remaining activity of 154Eu retained in patients who received 153Sm-EDTMP could be sufficient enough to increase the count rates above background levels and activate the sensors. At Roger Maris Cancer Center, patients are now informed of the potential consequences of 153Sm-EDTMP therapy prior to initiating treatment. In addition, patients treated with 153Sm-EDTMP at Roger Maris Cancer Center

  11. Lutetium-labelled peptides for therapy of neuroendocrine tumours

    NARCIS (Netherlands)

    B.L. Kam (Boen); J.J.M. Teunissen (Jaap); E.P. Krenning (Eric); W.W. de Herder (Wouter); S. Khan (Saima); E.I. van Vliet (Esther); D.J. Kwekkeboom (Dirk Jan)

    2012-01-01

    textabstractTreatment with radiolabelled somatostatin analogues is a promising new tool in the management of patients with inoperable or metastasized neuroendocrine tumours. Symptomatic improvement may occur with 177Lu-labelled somatostatin analogues that have been used for peptide receptor radionuc

  12. Optimizing lutetium 177-anti-carbonic anhydrase IX radioimmunotherapy in an intraperitoneal clear cell renal cell carcinoma xenograft model

    NARCIS (Netherlands)

    Muselaers, C.H.J.; Oosterwijk, E.; Bos, D.L.; Oyen, W.J.G.; Mulders, P.F.A.; Boerman, O.C.

    2014-01-01

    A new approach in the treatment of clear cell renal carcinoma (ccRCC) is radioimmunotherapy (RIT) using anti-carbonic anhydrase IX (CAIX) antibody G250. To investigate the potential of RIT with lutetium 177 (177Lu)-labeled G250, we conducted a protein dose escalation study and subsequently an RIT st

  13. Activity estimation in radioimmunotherapy using magnetic nanoparticles

    Science.gov (United States)

    Rajabi, Hossein; Johari Daha, Fariba

    2015-01-01

    Objective Estimation of activity accumulated in tumor and organs is very important in predicting the response of radiopharmaceuticals treatment. In this study, we synthesized 177Lutetium (177Lu)-trastuzumab-iron oxide nanoparticles as a double radiopharmaceutical agent for treatment and better estimation of organ activity in a new way by magnetic resonance imaging (MRI). Methods 177Lu-trastuzumab-iron oxide nanoparticles were synthesized and all the quality control tests such as labeling yield, nanoparticle size determination, stability in buffer and blood serum up to 4 d, immunoreactivity and biodistribution in normal mice were determined. In mice bearing breast tumor, liver and tumor activities were calculated with three methods: single photon emission computed tomography (SPECT), MRI and organ extraction, which were compared with each other. Results The good results of quality control tests (labeling yield: 61%±2%, mean nanoparticle hydrodynamic size: 41±15 nm, stability in buffer: 86%±5%, stability in blood serum: 80%±3%, immunoreactivity: 80%±2%) indicated that 177Lu-trastuzumab-iron oxide nanoparticles could be used as a double radiopharmaceutical agent in mice bearing tumor. Results showed that 177Lu-trastuzumab-iron oxide nanoparticles with MRI had the ability to measure organ activities more accurate than SPECT. Conclusions Co-conjugating radiopharmaceutical to MRI contrast agents such as iron oxide nanoparticles may be a good way for better dosimetry in nuclear medicine treatment. PMID:25937783

  14. 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...

  15. 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

  16. Successful radiopeptide targeting of metastatic anaplastic meningioma: Case report

    Directory of Open Access Journals (Sweden)

    Biersack Hans-Jürgen

    2011-08-01

    Full Text Available Abstract A patient with anaplastic meningioma and lung metastases resistant to conventional treatment underwent radiopeptide therapy with 177Lu- DOTA-octreotate in our institute. The treatment resulted in significant improvement in patient's quality of life and inhibition of tumor progression. This case may eventually help to establish the value of radiopeptide therapy in patients with this rare condition.

  17. Biokinetics and dosimetry of several radiolabelled peptides in cancer cells

    Science.gov (United States)

    Rodríguez-Cortés, J.; Ferro-Flores, G.; de Murphy, C. Arteaga; Pedraza-López, M.; Ramírez-Iglesias, M. A. T.

    Radiolabelled peptides have been used as target-specific radiopharmaceuticals. The goal of this research was the in vitro assessment of the uptake, internalization, externalization, and efflux of five radiolabelled peptides in cancer cells to estimate radiation-absorbed doses from experimental biokinetic data. 177Lu-DOTA-octreotate, 188Re-lanreotide, and 99mTc-HYNIC-octreotide were studied in the AR42J cell line. The PC3 and NCIH69 cells were used for 99mTc-HYNIC-bombesin and 177Lu-DOTA-minigastrin, respectively. The cumulated activities in the membrane and cytoplasm were calculated by integration of the experimental time-activity curves and used for dosimetry calculations according to the Medical Internal Radiation Dose (MIRD) cellular methodology. The mean absorbed dose to the cell nucleus were 0.69±0.09, 0.11±0.08, 0.55±0.09, 3.45±0.48, and 3.30±0.65 Gy/Bq for 99mTc-HYNIC-bombesin, 99mTc-HYNIC-octreotide, 177Lu-DOTA-minigastrin, 177Lu-DOTA-octreotate, and 188Re-lanreotide, respectively. If radiopharmaceutical cell kinetics were not used and only uptake data were considered, the calculated doses would be overestimated up to 25 times.

  18. Evaluation and application of the low energy electron emitter 161Tb

    International Nuclear Information System (INIS)

    The low energy electron emitter 161Tb was produced n.c.a. in quantities sufficient for therapeutic applications and successfully used for labeling of peptides and antibodies. Furthermore, these compounds have been compared to n.c.a. 177Lu labeled mAbs via cell experiments, a radionuclide that is already used in clinical nuclear oncology.

  19. 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

  20. 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

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

    International Nuclear Information System (INIS)

    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 111In, 90Y, or 177Lu-labelled somatostatin analogues that have been used. Since tumour size reduction was seldom achieved with 111Indium labelled somatostatin analogues, radiolabelled somatostatin analogues with beta-emitting isotopes like 90Y and 177Lu were developed. Reported anti-tumour effects of [90Y-DOTA0,Tyr3]octreotide vary considerably between various studies: Tumour regression of 50% or more was achieved in 9 to 33% (mean 22%). With [177Lu-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 [90Y-DOTA0,Tyr3]octreotide and [177Lu-DOTA0,Tyr3]octreotate is 30 months and more than 36 months respectively. Lastly, quality of life improves significantly after treatment with [177Lu-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-radioiodine-avid differentiated thyroid carcinoma might become more important

  2. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer

    International Nuclear Information System (INIS)

    Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with β- emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH2. The use of SP labeled with different radionuclides including 177Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with 177Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of 17Lu -DOTA- SP radiolabeled with low activity of 177Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of 177Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with 177Lu-DOTA-SP, radiolabeled in the absence and presence of

  3. Lutetium-177 Labeled Bombesin Peptides for Radionuclide Therapy.

    Science.gov (United States)

    Reynolds, Tamila Stott; Bandari, Rajendra P; Jiang, Zongrun; Smith, Charles J

    2016-01-01

    The rare-earth radionuclides that decay by beta particle (β-) emission are considered to be ideal in the context of targeted radiotherapy. The rare-earth isotopes exist primarily in the 3+ oxidation state and are considered to be hard metal centers, requiring multidentate, hard donor ligands such as the poly(aminocarboxylates) for in vivo kinetic inertness. 177Lu is a rare-earth radionuclide that is produced in moderate specific activity (740 GBq/mg) by direct neutron capture of enriched 176Lu via the 176Lu(n,γ)177Lu nuclear reaction. 177Lu has a half-life of 6.71 d, decays by beta emission (Ebmax = 0.497 MeV), and emits two imagable photons (113keV, 3% and 208kev, 11%). High specific activity, no-carrier-added 177Lu can also be prepared by an indirect neutron capture nuclear reaction on a 176Yb target. Herein, we report upon bombesin (BBN) peptides radiolabeled with 177Lu. The impetus driving many of the research studies that we have described in this review is that the high-affinity gastrin releasing peptide receptor (GRPR, BBN receptor subtype 2, BB2) has been identified in tissue biopsy samples and immortalized cell lines of many human cancers and is an ideal biomarker for targeting early-stage disease. Early on, the ability of GRPR agonists to be rapidly internalized coupled with a high incidence of GRPR expression on various neoplasias was a driving force for the design and development of new diagnostic and therapeutic agents targeting GRP receptor-positive tumors. Recent reports, however, show compelling evidence that radiopharmaceutical design and development based upon antagonist-type ligand frameworks clearly bears reexamination. Last of all, the ability to target multiple biomarkers simultaneously via a heterodimeric targeting ligand has also provided a new avenue to investigate the dual targeting capacity of bivalent radioligands for improved in vivo molecular imaging and treatment of specific human cancers. In this report, we describe recent advances

  4. 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.

  5. DOTA-PESIN, a DOTA-conjugated bombesin derivative designed for the imaging and targeted radionuclide treatment of bombesin receptor-positive tumours

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Hanwen; Maecke, Helmut R. [University Hospital Basel, Division of Radiological Chemistry, Department of Radiology, Basel (Switzerland); Schuhmacher, Jochen; Eisenhut, Michael [German Cancer Research Centre, Department of Radiopharmaceutical Chemistry, Heidelberg (Germany); Waser, Beatrice; Reubi, Jean Claude [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Berne (Switzerland); Wild, Damian [University Hospital, Clinic and Institute of Nuclear Medicine, Department of Radiology, Basel (Switzerland)

    2007-08-15

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG{sub 4}-BN(7-14) (DOTA-PESIN), with the goal of labelling it with {sup 67/68}Ga and {sup 177}Lu for diagnosis and radionuclide therapy of prostate and other human cancers overexpressing bombesin receptors. The 8-amino acid peptide bombesin (7-14) was coupled to the macrocyclic chelator DOTA via the spacer 15-amino-4,7,10,13-tetraoxapentadecanoic acid (PEG{sub 4}). The conjugate was complexed with Ga(III) and Lu(III) salts. The GRP receptor affinity and the bombesin receptor subtype profile were determined in human tumour specimens expressing the three bombesin receptor subtypes. Internalisation and efflux studies were performed with the human GRP receptor cell line PC-3. Xenografted nude mice were used for biodistribution. [Ga{sup III}/Lu{sup III}]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN internalised rapidly into PC-3 cells whereas the efflux from PC-3 cells was relatively slow. In vivo experiments showed a high and specific tumour uptake and good retention of [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN. [{sup 67}Ga/{sup 177}Lu]-DOTA-PESIN highly accumulated in GRP receptor-expressing mouse pancreas. The uptake specificity was demonstrated by blocking tumour uptake and pancreas uptake. Fast clearance was found from blood and all non-target organs except the kidneys. High tumour-to-normal tissue ratios were achieved, which increased with time. PET imaging with [{sup 68}Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the {sup 177}Lu-labelled peptide remained in the tumour even 3 days post injection. The newly designed ligands have high potential with regard to PET and SPECT imaging with {sup 68/67}Ga and targeted radionuclide therapy with {sup 177}Lu. (orig.)

  6. Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities

    Science.gov (United States)

    Hashikin, Nurul Ab. Aziz; Yeong, Chai-Hong; Abdullah, Basri Johan Jeet; Ng, Kwan-Hoong; Chung, Lip-Yong; Dahalan, Rehir; Perkins, Alan Christopher

    2015-01-01

    Introduction Samarium-153 (153Sm) styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y) microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy. Methods The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620–830 μm), which were reduced to 20–40 μm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,γ)153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 1012 n.cm-2.s-1 neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g-1. Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles. Results Fourier Transform Infrared (FTIR) spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%. Conclusion The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization. PMID:26382059

  7. Neutron Activated Samarium-153 Microparticles for Transarterial Radioembolization of Liver Tumour with Post-Procedure Imaging Capabilities.

    Directory of Open Access Journals (Sweden)

    Nurul Ab Aziz Hashikin

    Full Text Available Samarium-153 (153Sm styrene divinylbenzene microparticles were developed as a surrogate for Yttrium-90 (90Y microspheres in liver radioembolization therapy. Unlike the pure beta emitter 90Y, 153Sm possess both therapeutic beta and diagnostic gamma radiations, making it possible for post-procedure imaging following therapy.The microparticles were prepared using commercially available cation exchange resin, Amberlite IR-120 H+ (620-830 μm, which were reduced to 20-40 μm via ball mill grinding and sieve separation. The microparticles were labelled with 152Sm via ion exchange process with 152SmCl3, prior to neutron activation to produce radioactive 153Sm through 152Sm(n,γ153Sm reaction. Therapeutic activity of 3 GBq was referred based on the recommended activity used in 90Y-microspheres therapy. The samples were irradiated in 1.494 x 10(12 n.cm(-2.s(-1 neutron flux for 6 h to achieve the nominal activity of 3.1 GBq.g(-1. Physicochemical characterisation of the microparticles, gamma spectrometry, and in vitro radiolabelling studies were carried out to study the performance and stability of the microparticles.Fourier Transform Infrared (FTIR spectroscopy of the Amberlite IR-120 resins showed unaffected functional groups, following size reduction of the beads. However, as shown by the electron microscope, the microparticles were irregular in shape. The radioactivity achieved after 6 h neutron activation was 3.104 ± 0.029 GBq. The specific activity per microparticle was 53.855 ± 0.503 Bq. Gamma spectrometry and elemental analysis showed no radioactive impurities in the samples. Radiolabelling efficiencies of 153Sm-Amberlite in distilled water and blood plasma over 48 h were excellent and higher than 95%.The laboratory work revealed that the 153Sm-Amberlite microparticles demonstrated superior characteristics for potential use in hepatic radioembolization.

  8. Improving radionuclide therapy in prostate cancer patients with metastatic bone pain

    OpenAIRE

    Lam, M. G. E. H.

    2009-01-01

    Bone seeking radiopharmaceuticals are indicated in cancer patients with multiple painful skeletal metastases. The majority of these patients are hormone-refractory prostate cancer patients in an advanced stage of their disease. Bone seeking radiopharmaceuticals relieve pain and improve the patients quality of life. The mostly used radiopharmaceuticals are 89SrCl2 (Metastron), 153Sm-EDTMP (Quadramet) and 186Re-HEDP. Differences between 89SrCl2, 153Sm-EDTMP and 186Re-HEDP were investigated. It ...

  9. Studies of the radiolabeling and biodistribution of substance P using lutetium-177 as a radiotracer; Estudo da marcacao e biodistribuicao da substancia P utilizando lutecio-177 como radiotracador

    Energy Technology Data Exchange (ETDEWEB)

    Lima, Clarice Maria de

    2011-07-01

    Malignant gliomas are primary brain tumors, resistant to various treatments, as chemotherapy, radiotherapy, induction of apoptosis and surgery. An alternative for the treatment of malignant gliomas is the radionuclide therapy. This technique apply radiolabeled molecules that selectively bind to tumor cells producing cytotoxic effect by dose irradiation, and resulting in death of tumor cells. Most protocols for radionuclide therapy of malignant brain tumors involve the administration of peptides labeled with {beta}{sup -} emitting radioisotopes. The Substance P (SP) is an 11- amino acid neuropeptide, characterized by the C-terminal sequence Phe-X-Gly-Leu-Met-NH{sub 2}. The use of SP labeled with different radionuclides including {sup 177}Lu, have been proposed for in vivo treatment of tumors. SP is the most important target of neurokinin 1 receptors, over expressed in malignant gliomas. The objective of this work was to study conditions of radiolabeling DOTA-SP with {sup 177}Lu, the stability of labeled compound and in vivo and in vitro, to develop a protocol production and evaluate the potential of the radiopharmaceutical in the therapy of gliomas. The labeling conditions were optimized varying the temperature, reaction time, activity of lutetium-177 chloride and mass of DOTA-SP. The radiochemical purity of preparations were analyzed by chromatographic techniques. The stability of {sup 17L}u -DOTA- SP radiolabeled with low activity of {sup 177}Lu was evaluated for different time at 2-8 degree C or incubated in human serum. The stability of the labeled with high activity of {sup 177}Lu was also analyzed in the presence of gentisic acid (6 mg / mL) added after the labeling reaction. The labeled conditions in low and high activity were subjected to evaluation for the ability to cause oxidation of methionine residue, adding the D-L- methionine amino acid to the reaction medium (6 mg / mL) and subsequent chromatographic evaluation. In vitro study with {sup 177}Lu

  10. Current status and future perspectives of PSMA-targeted therapy in Europe: opportunity knocks

    International Nuclear Information System (INIS)

    177Lu-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 177Lu-PSMA-targeted compounds.

  11. Peptide receptor radionuclide therapy with lutetium-177 DOTATATE in a case of recurrent extradrenal retroperitoneal malignant paraganglioma with nodal and bone metastasis

    OpenAIRE

    Koramadai Karuppusamy Kamaleshwaran; Paulvannan Subramaniam; Sudhakar Natarajan; Pavanasam Velayutham; Vyshak Mohanan; Ajit Sugunan Shinto

    2015-01-01

    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 unresectab...

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

    OpenAIRE

    Alireza Aslani; Graeme Snowdon; Dale Bailey; Geoffrey Schembri; Elizabeth Bailey; Pavlakis Nick; Paul Roach

    2015-01-01

    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 syn...

  13. Influence of the amount of co-infused amino acids on post-therapeutic potassium levels in peptide receptor radionuclide therapy

    OpenAIRE

    Werner, Rudolf A; Lapa, Constantin; Bluemel, Christina; Lückerath, Katharina; Schirbel, Andreas; Strate, Alexander; Buck, Andreas K.; Herrmann, Ken

    2014-01-01

    Background Peptide receptor radionuclide therapy (PRRT) is routinely used for advanced or metastasized neuroendocrine tumours (NET). To prevent nephrotoxicity, positively charged amino acids (AA) are co-infused. The aim of this study was to correlate the risk for therapy-related hyperkalaemia with the total amount of AA infused. Methods Twenty-two patients undergoing PRRT with standard activities of 177Lu-DOTATATE/-TOC were monitored during two following treatment cycles with co-i...

  14. EANM'13 - Annual Congress of the European Association of Nuclear Medicine - Selection of abstracts

    International Nuclear Information System (INIS)

    This document gathers the abstracts of the session 'Radionuclide therapy and dosimetry'. The use and performance in therapy and imaging applications of radionuclides such as 188Re, 90Y, 131I, 177Lu, 111In, 124I, 99mTc are presented. Generally the results are based on either studies of small groups of patients at the scale of a hospital or trials on small animals

  15. 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.).

  16. Radiolabeling of substance P with Lutetium-177 and biodistribution study in AR42J pancreatic tumor xenografted Nude mice

    International Nuclear Information System (INIS)

    Pancreatic tumor (PT) is a neuroendocrine neoplasm that usually origin metastases in the respiratory and gastrointestinal tract. In recent years, new developments in targeted therapies have emerged and the presence of peptide receptors at the cell membrane of PT constitutes the basis of the clinical use of specific radiolabeled ligands. Substance P, an 11-amino acid peptide which has an important role in modulating pain transmission trough neurokinin 1 and 2 receptors (NKr), may play a role in the pathogenesis of PT, because approximately 10% of these tumors over express NKr. The aim of the present work was to produce a pure and stable SP analog (DOTA-SP) radiolabeled with Lutetium-177 (177Lu), and to evaluate its in vivo target to AR42J pancreatic tumor cells in Nude mice in other to verify if SP can be used in this pancreatic tumor detection and treatment. 177Lu (half-life 6.7 days) has both β and γ-emissions suitable for radiotherapy and imaging respectively. Substance P was successfully labeled with high yield (>99%) at optimized conditions and kept stable for more than 72 hours at 4 deg C and 24 hours in human plasma. Biodistribution studies showed that SP excretion was mainly performed by renal pathway. In addition, 177Lu-DOTA-SP showed higher uptake by tumor than normal pancreas, indicating the presence of NK receptors in AR42J pancreatic tumor. (author)

  17. Passage of chromium-mordanted and rare earth-labeled fiber: time of dosing kinetics

    International Nuclear Information System (INIS)

    Coastal bermudagrass hay was labeled with Cr by the Cr-mordant procedure and with 177Lu applied to the same fiber. Neutral detergent fiber prepared from the same Coastal bermudagrass hay was labeled with Yb, 169Yb, Tb and 160Tb by soaking overnight following by thorough washing and drying. Wood chips were similarly labeled with Sm or La, and Solka Floc was labeled with 147Nd and 141Ce. The carriers, labels and times of administration to cattle were: bermudagrass fiber with both Cr and 177Lu, bermudagrass fiber with 169Yb and Solka Floc labeled with 147Nd at 0 h; bermudagrass fiber with Yb, Solka Floc with 141Ce and wood chips with Sm at 24 h; wood chips with La at 48 h; and bermudagrass fiber labeled with 160Tb at the beginning and labeled with Tb at the end of a meal. Fecal collection followed and passage characteristics were determined with a two-compartment, age-dependent model. Markers labeling the different fiber sources had different (P less than .01) passage rates (Solka Floc greater than Coastal bermudagrass greater than wood chips), but there was no difference within fiber source for rare earth passage. There also was no difference between the passage characteristics of Cr-mordant and 177Lu. However, passage rate of particles administered at the beginning of the meal (160Tb) was 42% higher than for particles at the end of the meal (Tb)

  18. In vitro Evaluation of a Bombesin Antagonistic Analogue Conjugated with DOTA-Ala(SO{sub 3}H)-Aminooctanoyl for Targeting of the Gastrin-releasing Peptide Receptor

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Lee, So Young; Choi, Sang Mu [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2014-05-15

    As Bombesin (BBS) binds with high affinity to GRPR, BBS derivatives have been labeled with various radionuclides such as {sup 99}mTc, {sup 111}In, {sup 90}Y, {sup 64}Cu, {sup 177}Lu, {sup 68}Ga, or {sup 18}F and have proved to be successful candidates for peptide receptor radiotherapy (PRRT). In this study, we employed Ala(SO{sub 3}H)-Aminooctanoyl as a linker of BBS antagonistic peptide sequence, Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH{sub 2}, with DOTA to prepare radiolabeled candidates for GRPR targeting. A DOTA-conjugated BBS antagonistic analogue was synthesized and radiolabeled with {sup 177}Lu, and in vitro characteristics on GRPR-overexpressing human prostate tumor cells were evaluated. In conclusion, a novel BBS antagonistic analogue, {sup 177}Lu-DOTA-sBBNA, is a promising candidate for the targeting of GRPR-over-expressing tumors. Further investigations to evaluate its in vivo characteristics and therapeutic efficacy are needed.

  19. Studies on the preparation of ferric-hydroxide macro aggregate and hydroxyapatite particles labelled with Sm-153, Ho-166 and/or Dy-165 for radiation synovectomy

    International Nuclear Information System (INIS)

    The modified methods for the preparation of Hydroxyapatite particle (HA) and Ferric Hydroxide Macro Aggregated (FHMA of high stability and uniformity in particle size and of good geometrical shape suitable for production of radiolabeled carrier for radiation synovectomy purpose were developed. 165Dy, 166Ho and/or 153Sm labeled HA and FHMA were produced using a simple labelling method. (author)

  20. Pain palliative Radiopharmaceuticals

    International Nuclear Information System (INIS)

    A pain relieving agents based on β emitters mainly and in some cases a complex preparation are being given for bone metastasis in relation with breast,prostate and lung carcinoma with good performance in clinical practice.Several radionuclides and radiopharmaceuticals are mentioned giving strength to those newly proposed, 153Sm and 186Re.Bibliography

  1. Samarium-153 therapy for prostate cancer: the evaluation of urine activity, staff exposure and dose rate from patients

    International Nuclear Information System (INIS)

    The aim of this study was to determine the excretion of Samarium-153-ethylenediaminetetra-methylphosphonic acid (153Sm-EDTMP) in urine and to calculate the dose rate of its retention in the body as a function of time and the dose received by the skin of laboratory staff's finger. Urine samples were collected from 11 patients after intravenous injection of 153Sm-EDTMP. The measurements of dose rate were performed. Thermoluminescent dosemeters were used for absorbed dose measurements. Effective half-lives that were calculated from urine sample measurements were found as 7.1±3 h within the first 24 h. Whole body dose rates before collecting urine of patients were 60.0 ± 15.7 μSv h-1 for within 1 h following 153Sm-EDTMP administration. The highest finger radiation dose is to the right-hand thumb (3.8 ± 2 mGy). The results of the study imply that patients who received 153Sm-EDTMP therapy should be kept a minimum of 8 h in an isolated room at hospital and that one staff should give therapy at most two patients per week. (authors)

  2. Metal-ion Speciation in Blood Plasma as a Tool in Predicting the "in vivo" Behaviour of Potential Bone-Seeking Radiopharmaceuticals

    NARCIS (Netherlands)

    Zeevaart, J.R.

    2001-01-01

    In a quest for more effective radiopharmaceuticals for palliation of pain experienced by metastatic bone cancer patients, results obtained with the therapeutic radionuclides 153 SM, 166 Ho and 117mSn complexed to bone-seeking phopsphate ligands are related. As phosphonates are known to enhance the r

  3. Characterization of ceramic seeds with samarium-153 for use in brachytherapy

    Directory of Open Access Journals (Sweden)

    Eduardo Sarmento Valente

    2011-03-01

    Full Text Available Ceramic seeds were synthesized by the sol-gel technique with Si:Sm:Ca. One sample was irradiated in the TRIGA nuclear reactor IPR-R1. After irradiation, the seeds were submitted to instrumental neutron activation analysis to determine the 153Sm concentration in weight. The same irradiated seed sample was submitted to gamma spectrometry analysis to determine all existing radionuclides as well as its individual activities. A second sample was submitted to ICP-AES atomic emission spectrometry. A third sample was submitted to X-ray fluorescence spectrometry to determine qualitative chemical composition. The measured activity was due to 153Sm with a well-characterized gamma spectrum. The X-ray fluorescence spectrum demonstrates that there is no discrepancy in seed composition. Maximum range of beta particles from 153Sm were evaluated, as well as the total dose and dose rate on its range´s volume. The results are relevant for investigation of the viability of producing 153Sm radioactive seeds for use in brachytherapy.

  4. Predictive patient-specific dosimetry and individualized dosing of pretargeted radioimmunotherapy in patients with advanced colorectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Schoffelen, Rafke; Woliner-van der Weg, Wietske; Visser, Eric P.; Oyen, Wim J.G.; Boerman, Otto C. [Radboud University Medical Center, Department of Radiology and Nuclear Medicine, PO Box 9101, Nijmegen (Netherlands); Goldenberg, David M. [Garden State Cancer Center, Morris Plains, NJ (United States); Immunomedics, Inc., Morris Plains, NJ (United States); IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Sharkey, Robert M.; McBride, William J.; Chang, Chien-Hsing [Immunomedics, Inc., Morris Plains, NJ (United States); Rossi, Edmund A. [IBC Pharmaceuticals, Inc., Morris Plains, NJ (United States); Graaf, Winette T.A. van der [Radboud University Medical Center, Department of Medical Oncology, Nijmegen (Netherlands)

    2014-08-15

    Pretargeted radioimmunotherapy (PRIT) with bispecific antibodies (bsMAb) and a radiolabeled peptide reduces the radiation dose to normal tissues. Here we report the accuracy of an {sup 111}In-labeled pretherapy test dose for personalized dosing of {sup 177}Lu-labeled IMP288 following pretargeting with the anti-CEA x anti-hapten bsMAb, TF2, in patients with metastatic colorectal cancer (CRC). In 20 patients bone marrow absorbed doses (BMD) and doses to the kidneys were predicted based on blood samples and scintigrams acquired after {sup 111}In-IMP288 injection for individualized dosing of PRIT with {sup 177}Lu-IMP288. Different dose schedules were studied, varying the interval between the bsMAb and peptide administration (5 days vs. 1 day), increasing the bsMAb dose (75 mg vs. 150 mg), and lowering the peptide dose (100 μg vs. 25 μg). TF2 and {sup 111}In/{sup 177}Lu-IMP288 clearance was highly variable. A strong correlation was observed between peptide residence times and individual TF2 blood concentrations at the time of peptide injection (Spearman's ρ = 0.94, P < 0.0001). PRIT with 7.4 GBq {sup 177}Lu-IMP288 resulted in low radiation doses to normal tissues (BMD <0.5 Gy, kidney dose <3 Gy). Predicted {sup 177}Lu-IMP288 BMD were in good agreement with the actual measured doses (mean ± SD difference -0.0026 ± 0.028 mGy/MBq). Hematological toxicity was mild in most patients, with only two (10 %) having grade 3-4 thrombocytopenia. A correlation was found between platelet toxicity and BMD (Spearman's ρ = 0.58, P = 0.008). No nonhematological toxicity was observed. These results show that individual high activity doses in PRIT in patients with CEA-expressing CRC could be safely administered by predicting the radiation dose to red marrow and kidneys, based on dosimetric analysis of a test dose of TF2 and {sup 111}In-IMP288. (orig.)

  5. 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

  6. 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

  7. Samarium oxide as a radiotracer to evaluate the in vivo biodistribution of PLGA nanoparticles

    Energy Technology Data Exchange (ETDEWEB)

    Mandiwana, Vusani, E-mail: VMandiwana@csir.co.za; Kalombo, Lonji, E-mail: LKalombo@csir.co.za [Centre of Polymers and Composites, CSIR (South Africa); Venter, Kobus, E-mail: Kobus.Venter@mrc.ac.za [South African Medical Research Council (South Africa); Sathekge, Mike, E-mail: Mike.Sathekge@up.ac.za [University of Pretoria and Steve Biko Academic Hospital, Department of Nuclear Medicine (South Africa); Grobler, Anne, E-mail: Anne.Grobler@nwu.ac.za; Zeevaart, Jan Rijn, E-mail: zeevaart@necsa.co.za [North-West University, DST/NWU Preclinical Drug Development Platform (South Africa)

    2015-09-15

    Developing nanoparticulate delivery systems that will allow easy movement and localization of a drug to the target tissue and provide more controlled release of the drug in vivo is a challenge in nanomedicine. The aim of this study was to evaluate the biodistribution of poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles containing samarium-153 oxide ([{sup 153}Sm]Sm{sub 2}O{sub 3}) in vivo to prove that orally administered nanoparticles alter the biodistribution of a drug. These were then activated in a nuclear reactor to produce radioactive {sup 153}Sm-loaded-PLGA nanoparticles. The nanoparticles were characterized for size, zeta potential, and morphology. The nanoparticles were orally and intravenously (IV) administered to rats in order to trace their uptake through imaging and biodistribution studies. The {sup 153}Sm-loaded-PLGA nanoparticles had an average size of 281 ± 6.3 nm and a PDI average of 0.22. The zeta potential ranged between 5 and 20 mV. The [{sup 153}Sm]Sm{sub 2}O{sub 3} loaded PLGA nanoparticles, orally administered were distributed to most organs at low levels, indicating that there was absorption of nanoparticles. While the IV injected [{sup 153}Sm]Sm{sub 2}O{sub 3}-loaded PLGA nanoparticles exhibited the highest localization of nanoparticles in the spleen (8.63 %ID/g) and liver (3.07 %ID/g), confirming that nanoparticles are rapidly removed from the blood by the RES, leading to rapid uptake in the liver and spleen. From the biodistribution data obtained, it is clear that polymeric nanoscale delivery systems would be suitable for improving permeability and thus the bioavailability of therapeutic compounds.

  8. Development of radiopharmaceutical for radiosinovectomy

    International Nuclear Information System (INIS)

    Radiopharmaceuticals prepared with different radionuclides have been used in diagnostic and therapeutic procedures in Nuclear Medicine. The interest in radionuclidic therapy has been increased in last years, with the introduction of new radiopharmaceuticals applied in the destruction of specific cells or to prevent its undesired proliferation. Radiosinovectomy (RSV) is a therapeutic modality that uses radiopharmaceuticals administered in the intra-articular cavity and represents an alternative to the treatment of different arthropaties and, in particular, the arthropaties derived from rheumatoid arthritis and haemophilic. The objective of the present work was to study the labeling of compounds with 90Y and 177Lu in order to improve the production conditions and quality control procedures, study the stability of the labeled compounds and preliminary biodistribution studies of the radiopharmaceuticals with potential for RSV applications. The study of the production of 90Y citrate colloid (90Y-Cit) was based in a labeling procedure using 90Y Cl3 solution (37 - 54 MBq) that was previously dried, followed by the addition of yttrium nitrate and sodium citrate in p H 7 at 37 deg C for 30 minutes. The production of hydroxyapatite (HA) labeled with 90Y was based in a labeling procedure using mono hydrated citric acid, yttrium nitrate and 90Y Cl3 solution (37 - 370 MBq). The reaction mixture was incubated for 30 minutes at room temperature and the HA was introduced in aqueous medium and the reaction proceed for 30 minutes under strong stirring. 177Lu-HA was produced using 177Lu Cl3 solution (296 MBq), in presence of lutetium oxide in NaCl medium, p H 7, under continuous stirring for 30 minutes at room temperature. Several reaction parameters were studied for the three radiopharmaceuticals. Labeling yield was determined after particles were centrifuged and washed with NaCl 0,9%. Radiochemical purity was determined by ascending chromatography using different chromatographic

  9. 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.).

  10. Multi-functional system of radiotherapy and thermal phototherapy for tumors that over-express receptors of the gastrin releasing peptide

    International Nuclear Information System (INIS)

    The aim of this research was to prepare and characterize a multifunctional system of 177Lu and 99mTc-labelled gold nanoparticles conjugated to Tat(49 57)-Lys3 bombesin (177Lu/99mTc- 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 99mTc was carried out through the ligand HYNIC-TOC and with the 177Lu 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 the -Sh groups. The radiochemical purity

  11. 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

  12. Study of the viability of the production of lutetium - 177 in the nuclear reactor IEA-R1 at IPEN/CNEN-SP

    International Nuclear Information System (INIS)

    The - emitter 177 Lu is a promising therapeutic radioisotope for the curative treatment of cancer using labelled proteins. It has a half - life of 6.71 day and maximum and average (3 energies of 421 and 133 keV, respectively, resulting in a short range of irradiation of tissue. The decay is accompanied by the emission of low energy -radiation of 208.3 keV (11%) and 113 keV (6.4%), suitable for simultaneous imaging. Lu can be produced by two different routes, namely, by irradiation of natural Lu2O3 target (176Lu, 2.6%) or enriched (in 176Lu) Lu2O3 target, and also by irradiation of Yb target (Yb2O3) followed by radiochemical separation of Lu from Yb isotopes. The objective of this work is the development of a method of the production of 177 Lu through of the (n, gamma) nuclear reaction, by the direct and indirect method of production. Targets of lutetium oxide and ytterbium oxide were irradiated for evaluation of the activity produced and the chemical separation of lutetium and ytterbium was studied using different ion exchange resins. For the direct method, the best results were obtained using the target Lu2O3 enriched in 39.6%. The best results for the indirect method were achieved with the process of separation using 0.25M - HlBA as eluent. The results showed that it is possible to produce 177 Lu of low specific activity for labeling molecules used for bone pain relief and in radiosynoviortesy. (author)

  13. Development of a new anti-cancer agent for targeted radionuclide therapy: β- radiolabeled RAFT-RGD

    International Nuclear Information System (INIS)

    β-emitters radiolabeled RAFT-RGD as new agents for internal targeted radiotherapy. The αvβ3 integrin is known to play an important role in tumor-induced angiogenesis, tumor proliferation, survival and metastasis. Because of its overexpression on neo-endothelial cells such as those present in growing tumors, as well as on tumor cells of various origins, αvβ3 integrin is an attractive molecular target for diagnosis and therapy of the rapidly growing and metastatic tumors. A tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets integrin αvβ3 in vitro and in vivo. RAFT-RGD has been used for tumor imaging and drug targeting. This study is the first to evaluate the therapeutic potential of the β-emitters radiolabeled tetrameric RGD peptide RAFT-RGD in a Nude mouse model of αvβ3 -expressing tumors. An injection of 37 MBq of 90Y-RAFT-RGD or 177Lu-RAFT-RGD in mice with αvβ3 -positive tumors caused a significant growth delay as compared with mice treated with 37 MBq of 90Y-RAFT-RAD or 177Lu-RAFT-RAD or untreated mice. In comparison, an injection of 30 MBq of 90Y-RAFT-RGD had no efficacy for the treatment of αvβ3 -negative tumors. 90Y-RAFT-RGD and 177Lu-RAFT-RGD are potent αvβ3 -expressing tumor targeting agents for internal targeted radiotherapy. (author)

  14. 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. PMID:26683134

  15. 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.

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

    International Nuclear Information System (INIS)

    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 177Lu, 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 177Lu-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 177LuCl3 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)

  17. The value of samarium-153-EDTMP in breast cancer with bone metastases

    International Nuclear Information System (INIS)

    Objective: This study was to evaluate the efficacy of Samarium-153-EDTMP in breast cancer with bone metastases. Methods: 438 cases with advanced breast cancer that had metastatic bone pain were treated with 153Sm-EDTMP at a dosage of 25.9 MBq/Kg once a month. One course of treatment was 3 to 4 times. Results: The results were evaluated according to the degree of pain relief, mobility, analgesic intake and general feeling. 52.7% (231/438) of patients got complete remission and 33.8% (148/438) incomplete remission. There was no response in the remaining 13.8% (59/438). 52 cases had improved bone scan findings. Conclusion: Palliative treatment of metastatic bone pain from breast cancer with 153Sm-EDTMP improves the quality of life and may be safely repeated with the same benefit and without significant myelosuppression

  18. Novel heterobimetallic radiotheranostic: preparation, activity, and biodistribution.

    Science.gov (United States)

    Adriaenssens, Louis; Liu, Qiang; Chaux-Picquet, Fanny; Tasan, Semra; Picquet, Michel; Denat, Franck; Le Gendre, Pierre; Marques, Fernanda; Fernandes, Célia; Mendes, Filipa; Gano, Lurdes; Campello, Maria Paula Cabral; Bodio, Ewen

    2014-07-01

    A novel Ru(II) (arene) theranostic complex is presented. It is based on a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid macrocycle bearing a triarylphosphine and can be tracked in vivo by using the γ emission of (153) Sm atoms. Notably, the heteroditopic ligand can be selectively metalated with ruthenium at the phosphorus atom despite the presence of other functionalities that are prone to metal coordination. Subsequent labeling with radionuclides such as (153) Sm can then be performed easily. The resulting heterobimetallic complex exhibits favorable solubility and stability properties in biologically relevant media. It also shows in vitro cytotoxicity in line with that expected for this type of metallodrug, and is nontoxic to the organism as a whole. As a proof of concept, initial studies in healthy mice were performed to obtain information about the uptake, biodistribution, and excretion of the radiolabeled complex. PMID:24449620

  19. Present status of OAP radioisotope production

    International Nuclear Information System (INIS)

    Radioisotope Production Program (RP), Office of Atoms for Peace (OAP) is a non-profit government organization which responsible for research development and service of radioisotopes. Several research works on radioisotope production have been carried on at OAP. The radioisotope products of successful R and D have been routinely produced to supply for medical, agriculture and research application. The main products are 131I (solution and capsule), 131I-MIBG, 131I-Hippuran, 153Sm-EDTMP, 153Sm-HA, and 99mTc-radiopharmaceutical kits to serve local users. Radioisotopes are very beneficial for science and human welfare so as almost of our products and services are mainly utilized for medical purpose for both diagnosis and therapy. OAP has a policy to serve and response to that community by providing radioisotopes and services with high quality but reasonable price. This policy will give the opportunity to the community to utilize these radioisotopes for their healthcare. (author)

  20. Metastatic superscan in prostate carcinoma on gallium-68-prostate-specific membrane antigen positron emission tomography/computed tomography scan

    Science.gov (United States)

    Agarwal, Krishan Kant; Tripathi, Madhavi; Kumar, Rajeev; Bal, Chandrasekhar

    2016-01-01

    We describe the imaging features of a metastatic superscan on gallium-68 Glu-NH-CO-NH-Lys-(Ahx)-[Ga-68(HBED-CC)], abbreviated as gallium-68-prostate-specific membrane antigen (68Ga-PSMA) positron emission tomography/computed tomography (PET/CT) imaging. 68Ga-PSMA is novel radiotracer undergoing evaluation for PET/CT imaging of prostate carcinoma. This patient had a superscan of metastases on conventional bone scintigraphy and was referred for 68Ga-PSMA PET/CT to evaluate the feasibility of 177Lu-PSMA therapy. PMID:27095868

  1. 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...

  2. Investigation of the chick embryo as a potential alternative to the mouse for evaluation of radiopharmaceuticals

    International Nuclear Information System (INIS)

    Introduction: The chick embryo is an emerging in vivo model in several areas of pre-clinical research including radiopharmaceutical sciences. Herein, it was evaluated as a potential test system for assessing the biodistribution and in vivo stability of radiopharmaceuticals. For this purpose, a number of radiopharmaceuticals labeled with 18F, 125I, 99mTc, and 177Lu were investigated in the chick embryo and compared with the data obtained in mice. Methods: Chick embryos were cultivated ex ovo for 17–19 days before application of the radiopharmaceutical directly into the peritoneum or intravenously using a vein of the chorioallantoic membrane (CAM). At a defined time point after application of radioactivity, the embryos were euthanized by shock-freezing using liquid nitrogen. Afterwards they were separated from residual egg components for post mortem imaging purposes using positron emission tomography (PET) or single photon emission computed tomography (SPECT). Results: SPECT images revealed uptake of [99mTc]pertechnetate and [125I]iodide in the thyroid of chick embryos and mice, whereas [177Lu]lutetium, [18F]fluoride and [99mTc]-methylene diphosphonate ([99mTc]-MDP) were accumulated in the bones. [99mTc]-dimercaptosuccinic acid (99mTc-DMSA) and the somatostatin analog [177Lu]-DOTATOC, as well as the folic acid derivative [177Lu]-DOTA-folate showed accumulation in the renal tissue whereas [99mTc]-mebrofenin accumulated in the gall bladder and intestine of both species. In vivo dehalogenation of [18F]fallypride and of the folic acid derivative [125I]iodo-tyrosine-folate was observed in both species. In contrast, the 3′-aza-2′-[18F]fluorofolic acid ([18F]-AzaFol) was stable in the chick embryo as well as in the mouse. Conclusions: Our results revealed the same tissue distribution profile and in vivo stability of radiopharmaceuticals in the chick embryo and the mouse. This observation is promising with regard to a potential use of the chick embryo as an inexpensive

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

    International Nuclear Information System (INIS)

    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 90Y-DOTATOC, multiple re-treatment cycles with 177Lu-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 177Lu-DOTATATE with granted orphan designation, the company Advanced Accelerator Applications (AAA) is currently running a phase III study comparing treatment with 177Lu-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 90Y-DOTATOC, 177Lu-DOTATOC and the 68Ga-labelled somatostatin antagonist OPS202, these developments promote the advancement of PRRT and PET imaging. PRRT experience is limited to single

  4. 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

  5. Production of medically relevant radionuclides with medium energy deuterons

    International Nuclear Information System (INIS)

    Radioisotopes used in medical practice and for industrial or research applications are often produced with charged particle induced reactions. Although mostly proton beams are used, the cross sections of deuteron induced reactions are sometimes higher and lead to higher thick target production rates. For 13 targets, ranging from mass 61 to 176, an experimental comparison between cross sections and thick target yields for (p,n) and (d,2n) reactions were made. Three examples, leading to 64Cu, 103Pd and 186Re, respectively, are discussed in detail as well as the production of 99Mo and 177Lu by deuteron induced reactions. (authors)

  6. The characteristic of complications of radionuclide therapy by samarium oksabifor at oncologic patients

    International Nuclear Information System (INIS)

    On the basis of data of clinical-laboratory evaluation of 30 oncologic patients with bone metastasis the account and the analysis of complications of radio nuclide therapy (RNT) by samarium-oksabifor are carried out. It is defined that RNT 153Sm increases efficiency of complex palliative treatment of patients with bone metastasis, has high tolerability and isn't followed by intensifying of frequency of radial reactions and complications

  7. Characterization of ceramic seeds with samarium-153 for use in brachytherapy

    OpenAIRE

    Eduardo Sarmento Valente; Ethel Mizrahy Cuperschmid; Tarcísio Passos Ribeiro de Campos

    2011-01-01

    Ceramic seeds were synthesized by the sol-gel technique with Si:Sm:Ca. One sample was irradiated in the TRIGA nuclear reactor IPR-R1. After irradiation, the seeds were submitted to instrumental neutron activation analysis to determine the 153Sm concentration in weight. The same irradiated seed sample was submitted to gamma spectrometry analysis to determine all existing radionuclides as well as its individual activities. A second sample was submitted to ICP-AES atomic emission spectrometry. A...

  8. Internal radiation dosimetry of orally administered radiotracers for the assessment of gastrointestinal motility

    International Nuclear Information System (INIS)

    Radionuclide imaging using 111In, 99mTc and 153Sm is commonly undertaken for the clinical investigation of gastric emptying, intestinal motility and whole gut transit. However the documented evidence concerning internal radiation dosimetry for such studies is not readily available. This communication documents the internal radiation dosimetry for whole gastrointestinal transit studies using 111In, 99mTc and 153Sm labeled formulations. The findings were compared to the diagnostic reference levels recommended by the United Kingdom Administration of Radioactive Substances Advisory Committee, for gastrointestinal transit studies. - Highlights: • Internal radiation dose estimates for radionuclide GI transit were calculated. • The ICRP 30 GI tract model, MIRDOSE 3.1 and OLINDA/EXM 1.0 software applications were used. • The calculated equivalent dose and effective dose for organs were reported. • The radiation doses among 153Sm, 111In and 99mTc formulations were compared. • The calculated doses were in good agreement with the ARSAC published values

  9. Optimization of production and quality control of therapeutic radionuclides and radiopharmaceuticals. Final report of a co-ordinated research project 1994-1998

    International Nuclear Information System (INIS)

    The 'renaissance' of the therapeutic applications of radiopharmaceuticals during the last few years was in part due to a greater availability of radionuclides with appropriate nuclear decay properties, as well as to the development of carrier molecules with improved characteristics. Although radionuclides such as 32P, 89Sr and 131I, were used from the early days of nuclear medicine in the late 1930s and early 1940s, the inclusion of other particle emitting radionuclides into the nuclear medicine armamentarium was rather late. Only in the early 1980s did the specialized scientific literature start to show the potential for using other beta emitting nuclear reactor produced radionuclides such as 153Sm, 166 Ho, 165Dy and 186-188Re. Bone seeking agents radiolabelled with the above mentioned beta emitting radionuclides demonstrated clear clinical potential in relieving intense bone pain resulting from metastases of the breast, prostate and lung of cancer patients. Therefore, upon the recommendation of a consultants meeting held in Vienna in 1993, the Co-ordinated Research Project (CRP) on Optimization of the Production and quality control of Radiotherapeutic Radionuclides and Radiopharmaceuticals was established in 1994. The CRP aimed at developing and improving existing laboratory protocols for the production of therapeutic radionuclides using existing nuclear research reactors including the corresponding radiolabelling, quality control procedures; and validation in experimental animals. With the participation of ten scientists from IAEA Member States, several laboratory procedures for preparation and quality control were developed, tested and assessed as potential therapeutic radiopharmaceuticals for bone pain palliation. In particular, the CRP optimised the reactor production of 153Sm and the preparation of the radiopharmaceutical 153Sm-EDTMP (ethylene diamine tetramethylene phosphonate), as well as radiolabelling techniques and quality control methods for the

  10. Automated synthesis, characterization and biological evaluation of [{sup 68}Ga]Ga-AMBA, and the synthesis and characterization of {sup nat}Ga-AMBA and [{sup 67}Ga]Ga-AMBA

    Energy Technology Data Exchange (ETDEWEB)

    Cagnolini, Aldo; Chen Jianqing; Ramos, Kimberly; Marie Skedzielewski, Tina; Lantry, Laura E.; Nunn, Adrian D.; Swenson, Rolf E. [Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, NJ 08540 (United States); Linder, Karen E., E-mail: karen.e.linder@gmail.co [Ernst Felder Laboratories, Bracco Research USA Inc., 305 College Road East, Princeton, NJ 08540 (United States)

    2010-12-15

    Ga-AMBA (Ga-DO3A-CH{sub 2}CO-G-[4-aminobenzoyl]-QWAVGHLM-NH{sub 2}) is a bombesin-like agonist with high affinity for gastrin releasing peptide receptors (GRP-R). Syntheses for {sup nat}Ga-AMBA, [{sup 67}Ga]Ga-AMBA and [{sup 68}Ga]Ga-AMBA were developed. The preparation of HPLC-purified and Sep-Pak purified [{sup 68}Ga]Ga-AMBA were fully automated, using the built-in radiodetector of the Tracerlab FX F-N synthesizer to monitor fractionated {sup 68}Ge/{sup 68}Ga generator elution and purification. The total synthesis time, including the fractional elution of the generator, was 20 min for Sep-Pak purified material and 40 min for HPLC-purified [{sup 68}Ga]Ga-AMBA. Both [{sup 67}Ga]Ga-AMBA and [{sup 177}Lu]Lu-AMBA showed comparable high affinity for GRP-R in the human prostate cancer cell line PC-3 in vitro (k{sub D}=0.46{+-}0.07; 0.44{+-}0.08 nM), high internalization (78; 77%) and low efflux from cells at 2 h (2.4{+-}0.7; 2.9{+-}1.8%). Biodistribution results in PC-3 tumor-bearing male nude mice showed comparable uptake for [{sup 177}Lu]Lu-, [{sup 111}In]In-, [{sup 67}Ga]Ga- and [{sup 68}Ga]Ga-AMBA.

  11. 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.

  12. {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.)

  13. 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)

  14. Labelling of the peptide Dota-Octreotate with Lutetium 177

    International Nuclear Information System (INIS)

    In this work is described the optimization of the reaction conditions to obtain the complex 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 μg / 37 MBq) obtained in the irradiation of 176 Lu2O3 it allowed to verify the union of the 177Lu-Dota-Tate to membrane receivers but without being able to obtain the saturation curves and competition required to characterize quantitatively the biological recognition. (Author)

  15. 213Bi-DOTATOC receptor-targeted alpha-radionuclide therapy induces remission in neuroendocrine tumours refractory to beta radiation: a first-in-human experience

    International Nuclear Information System (INIS)

    Radiopeptide therapy using a somatostatin analogue labelled with a beta emitter such as 90Y/177Lu-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 213Bi-DOTATOC targeted alpha therapy (TAT) in patients pretreated with beta emitters. Seven patients with progressive advanced neuroendocrine liver metastases refractory to treatment with 90Y/177Lu-DOTATOC were treated with an intraarterial infusion of 213Bi-DOTATOC, and one patient with bone marrow carcinosis was treated with a systemic infusion of 213Bi-DOTATOC. Haematological, kidney and endocrine toxicities were assessed according to CTCAE criteria. Radiological response was assessed with contrast-enhanced MRI and 68Ga-DOTATOC-PET/CT. More than 2 years of follow-up were available in seven patients. The biodistribution of 213Bi-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.)

  16. Protective role of intracellular superoxide dismutase against extracellular oxidants in cultured rat gastric cells.

    OpenAIRE

    Hiraishi, H; Terano, A; Sugimoto, T.; Harada, T; Razandi, M; Ivey, K J

    1994-01-01

    We examined the role of intracellular superoxide dismutase (SOD) as an antioxidant by studying the effect of diethyldithiocarbamate (DDC) on extracellular H2O2-induced damage in cultured rat gastric mucosal cells. 51Cr-labeled monolayers from rat stomachs were exposed to glucose oxidase-generated H2O2 or reagent H2O2, which both caused a dose-dependent increase in 51Cr release. DDC dose-dependently enhanced 51Cr release by hydrogen peroxide, corresponding with inhibition of endogenous SOD act...

  17. Organ distribution of sheep red blood cells in ALS-treated rats.

    Science.gov (United States)

    Kinnaert, P; Mahieu, A; Van Geertruyden, N; d'Orchimont, R; Goossens, R

    1975-01-01

    The inter-organ distribution of radioactivity in rats injected with 51Cr-labelled SRBC is altered after treatment with ALS absorbed with this antigen. The alteration is due to the presence of soluble SRBC antigens in the serum and subsequent immunization of the tested animals. The 51Cr distribution does not correspond to the uptake of antigenic material in immunized rats. PMID:1165111

  18. Antibody-dependent cell-mediated cytotoxicity (ADCC) toward human O+ red cells coated with anti-D antibody: comparison between lymphocyte and monocyte ADCC activity.

    OpenAIRE

    Sunada,Mitsutoshi; Suzuki, Shinya; Ota, Zensuke

    1985-01-01

    We investigated the antibody dependent cell-mediated cytotoxicity (ADCC) of lymphocytes and monocytes toward human O+ red cells coated with anti-D antibody using a 51Cr release assay. Lysis of sensitized red cells by lymphocytes occurred rapidly, but monocyte-mediated lysis occurred slowly. This difference might be due to postphagocytic 51Cr release by monocytes. ADCC of lymphocytes increased in proportion to the effector cell number, but large amounts of antibodies were required. In contrast...

  19. Experimental non-steroidal anti-inflammatory drug-induced enteropathy in the rat: similarities to inflammatory bowel disease and effect of thromboxane synthetase inhibitors.

    OpenAIRE

    Banerjee, A K; Peters, T. J.

    1990-01-01

    We have validated an established animal model of acute inflammatory bowel disease in indomethacin-treated rats. Studies in both in vitro and in vivo 51chromium-labelled ethylenediamine tetra-acetate (51Cr-EDTA) permeability and tissue myeloperoxidase activity, a marker of inflammatory cell invasion, showed increased permeability and enzyme levels, respectively, in treated animals compared to controls (in vitro 51Cr-EDTA permeability: (mean (SE] control 0.10 (0.02) microliter/mg per tissue, ex...

  20. 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....

  1. Single-dose anti-CD138 radioimmunotherapy: bismuth-213 is more efficient than lutetium-177 for treatment of multiple myeloma in a preclinical model

    Directory of Open Access Journals (Sweden)

    Nolwenn eFichou

    2015-11-01

    Full Text Available Objectives: Radioimmunotherapy (RIT has emerged as a potential treatment option for multiple myeloma (MM. In humans, a dosimetry study recently showed the relevance of RIT using an antibody targeting the CD138 antigen. The therapeutic efficacy of RIT using an anti-CD138 antibody coupled to 213Bi, an α-emitter, was also demonstrated in a preclinical MM model. Since then, RIT with β-emitters has shown efficacy in treating hematologic cancer. In this paper, we investigate the therapeutic efficacy of RIT in the 5T33 murine MM model using a new anti-CD138 monoclonal antibody labeled either with 213Bi for α-RIT or 177Lu for β-RIT.Methods: A new monoclonal anti-CD138 antibody, 9E7.4, was generated by immunizing a rat with a murine CD138-derived peptide. Antibody specificity was validated by flow cytometry, biodistribution and α-RIT studies. Then, a β-RIT dose-escalation assay with the 177Lu-radiolabeled 9E7.4 mAb was performed in KalwRij C57/BL6 mice 10 days after i.v. engraftment with 5T33 MM cells. Animal survival and toxicological parameters were assessed to define the optimal activity.Results: α-RIT performed with 3.7 MBq of 213Bi-labeled 9E7.4 anti-CD138 mAb increased median survival to 80 days compared to 37 days for the untreated control and effected cure in 45% of animals. β-RIT performed with 18.5 MBq of 177Lu-labeled 9E7.4 mAb was well tolerated and significantly increased mouse survival (54 versus 37 days in the control group; however, no mice were cured with this treatment.Conclusion: This study revealed the advantages of α-RIT in the treatment of MM in a preclinical model where β-RIT shows almost no efficacy.

  2. Synthesis and in vivo evaluation of {sup 201}Tl(III)-DOTA complexes for applications in SPECT imaging

    Energy Technology Data Exchange (ETDEWEB)

    Hijnen, Nicole M.; Vries, Anke de [Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Blange, Roy [Department of Biomolecular Engineering, Antwerp University, 2610 Antwerp (Belgium); Burdinski, Dirk [Department of Biomolecular Engineering, Philips Research, 5656 AE Eindhoven (Netherlands); Gruell, Holger, E-mail: h.gruell@tue.n [Biomedical NMR, Department of Biomedical Engineering, Eindhoven University of Technology, 5600 MB Eindhoven (Netherlands); Department of Biomolecular Engineering, Philips Research, 5656 AE Eindhoven (Netherlands)

    2011-05-15

    Introduction: The aim of this study was to assess the use of {sup 201}thallium{sup 3+} ({sup 201}Tl{sup 3+}) as a radiolabel for nuclear imaging tracers. Methods for labeling of 1,4,7,10-tetraazacyclododecane-N,N',N'',N''' tetraacetic acid (DOTA) and diethylenetriaminepentaacetic acid (DTPA) chelators with {sup 201}Tl{sup 3+} were investigated, and the levels of stability of these chelates were tested in vitro and in vivo. Methods: {sup 201}Tl(I)Cl was treated with hydrochloric acid and ozone to form {sup 201}Tl(III)Cl{sub 3}. The procedure for labeling of DOTA and DTPA was optimized, testing different buffer solutions and pH values. The stability levels of {sup 201}Tl(III)-DOTA and {sup 201}Tl(III)-DTPA were assessed in buffer, mouse serum and human serum (1:1, v/v) at a temperature of 310 K for 48 h. Subsequently, in vivo stability studies with {sup 201}Tl(III)-DOTA were performed, comparing the biodistribution of {sup 201}Tl(III)-DOTA with that of {sup 201}Tl(I)Cl in a single-isotope study and with that of {sup 177}Lu(III)-DOTA in a dual-isotope single photon emission computed tomography study. Results: {sup 201}Tl(III)-DTPA, {sup 201}Tl(III)-DOTA and {sup 177}Lu(III)-DOTA were prepared with >95% radiochemical purity. While {sup 201}Tl(III)-DOTA showed a prolonged level of stability in buffer and serum, {sup 201}Tl was quickly released from DTPA in serum. Apart from some urinary excretion, the biodistribution of DOTA-chelated {sup 201}Tl{sup 3+} was similar to that of free (ionic) {sup 201}Tl{sup +} and did not match the biodistribution of {sup 177}Lu(III)-DOTA. This indicated a limited stability of {sup 201}Tl(III)-DOTA complexes in vivo. Conclusion: Despite promising results on the labeling and in vitro stability of {sup 201}Tl(III)-DOTA, our in vivo results indicate that the integrity of {sup 201}Tl(III)-DOTA decreases to <20% during the time required for urinary excretion, thereby limiting the use of {sup 201}Tl{sup 3+} as a

  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. PET SUV correlates with radionuclide uptake in peptide receptor therapy in meningioma

    Energy Technology Data Exchange (ETDEWEB)

    Haenscheid, Heribert; Buck, Andreas K.; Samnick, Samuel; Kreissl, Michael [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); Sweeney, Reinhart A.; Flentje, Michael [University Hospital Wuerzburg, Department of Radiation Oncology, Wuerzburg (Germany); Loehr, Mario [University Hospital Wuerzburg, Department of Neurosurgery, Wuerzburg (Germany); Verburg, Frederik A. [University Hospital Wuerzburg, Department of Nuclear Medicine, Wuerzburg (Germany); RWTH University Hospital Aachen, Department of Nuclear Medicine, Aachen (Germany)

    2012-08-15

    To investigate whether the tumour uptake of radionuclide in peptide receptor radionuclide therapy (PRRT) of meningioma can be predicted by a PET sc