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Sample records for radionuclides 177lu 131i

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

    International Nuclear Information System (INIS)

    Dah, Ashutosh; Pillai, Maroor Raghavan Ambikalmajan; Knapp, Furn F. Jr.

    2015-01-01

    This review provides a comprehensive summary of the production of 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 177 Lu having the required quality for preparation of a variety of 177 Lu-labeled radiopharmaceuticals. The tremendous prospects associated with production of 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 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 177 Lu production and processing approaches would not only ensure sustained growth and future expansion for the availability and use of 177 Lu-labeled radiopharmaceuticals, but also help future developments

  2. The Bad Berka dose protocol: comparative results of dosimetry in peptide receptor radionuclide therapy using (177)Lu-DOTATATE, (177)Lu-DOTANOC, and (177)Lu-DOTATOC.

    Science.gov (United States)

    Schuchardt, Christiane; Kulkarni, Harshad R; Prasad, Vikas; Zachert, Carolin; Müller, Dirk; Baum, Richard P

    2013-01-01

    The objective of this study is to analyze the in vivo behavior of the (177)Lu-labeled peptides DOTATATE, DOTANOC, and DOTATOC used for peptide receptor radionuclide therapy (PRRNT) of neuroendocrine tumors (NETs), by measuring organ and tumor kinetics and by performing dosimetric calculations. Two hundred fifty-three patients (group 1) with metastasized NET who underwent PRRNT were examined. Out of these, 185 patients received (177)Lu-DOTATATE, 9 were treated with (177)Lu-DOTANOC, and 59 with (177)Lu-DOTATOC. Additionally, 25 patients receiving, in consecutive PRRNT cycles, DOTATATE followed by DOTATOC (group 2) and 3 patients receiving DOTATATE and DOTANOC (group 3) were analyzed. Dosimetric calculations (according to MIRD scheme) were performed using OLINDA software. In group 1, DOTATOC exhibited the lowest and DOTANOC the highest uptake and therefore mean absorbed dose in normal organs (whole body, kidney, and spleen). In group 2, there was a significant difference between DOTATATE and DOTATOC concerning kinetics and normal organ doses. (177)Lu-DOTATOC had the lowest uptake/dose delivered to normal organs and highest tumor-to-kidney ratio. There were no significant differences between the three peptides concerning tumor kinetics and mean absorbed tumor dose. The study demonstrates a correlation between high affinity of DOTANOC in vitro and high uptake in normal organs/whole body in vivo, resulting in a higher whole-body dose. DOTATOC exhibited the lowest uptake and dose delivered to normal tissues and the best tumor-to-kidney ratio. Due to large interpatient variability, individual dosimetry should be performed for each therapy cycle.

  3. 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.)

  4. 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.

  5. Blood clearance and occupational exposure for {sup 177}Lu-DOTATATE compared to {sup 177}Lu-PSMA radionuclide therapy

    Energy Technology Data Exchange (ETDEWEB)

    Abuqbeitah, Mohammad; Demir, Mustafa; Uslu-Besli, Lebriz; Yeyin, Nami; Soenmezoglu, Kerim [Istanbul University, Department of Nuclear Medicine, Cerrahpasa Faculty of Medicine, Istanbul (Turkey)

    2018-03-15

    The main target of this work is to examine blood clearance and external exposure for {sup 177}Lu-DOTATATE compared with new emerging {sup 177}Lu-PSMA therapy. Blood clearance and radiation exposure of 31 patients treated with 5.5 ± 1.1 GBq {sup 177}Lu-DOTATATE were compared to those of 23 patients treated with 7.4 GBq {sup 177}Lu-PSMA. Dose rates were measured at several distances and time points up to 120 h after treatment. Blood samples were collected conjunctively after infusion. Caregiver's cumulative dose was measured by means of an OSL (optically stimulated luminescence) dosimeter for 4-5 days and medical staff's dose was also estimated using electronic personal dosimeters. Finger dose was determined via ring TLD (Thermoluminescence Dosimeter) for radiopharmacists and nurses. Dose rates due to {sup 177}Lu-DOTATATE at a distance of 1 m, 4 h and 6 h after infusion, were 3.0 ± 2.8 and 2 ± 1.9 μSv/(h GBq), respectively, while those due to {sup 177}Lu-PSMA were 3.1 ± 0.8 and 2.2 ± 0.9 μSv/(h GBq). Total effective dose of 17 caregivers was 100-200 μSv for {sup 177}Lu-DOTATATE therapy. Mean effective doses to nurses and radiopharmacists were 5 and 4 μSv per patient, respectively, while those for physicists and physicians were 2 μSv per patient. For {sup 177}Lu-DOTATATE, effective half-life in blood and early elimination phase were 0.31 ± 0.13 and 4.5 ± 1 h, while they were found as 0.4 ± 0.1 and 5 ± 1 h, respectively, for {sup 177}Lu-PSMA. The first micturition time following {sup 177}Lu-DOTATATE infusion was noted after 36 ± 14 min, while the second and third voiding times were after 74 ± 9 and 128 ± 41 min, respectively. It is concluded that blood clearance and radiation exposure for {sup 177}Lu-DOTATATE are very similar to those for {sup 177}Lu-PSMA, and both treatment modalities are reasonably reliable for outpatient treatment, since the mean dose rate [2.1 μSv/(h GBq)] decreased below the dose rate that allows release of the patient

  6. Report on the 1. research coordination meeting on 'Development of therapeutic radiopharmaceuticals based on {sup 177}Lu for radionuclide therapy'

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2006-07-01

    Radionuclide therapy (RNT) employing radiopharmaceuticals labelled with emitting radionuclides is fast emerging as an important part of nuclear medicine. Radionuclide therapy is effectively utilized for bone pain palliation, thus providing significant improvement in quality of life of patients suffering from pain resulting from bone metastasis. Targeting primary diseases by using specific carrier molecules labelled with radionuclides is also widely investigated and efficacious products have been emerging for the treatment of Lymphoma and Neuroendocrine tumours. In order to ensure the wider use of radiopharmaceuticals, it is essential to carefully consider the choice of radionuclides that together with the carrier molecules will give suitable pharmacokinetic properties and therapeutic efficacy. The criteria for the selection of a radionuclide for radiotherapy are suitable decay characteristics and amenable chemistry. However, the practical considerations in selecting a radionuclide for targeted therapy are availability in high radionuclidic purity as well as high specific activity and low production cost and comfortable delivery logistics. {sup 177}Lu is one of the isotopes emerging as a clear choice for therapy. Worldwide, the isotope is under investigation for approximately 30 different clinical applications, including treatment of colon cancer, metastatic bone cancer, non-Hodgkin's lymphoma, and lung cancer. {sup 177}Lu decays with a half-life of 6.71 d by emission of particles with E{sub max} of 497 keV (78.6%), 384 keV (9.1%) and 176 keV (12.2%). It also emits photons of 113 keV (6.4%) and 208 keV (11%), that are ideally suited for imaging the in-vivo localization and dosimetric calculations applying a gamma camera. The physical half-life of {sup 177}Lu is comparable to that of {sup 131}I, the most widely used therapeutic radionuclide. The long halflife of {sup 177}Lu provides logistic advantage for production, QA/QC of the products as well as feasibility to

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

    International Nuclear Information System (INIS)

    2006-01-01

    Radionuclide therapy (RNT) employing radiopharmaceuticals labelled with emitting radionuclides is fast emerging as an important part of nuclear medicine. Radionuclide therapy is effectively utilized for bone pain palliation, thus providing significant improvement in quality of life of patients suffering from pain resulting from bone metastasis. Targeting primary diseases by using specific carrier molecules labelled with radionuclides is also widely investigated and efficacious products have been emerging for the treatment of Lymphoma and Neuroendocrine tumours. In order to ensure the wider use of radiopharmaceuticals, it is essential to carefully consider the choice of radionuclides that together with the carrier molecules will give suitable pharmacokinetic properties and therapeutic efficacy. The criteria for the selection of a radionuclide for radiotherapy are suitable decay characteristics and amenable chemistry. However, the practical considerations in selecting a radionuclide for targeted therapy are availability in high radionuclidic purity as well as high specific activity and low production cost and comfortable delivery logistics. 177 Lu is one of the isotopes emerging as a clear choice for therapy. Worldwide, the isotope is under investigation for approximately 30 different clinical applications, including treatment of colon cancer, metastatic bone cancer, non-Hodgkin's lymphoma, and lung cancer. 177 Lu decays with a half-life of 6.71 d by emission of particles with E max of 497 keV (78.6%), 384 keV (9.1%) and 176 keV (12.2%). It also emits photons of 113 keV (6.4%) and 208 keV (11%), that are ideally suited for imaging the in-vivo localization and dosimetric calculations applying a gamma camera. The physical half-life of 177 Lu is comparable to that of 131 I, the most widely used therapeutic radionuclide. The long halflife of 177 Lu provides logistic advantage for production, QA/QC of the products as well as feasibility to supply the products to places

  8. 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)

    Suzauki, Miriam Fussae; Silva, Marcia Augusta da; Caldeira Filho, Jose de Souza; Colturato, Maria Tereza; Araujo, Elaine Bortoleti de; Bartolini, Paolo; Okazaki, Kayo

    2005-01-01

    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, Tyr 3 ]octreotate has been used because of its high affinity to somatostatin subtype receptors sstr 2 and sstr 5 . 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, Tyr 3 ]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, Tyr 3 ]octreotate labeled with with 131 I (n=3) and 177 Lu (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. 131 I and 177 Lu 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) (P 131 I-DOTA, Tyr 3 ]octreotate was Y = (1.634 ± 0.236) + (0.912 ± 0.137) 10 -3 X and for [ 177 Lu-DOTA, Tyr 3 ]octreotate was Y = (1.715 ± 0.342) + (0.743 ± 0.135) 10 -3 X. The non labeled molecule, [DOTA, Tyr 3 ]octreotate, has no influence in the induction of cytogenetic damage. The micronucleus assay with rat pancreatic tumor cells

  9. Targeted radionuclide therapy with A 177Lu-labeled anti-HER2 nanobody.

    Science.gov (United States)

    D'Huyvetter, Matthias; Vincke, Cécile; Xavier, Catarina; Aerts, An; Impens, Nathalie; Baatout, Sarah; De Raeve, Hendrik; Muyldermans, Serge; Caveliers, Vicky; Devoogdt, Nick; Lahoutte, Tony

    2014-01-01

    RIT has become an attractive strategy in cancer treatment, but still faces important drawbacks due to poor tumor penetration and undesirable pharmacokinetics of the targeting vehicles. Smaller radiolabeled antibody fragments and peptides feature highly specific target accumulation, resulting in low accumulation in healthy tissue, except for the kidneys. Nanobodies are the smallest (MWnanobodies is predominantly dictated by the number of polar residues in the C-terminal amino acid tag. Three nanobodies were produced with different C-terminal amino-acid tag sequences (Myc-His-tagged, His-tagged, and untagged). Dynamic planar imaging of Wistar rats with 111In-DTPA-nanobodies revealed that untagged nanobodies showed a 70% drop in kidney accumulation compared to Myc-His-tagged nanobodies at 50 min p.i.. In addition, coinfusion of untagged nanobodies with the plasma expander Gelofusin led to a final reduction of 90%. Similar findings were obtained with different 177Lu-DTPA-2Rs15d nanobody constructs in HER2pos tumor xenografted mice at 1 h p.i.. Kidney accumulation decreased 88% when comparing Myc-His-tagged to untagged 2Rs15d nanobody, and 95% with a coinfusion of Gelofusin, without affecting the tumor targeting capacity. Consequently, we identified a generic method to reduce kidney retention of radiolabeled nanobodies. Dosimetry calculations of Gelofusin-coinfused, untagged 177Lu-DTPA-2Rs15d revealed a dose of 0.90 Gy/MBq that was delivered to both tumor and kidneys and extremely low doses to healthy tissues. In a comparative study, 177Lu-DTPA-Trastuzumab supplied 6 times more radiation to the tumor than untagged 177Lu-DTPA-2Rs15d, but concomitantly also a 155, 34, 80, 26 and 4180 fold higher radioactivity burden to lung, liver, spleen, bone and blood. Most importantly, nanobody-based targeted radionuclide therapy in mice bearing small estiblashed HER2pos tumors led to an almost complete blockade of tumor growth and a significant difference in event-free survival

  10. {sup 177}Lu- labeled MOv18 as compared to {sup 131}I- or {sup 90}Y-labeled MOv18 has the better therapeutic effect in eradication of alpha folate receptor-expressing tumor xenografts

    Energy Technology Data Exchange (ETDEWEB)

    Zacchetti, Alberto [Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133 (Italy); Coliva, Angela [Department of Imaging and Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133 (Italy); Luison, Elena [Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133 (Italy); Seregni, Ettore; Bombardieri, Emilio [Department of Imaging and Nuclear Medicine, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133 (Italy); Giussani, Augusto [Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg (Germany); Figini, Mariangela [Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133 (Italy); Canevari, Silvana [Unit of Molecular Therapies, Department of Experimental Oncology and Laboratories, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan 20133 (Italy)], E-mail: silvana.canevari@istitutotumori.mi.it

    2009-10-15

    Introduction: The mouse monoclonal antibody MOv18, directed against the {alpha}-isoform of folate receptor (FR), was investigated to identify the optimal radioconjugate for radioimmunotherapy of minimal residual disease in ovarian cancer. Methods: Pharmacokinetics, biodistribution, long-term therapeutic efficacy and toxicity of MOv18, labeled with the beta-emitters {sup 131}I, {sup 90}Y and {sup 177}Lu, were compared in a xenografted mouse model, composed by two cell lines, A431FR and A431MK, differing only for FR expression. Results: A shorter blood clearance and a higher tumor uptake were observed for {sup 90}Y- and {sup 177}Lu- compared to {sup 131}I-MOv18, and a shorter blood pharmacokinetics was recorded in A431FR-bearing animals. At equitoxic maximum tolerable doses, the general irradiation by {sup 131}I- and {sup 90}Y-MOv18 gives rise to strong targeted effects on A431FR and nontargeted effects on A431MK tumors, while {sup 177}Lu-MOv18 was able to eradicate small size tumor masses expressing the antigen of interest exerting only mild non-targeted effects. Conclusion: {sup 177}Lu-MOv18 at the maximal tolerated dose is the immunoradioconjugate with the best therapeutic window in experimental conditions of small tumor volume.

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

    International Nuclear Information System (INIS)

    Rolleman, Edgar J.; Forrer, Flavio; Bernard, Bert; Bijster, Magda; Valkema, Roelf; Krenning, Eric P.; Jong, Marion de; Vermeij, Marcel

    2007-01-01

    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 [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Male Lewis rats were injected with 278 or 555 MBq [ 177 Lu-DOTA 0 ,Tyr 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 99m Tc-dimercaptosuccinic acid (DMSA), a measure of tubular function. Treatment with 555 MBq [ 177 Lu-DOTA 0 ,Tyr 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 [ 177 Lu-DOTA 0 ,Tyr 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 99m Tc-DMSA SPECT scintigrams at 130 days after [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate therapy correlated well with 1/creatinine (r 2 = 0.772, p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Besides lysine, amifostine might be used in clinical PRRT as well as to maximise anti-tumour efficacy. (orig.)

  12. Technology of DTPA and immunoglobulins conjugation and their attachment to 90Y and 177Lu radionuclides

    International Nuclear Information System (INIS)

    Rekova, M.; Jedinakova-Krizova, V.

    2010-01-01

    The aim of the study of labeling of ligand-antibody conjugates was to find optimal conditions of preparing of these conjugates and appropriate radioactivity of selected nuclide for applications in nuclear medicine. Conjugation of the γ-immunoglobulin G (human or bovine IgG, polyclonal antibodies) and bifunctional chelating agent, diethylenetriaminepentaacetic acid dianhydride (cDTPAA), was carried out. Various values of the cDTPAA/antibody ratio, the weight concentration of polyclonal or monoclonal antibodies (MEM-97) and buffers were used. Further, the labeling conditions of the DTPA-IgG conjugate by radionuclides 90 Y and 177 Lu were optimized, and the labeling yield and the conjugation ratio of prepared radionuclide-DTPA-IgG conjugates was determined. Optimal incubation time of the immunoglobulin conjugation was obtained at 30 min from mixing of individual components. The labeling yield of radionuclide-DTPA-antibody conjugate higher than 95% was achieved. Higher values of conjugation ratio of radionuclide-DTPA-antibody conjugate were achieved in 0.1 mol L -1 carbonate buffer, pH 8.5, and the 0.1 mol L -1 carbonate buffer is suitable for studied conjugation systems. This study showed that the labeling yield as well as the conjugation ratio of tested systems depend on the amount of antibody substance, bifunctional chelating agent/antibody molar ratio and pH value of the buffer used. (author)

  13. Personalized {sup 177}Lu-octreotate peptide receptor radionuclide therapy of neuroendocrine tumours: a simulation study

    Energy Technology Data Exchange (ETDEWEB)

    Del Prete, Michela; Buteau, Francois-Alexandre; Beauregard, Jean-Mathieu [Laval Univ., QC (Canada). Dept. of Radiology and Nuclear Medicine, and Cancer Research Center; CHU de Quebec - Laval Univ., QC (Canada). Dept. of Medical Imaging, and Oncology Branch of Research Center

    2017-08-15

    Peptide receptor radionuclide therapy (PRRT) with {sup 177}Lu-octreotate is commonly administered at empiric, fixed amounts of injected radioactivity (IA). This results in highly variable absorbed doses to critical organs and suboptimal treatment of most patients. The primary aims of this study were to design a personalized PRRT (P-PRRT) protocol based on dosimetry, and to perform a simulation of this protocol in a retrospective cohort of patients with neuroendocrine tumours, in order to assess the potential of P-PRRT to safely increase the absorbed dose to the tumour during a four-cycle induction course. Thirty-six patients underwent 122 fixed-IA {sup 177}Lu-octreotate PRRT cycles with quantitative SPECT/CT-based dosimetry. Twenty-two patients completed a four-cycle induction course (29.6 ± 2.4 GBq cumulative IA), with kidney, bone marrow and maximum tumour absorbed doses of 16.2 ± 5.5, 1.3 ± 0.8, and 114 ± 66 Gy, respectively. We simulated a P-PRRT regime in which the renal absorbed dose per IA was predicted by the body surface area and glomerular filtration rate for the first cycle, and by renal dosimetry of the previous cycle(s) for the following cycles. Personalized IA was adjusted at each cycle in order to reach the prescribed renal absorbed dose of 23 Gy over four cycles (with a 25-50% reduction when renal or bone marrow function was impaired). Simulated IA and absorbed doses were based on actual patient characteristics, laboratory values and absorbed doses per IA delivered at each cycle. In the P-PRRT regime, cumulative IA could have been increased to 43.7 ± 16.5 GBq over four induction cycles (10.9 ± 5.0 GBq per cycle), yielding cumulative kidney, bone marrow and maximum tumour absorbed doses of 21.5 ± 2.5, 1.63 ± 0.61, and 163.4 ± 85.9 Gy, respectively. This resulted in an average 1.48-fold increase in cumulative maximum tumour absorbed dose over empiric PRRT (range, 0.68-2.64-fold; P = 0.0013). By standardizing the renal absorbed dose delivered

  14. In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy.

    Science.gov (United States)

    Chan, Ho Sze; de Blois, Erik; Morgenstern, Alfred; Bruchertseifer, Frank; de Jong, Marion; Breeman, Wouter; Konijnenberg, Mark

    2017-01-01

    Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE), 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line. Two other cell lines were used for radiation response assessment; BON and CA20948, with a low and high expression of somatostatin receptors, respectively. Cellular uptake kinetics of 111In-DOTATATE were determined in CA20948 cells. CA20948 and BON were irradiated with 137Cs, 177Lu-DTPA, 177Lu-DOTATATE, 213Bi-DTPA and 213Bi-DOTATATE. Absorbed doses were calculated using the MIRDcell dosimetry method for the specific binding and a Monte Carlo model of a cylindrical 6-well plate geometry for the exposure by the radioactive incubation medium. Absorbed doses were compared to conventional irradiation of cells with 137Cs and the relative biological effect (RBE) at 10% survival was calculated. IC50 of (labelled) DOTATATE was in the nM range. Absorbed doses up to 7 Gy were obtained by 5.2 MBq 213Bi-DOTATATE, in majority the dose was caused by α-particle radiation. Cellular internalization determined with 111In-DOTATATE showed a linear relation with incubation time. Cell survival after exposure of 213Bi-DTPA and 213Bi-DOTATATE to BON or CA20948 cells showed a linear-exponential relation with the absorbed dose, confirming the high LET character of 213Bi. The survival of CA20948 after exposure to 177Lu-DOTATATE and the reference 137Cs irradiation showed the typical curvature of the linear-quadratic model. 10% Cell survival of CA20948 was reached at 3 Gy with 213Bi-DOTATATE, a factor 6 lower than the 18 Gy found for 177Lu

  15. In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy.

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    Ho Sze Chan

    Full Text Available Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE, 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line. Two other cell lines were used for radiation response assessment; BON and CA20948, with a low and high expression of somatostatin receptors, respectively. Cellular uptake kinetics of 111In-DOTATATE were determined in CA20948 cells. CA20948 and BON were irradiated with 137Cs, 177Lu-DTPA, 177Lu-DOTATATE, 213Bi-DTPA and 213Bi-DOTATATE. Absorbed doses were calculated using the MIRDcell dosimetry method for the specific binding and a Monte Carlo model of a cylindrical 6-well plate geometry for the exposure by the radioactive incubation medium. Absorbed doses were compared to conventional irradiation of cells with 137Cs and the relative biological effect (RBE at 10% survival was calculated.IC50 of (labelled DOTATATE was in the nM range. Absorbed doses up to 7 Gy were obtained by 5.2 MBq 213Bi-DOTATATE, in majority the dose was caused by α-particle radiation. Cellular internalization determined with 111In-DOTATATE showed a linear relation with incubation time. Cell survival after exposure of 213Bi-DTPA and 213Bi-DOTATATE to BON or CA20948 cells showed a linear-exponential relation with the absorbed dose, confirming the high LET character of 213Bi. The survival of CA20948 after exposure to 177Lu-DOTATATE and the reference 137Cs irradiation showed the typical curvature of the linear-quadratic model. 10% Cell survival of CA20948 was reached at 3 Gy with 213Bi-DOTATATE, a factor 6 lower than the 18 Gy found

  16. The low-energy β(-) and electron emitter (161)Tb as an alternative to (177)Lu for targeted radionuclide therapy.

    Science.gov (United States)

    Lehenberger, Silvia; Barkhausen, Christoph; Cohrs, Susan; Fischer, Eliane; Grünberg, Jürgen; Hohn, Alexander; Köster, Ulli; Schibli, Roger; Türler, Andreas; Zhernosekov, Konstantin

    2011-08-01

    The low-energy β(-) emitter (161)Tb is very similar to (177)Lu with respect to half-life, beta energy and chemical properties. However, (161)Tb also emits a significant amount of conversion and Auger electrons. Greater therapeutic effect can therefore be expected in comparison to (177)Lu. It also emits low-energy photons that are useful for gamma camera imaging. The (160)Gd(n,γ)(161)Gd→(161)Tb production route was used to produce (161)Tb by neutron irradiation of massive (160)Gd targets (up to 40 mg) in nuclear reactors. A semiautomated procedure based on cation exchange chromatography was developed and applied to isolate no carrier added (n.c.a.) (161)Tb from the bulk of the (160)Gd target and from its stable decay product (161)Dy. (161)Tb was used for radiolabeling DOTA-Tyr3-octreotate; the radiolabeling profile was compared to the commercially available n.c.a. (177)Lu. A (161)Tb Derenzo phantom was imaged using a small-animal single-photon emission computed tomography camera. Up to 15 GBq of (161)Tb was produced by long-term irradiation of Gd targets. Using a cation exchange resin, we obtained 80%-90% of the available (161)Tb with high specific activity, radionuclide and chemical purity and in quantities sufficient for therapeutic applications. The (161)Tb obtained was of the quality required to prepare (161)Tb-DOTA-Tyr3-octreotate. We were able to produce (161)Tb in n.c.a. form by irradiating highly enriched (160)Gd targets; it can be obtained in the quantity and quality required for the preparation of (161)Tb-labeled therapeutic agents. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. 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

    The urokinase-type plasminogen activator receptor (uPAR) is implicated in cancer invasion and metastatic development in prostate cancer and provides therefore an attractive molecular target for both imaging and therapy. In this study, we provide the first in vivo data on an antimetastatic effect...... of uPAR radionuclide targeted therapy in such lesions and show the potential of uPAR positron emission tomography (PET) imaging for identifying small foci of metastatic cells in a mouse model of disseminating human prostate cancer. Two radiolabeled ligands were generated in high purity and specific...... 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-12-15

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

  19. 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

  20. Accurate assessment of long-term nephrotoxicity after peptide receptor radionuclide therapy with 177Lu-octreotate

    International Nuclear Information System (INIS)

    Sabet, Amir; Ezziddin, Khaled; Reichman, Karl; Haslerud, Torjan; Ahmadzadehfar, Hojjat; Biersack, Hans-Juergen; Ezziddin, Samer; Pape, Ulrich-Frank; Nagarajah, James

    2014-01-01

    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 99m Tc-diethylenetriaminepentaacetic acid (DTPA) clearance data of 74 consecutive patients with gastroenteropancreatic neuroendocrine tumours (GEP NET) undergoing PRRT with 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 99m Tc-DTPA clearance versus serum creatinine. The alteration in GFR differed widely among the patients (mean -2.1 ± 13.1 ml/min/m 2 per year, relative yearly reduction -1.8 ± 18.9 %). Fifteen patients (21 %) experienced a mild (2-10 ml/min/m 2 per year) and 16 patients (22 %) a significant (>10 ml/min/m 2 per year) decline of GFR following PRRT. However, 11 patients (15 %) showed an increase of >10 ml/min/m 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 patients. None of the investigated

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

    International Nuclear Information System (INIS)

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

    2009-01-01

    Adequate dosimetry is mandatory for effective and safe peptide receptor radionuclide therapy (PRRT). Besides the kidneys, the bone marrow is a potentially dose-limiting organ. The radiation dose to the bone marrow is usually calculated according to the MIRD scheme, where the accumulated activity in the bone marrow is calculated from the accumulated radioactivity of the radiopharmaceutical in the blood. This may underestimate the absorbed dose since stem cells express somatostatin receptors. We verified the blood-based method by comparing the activity in the blood with the radioactivity in bone marrow aspirates. Also, we evaluated the absorbed cross-dose from the source organs (liver, spleen, kidneys and blood), tumours and the so-called ''remainder of the body'' to the bone marrow. Bone marrow aspirates were drawn in 15 patients after treatment with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate. Radioactivity in the bone marrow was compared with radioactivity in the blood drawn simultaneously. The nucleated cell fraction was isolated from the bone marrow aspirate and radioactivity was measured. The absorbed dose to the bone marrow was calculated. The results were correlated to the change in platelet counts 6 weeks after treatment. A strong linear correlation and high agreement between the measured radioactivities in the bone marrow aspirates and in the blood was found (r=0.914, p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate, the radioactivity concentration in the bone marrow is identical to that in the blood; (2) There is no significant binding of the radiopharmaceutical to bone marrow precursor stem cells; (3) The contribution of the cross dose from source organs and tumours to the bone marrow dose is significant; and (4) There is considerable variation in bone marrow absorbed dose between patients. These findings imply that for individual dose optimization, individual calculation of the bone marrow absorbed dose is necessary. (orig.)

  2. Targeted radionuclide therapy with RAFT-RGD radiolabelled with {sup 90}Y or {sup 177}Lu in a mouse model of αvβ3-expressing tumours

    Energy Technology Data Exchange (ETDEWEB)

    Bozon-Petitprin, A.; Bacot, S.; Ahmadi, M.; Marti-Batlle, D.; Perret, P.; Broisat, A.; Riou, L.M. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); Gauchez, A.S.; Bourre, J.C.; Fagret, D.; Vuillez, J.P. [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); CHRU Grenoble, Hopital Michallon, Service de Medecine Nucleaire, Grenoble (France); Claron, M.; Boturyn, D. [CNRS, UMR 5250, Departement de Chimie Moleculaire, Grenoble (France); Ghezzi, Catherine [INSERM, U1039, Grenoble (France); Universite de Grenoble, UMR-S1039, Grenoble (France); INSERM U1039, Radiopharmaceutiques biocliniques, Batiment Jean Roget, Domaine de la Merci, Faculte de Medecine, La Tronche (France)

    2014-08-28

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK]){sub 4} (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β{sup -} emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with {sup 90}Y-RAFT-RGD or {sup 177}Lu-RAFT-RGD and {sup 90}Y-RAFT-RAD or {sup 177}Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of {sup 90}Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of {sup 177}Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of {sup 90}Y-RAFT-RAD or 37 MBq of {sup 177}Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of {sup 90}Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. {sup 90}Y-RAFT-RGD and {sup 177}Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy. (orig.)

  3. Targeted radionuclide therapy with RAFT-RGD radiolabelled with (90)Y or (177)Lu in a mouse model of αvβ3-expressing tumours.

    Science.gov (United States)

    Bozon-Petitprin, A; Bacot, S; Gauchez, A S; Ahmadi, M; Bourre, J C; Marti-Batlle, D; Perret, P; Broisat, A; Riou, L M; Claron, M; Boturyn, D; Fagret, D; Ghezzi, Catherine; Vuillez, J P

    2015-02-01

    The αvβ3 integrin plays an important role in tumour-induced angiogenesis, tumour proliferation, survival and metastasis. The tetrameric RGD-based peptide, regioselectively addressable functionalized template-(cyclo-[RGDfK])4 (RAFT-RGD), specifically targets the αvβ3 integrin in vitro and in vivo. The aim of this study was to evaluate the therapeutic potential of RAFT-RGD radiolabelled with β(-) emitters in a nude mouse model of αvβ3 integrin-expressing tumours. Biodistribution and SPECT/CT imaging studies were performed after injection of (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD in nude mice subcutaneously xenografted with αvβ3 integrin-expressing U-87 MG cells. Experimental targeted radionuclide therapy with (90)Y-RAFT-RGD or (177)Lu-RAFT-RGD and (90)Y-RAFT-RAD or (177)Lu-RAFT-RAD (nonspecific controls) was evaluated by intravenous injection of the radionuclides into mice bearing αvβ3 integrin-expressing U-87 MG tumours of different sizes (small or large) or bearing TS/A-pc tumours that do not express αvβ3. Tumour volume doubling time was used to evaluate the efficacy of each treatment. Injection of 37 MBq of (90)Y-RAFT-RGD into mice with large αvβ3-positive tumours or 37 MBq of (177)Lu-RAFT-RGD into mice with small αvβ3-positive tumours caused significant growth delays compared to mice treated with 37 MBq of (90)Y-RAFT-RAD or 37 MBq of (177)Lu-RAFT-RAD or untreated mice. In contrast, injection of 30 MBq of (90)Y-RAFT-RGD had no effect on the growth of αvβ3-negative tumours. (90)Y-RAFT-RGD and (177)Lu-RAFT-RGD are potent agents targeting αvβ3-expressing tumours for internal targeted radiotherapy.

  4. 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

  5. Peptide receptor radionuclide therapy with 177Lu-DOTA-octreotate: dosimetry, nephrotoxicity, and the effect of hematological toxicity on survival.

    Science.gov (United States)

    Löser, Anastassia; Schwarzenböck, Sarah M; Heuschkel, Martin; Willenberg, Holger S; Krause, Bernd J; Kurth, Jens

    2018-03-01

    Peptide receptor radionuclide therapy (PRRT) with lutetium-177 (Lu)-DOTATATE is regarded as a safe treatment option with promising results for patients with neuroendocrine neoplasia (NEN). We aimed to study the absorbed organ and tumor doses, the renal and hematological toxicity as well as their mutual interaction. Another aim was the identification of adverse effects as possible predictors which may affect survival. A total of 30 (14 female and 16 male) patients with inoperable/metastatic NEN were treated with 7.4 GBq of Lu-DOTATATE. Occurrence of renal and hematological toxicity wasretrospectively studied. Morever, we examined the effects of hematological toxicity on survival after Lu-DOTATATE-PRRT. In 49 treatment cycles, the mean absorbed dose to the kidneys was 5.13±2.12, 4.49±2.49 Gy to the liver, and 14.44±8.97 Gy to the spleen, whereas tumor lesions absorbed a mean dose of 31.43±36.86 Gy. Comparing different localizations of metastases, no significant differences in absorbed dose were observed. Clinical response status revealed regressive disease in 47.6%, stable disease in 38.1%, and progressive disease in 14.3% of cases (n=21). Biochemically, 81.3% of patients showed reduced serotonin values (n=16; P<0.05) following Lu-DOTATATE-PRRT. No severe subacute renal or hematological toxicity occurred (one Common Terminology Criteria for Adverse Events-grade 3 for thrombocytopenia and another one for leukocytopenia). No statistically significant relation between baseline kidney function and post-therapeutic hematological changes was identified. The findings indicate that Lu-DOTATATE-PRRT is a safe and effective treatment method for patients with NEN. Moreover, these data strongly suggest that hematological parameters may affect survival so a further re-evaluation in prospective studies is warranted.

  6. 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.)

  7. 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)

    Persson, Morten; Rasmussen, Palle; Madsen, Jacob; Ploug, Michael; Kjaer, Andreas

    2012-01-01

    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 64 Cu and 177 Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29 cells were inoculated in Nude mice and treated with 177 Lu-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 177 Lu-labeled non-binding control peptide and one receiving vehicle. All animals were treated day 0 and 7. A parallel 18 F-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 177 Lu-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 64 Cu-DOTA-AE105. Subsequently, these xenograft transplants were locally irradiated using 177 Lu-DOTA-AE105, where a significant effect on tumor size and the number of uPAR-positive cells in the tumor was found (p 18 F-FLT PET/CT imaging study revealed a significant correlation between 18 F-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

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

    DEFF Research Database (Denmark)

    Persson, Morten; Rasmussen, Palle; Madsen, Jacob

    2012-01-01

    -of-concept for a theranostic approach as treatment modality in a human xenograft colorectal cancer model. MethodsA DOTA-conjugated 9-mer high affinity uPAR binding peptide (DOTA-AE105) was radiolabeled with 64Cu and 177Lu, for PET imaging and targeted radionuclide therapy study, respectively. Human uPAR-positive CRC HT-29...... for the first time the in vivo efficacy of an uPAR-targeted radionuclide therapeutic intervention on both tumor size and its content of uPAR expressing cells thus setting the stage for future translation into clinical use. © 2012 Elsevier Inc. All rights reserved....

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

    International Nuclear Information System (INIS)

    Puranik, Ameya D.; Kulkarni, Harshad R.; Singh, Aviral; Baum, Richard P.

    2015-01-01

    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 90 Y/ 177 Lu-labelled peptides after positive confirmation of SSTR expression on 68 Ga-DOTATOC PET/CT. All patients received two to four courses of PRRT. Subsequent serial imaging with 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 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 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 distant spread. Though these

  10. Evaluation of cytotoxic and tumor targeting capability of (177)Lu-DOTATATE-nanoparticles: a trailblazing strategy in peptide receptor radionuclide therapy.

    Science.gov (United States)

    Arora, Geetanjali; Dubey, Priyanka; Shukla, Jaya; Ghosh, Sourabh; Bandopadhyaya, Gurupad

    2016-06-01

    We propose an innovative strategy of nanoparticle-mediated-peptide receptor radionuclide therapy (PRRT) employing PLGA-nanoparticles together with anti-β-hCG antibodies that can protect kidneys from radiation damage while simultaneously enhancing its tumor targeting and cytotoxic ability for somatostatin receptor (SSR) positive tumors. PEG-coated-(177)Lu-DOTATATE-PLGA-nanoparticles (PEG-LuD-NP) were formulated and characterized. In vitro toxicity of these particles was tested on human glioblastoma cell line U87MG over a radiation dose range of 19-78 Gy, using MTT assay and flow cytometry. To further enhance cytotoxicity and test the feasibility of active tumor targeting, apoptosis-inducing anti-β-hCG monoclonal antibodies were employed in vitro, after confirming expression of β-hCG on U87MG. In vivo tumor targeting ability of these particles, in comparison to uncoated particles and un-encapsulated (177)Lu-DOTATATE, was assessed by intravenous administration in tumor-induced wistar rats. Rats were first imaged in a gamma camera followed by euthanasia for organ extraction and counting in gamma counter. The particles were spherical in shape with mean diameter of 300 nm. Highest cytotoxicity that could be achieved with PEG-LuD-NP, on radio-resistant U87MG cells, was 35.8 % due to complex cellular response triggered by ionizing radiation. Interestingly, synergistic action of antibodies and PEG-LuD-NP doubled the cytotoxicity (80 %). PEG-LuD-NP showed the highest tumor uptake (4.3 ± 0.46 % ID/g) as compared to (177)Lu-DOTATATE (3.5 ± 0.31 %) and uncoated-(177)Lu-DOTATATE-nanoparticles (3.4 ± 0.35 %) in tumor-inoculated wistar rats (p targeting SSR positive tumors for enhanced cytoxicity and reduced renal radiation dose associated with conventional PRRT. To our knowledge of literature, this is the first study to establish in vitro and in vivo efficacy profile of nanoparticles in PRRT providing a stepping-stone for undergoing and future research

  11. Preclinical Evaluation of a Novel 177Lu- Radiopharmaceutical Based on Bombesin Structure for Prostate Tumor Diagnosis and Radionuclide Therapy

    International Nuclear Information System (INIS)

    Pujatti, P.B.; Santos, J.S.; Mengatti, J.; Araujo, E.B. de; Suzuki, M.F.; Soares, C.R.J.

    2009-01-01

    evaluation of cold bombesin derivative effect in PC-3 cells proliferation by MTS assay. Bombesin derivative (20□g) was successfully radiolabeled with 97.5 MBq of 177 Lu at 90 deg. C for 30 minutes and pH 4.5. This mixture kept stable for more than 96 hours at 4 deg. C and 1 hour in fresh human serum. Investigations in Balb-c mice showed a multicompartimental model of biodistribution, with fast blood clearance, rapid excretion, performed mainly by renal pathway, low abdominal accumulation in pancreas and intestines and low retention in organism, with 90% of total radioactivity excreted in the first 4 hours p.i. The studies in Nude mice bearing human prostate (PC-3) tumor showed that the radiopeptide exhibited significant target to tumor cells. Higher tumor uptake was observed at 1 hour post injection (0.88 + 0.11% ID/g and 4.38 + 0.54% of the radioactivity presented in organism) and showed to be specific in vivo. The pre-injection of unlabeled peptide reduced 88% of labeled peptide target to tumor cells. Moreover, tumor uptake allowed tumor detection by scintigraphy imaging, especially one hour post injection, but also 4 hours p.i. In addition, the studied bombesin derivative did not present proliferative or citotoxic effect to PC-3 cells in vitro and can be characterized as a weak agonist or antagonist of bombesin receptors. The results of this work showed that this novel radiopharmaceutical based on bombesin structure is promising for applications in prostate tumor detection and treatment. (author)

  12. 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

  13. PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues

    Science.gov (United States)

    2012-01-01

    growth. The therapeutic efficacy was highest for the PEGylated derivative of high specific activity administered in two fractions (2 × 20 MBq = 40 MBq) at day 0 and day 7 (73% tumour growth inhibition, 3 weeks after therapy). Conclusions PEGylation and increasing the specific activity enhance the pharmacokinetic properties of a 177Lu-labelled BN-based radiopharmaceutical and provide a protocol for targeted radionuclide therapy with a beneficial anti-tumour effectiveness and a favourable risk-profile at the same time. PMID:22681935

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

    International Nuclear Information System (INIS)

    Sainz-Esteban, Aurora; Carril, Jose Manuel; Prasad, Vikas; Schuchardt, Christiane; Zachert, Carolin; Baum, Richard P.

    2012-01-01

    The aim of the study was to compare sequential 177 Lu-DOTA-TATE planar scans ( 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 68 Ga-DOTA-TATE positron emission tomography (PET)/CT ( 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 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE imaging within 7.9 ± 7.5 days between the two examinations. 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 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 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 68 Ga-DOTA-TATE positive and 177 Lu-DOTA-TATE negative, whereas 9 were 68 Ga-DOTA-TATE negative and 177 Lu-DOTA-TATE positive. The sensitivity, positive predictive value and accuracy for 177 Lu-DOTA-TATE as compared to 68 Ga-DOTA-TATE were 91, 97 and 88%, respectively. Significantly more lesions were seen on the delayed (72 h) 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 max ). However, concordant liver lesions with a score from 1 to 3 in the 72-h 177 Lu-DOTA-TATE scan had a lower SUV max

  15. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-15

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

  17. Peptide Receptor Radionuclide Therapy with 177Lu-DOTATATE for Metastatic Neuroendocrine Tumor Occurring in Association with Multiple Endocrine Neoplasia Type 1 and Cushing's Syndrome.

    Science.gov (United States)

    Naik, Chinna; Basu, Sandip

    2017-01-01

    Neuroendocrine tumor (NET) occurring in association with other endocrine syndromes forms a distinct entity. The aim was to assess the therapy response profile of the routine peptide receptor radionuclide therapy (PRRT) in this relatively uncommon but clinically challenging subgroup of patients. A retrospective analysis was undertaken from the case records from those who were treated with 177 Lu-DOTATATE for metastatic NET. In addition to assessing the therapeutic efficacy, emphasis was also given to study lesional sites and scan pattern. A total of 5 cases were found: In this series of five cases, four belonged to multiple endocrine neoplasia type 1 (MEN1) syndrome; in these four MEN1 syndrome patients, the primary site of NET was thymic region ( n = 1), duodenum ( n = 1), and pancreas ( n = 2). The fifth case was of Cushing's syndrome with the primary site of NET in the thymus. A good symptomatic response was observed in all MEN1 syndrome cases (100%) and progression of symptoms in the patient with Cushing's syndrome. The biochemical response (assessed by measurement of tumor marker serum chromogranin A) demonstrated very good partial response (defined by more than 75% reduction of tumor marker) in 2 MEN1 cases and Cushing's syndrome, good partial response (25-75% reduction of tumor marker) in the remaining 2 MEN1 cases. Scan wise (assessed by technetium [ 99m Tc]-hydrazinonicotinamide [HYNIC]-tektrotyd [TOC]/ 68 Ga-DOTA-NOC/TATE positron emission tomography-computed tomography [PET-CT] and fluorodeoxyglucose [FDG] PET-CT) partial response was observed in 3 MEN1 cases, stable disease was noted in one MEN1 case and disease progression was noted in the patient with Cushing's syndrome. The change in FDG uptake was found to be an important sensitive scan parameter in the treatment evaluation of NETs compared to somatostatin receptor-based imaging in the cases with low MiB1 index. In our series, good palliative response to 177 Lu-DOTA-octreotate (DOTATATE) PRRT was

  18. 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.)

  19. In vitro characterization of 177Lu-radiolabelled chimeric anti-CD20 monoclonal antibody and a preliminary dosimetry study

    International Nuclear Information System (INIS)

    Forrer, Flavio; Mueller-Brand, Jan; Chen, Jianhua; Fani, Melpomeni; Powell, Pia; Maecke, Helmut R.; Lohri, Andreas; Moldenhauer, Gerhard

    2009-01-01

    131 I- and 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 ( 177 Lu or 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 5 times excess of diethylenetriaminepentaacetic acid (DTPA, 37 C, 7 days). Two patients with relapsed NHL were treated with 740 MBq/m 2 body surface 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 177 Lu-DOTA-rituximab was tolerated well. Our results show that DOTA-rituximab (4:1) can be labelled with 177 Lu with sufficient stability while the immunoconjugate retains its immunoreactivity. 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.)

  20. 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

  1. Absorbed dose profiles for 32P, 90Y, 188Re, 177Lu, 51Cr, 153Sm and 169Er: radionuclides used in radiosynoviortheses treatment

    International Nuclear Information System (INIS)

    Torres, M.; Ayra, E.; Albuerne, O.; Delgado, M.

    2008-01-01

    The remarkable advances in the design and synthesis of radiopharmaceuticals has created the opportunity of generating new agents for the treatment of radiosynoviortheses (RSV) which exhibit a minimum leakage from the synovial joint reducing, this way, the non desired absorbed doses to non target organs such as liver, spleen, kidney. Nowadays, the variety of beta emitters used in RSV ranges between 0.34 MeV - 0.33 mm penetration in tissue ( 169 Er) and 2.27 MeV - 3.6 mm penetration in tissue ( 90 Y). The half life of these isotopes goes from 2.3 hours ( 165 Dy) to 27.8 days ( 51 Cr). The selection criterion on which radionuclide should be used, in modern clinics, depends on which joints are to be treated. Thus, the smaller the joint, the lowest should be the energy of the beta emitted and the penetration in soft tissue of these particles. This leads to the use of fixed radionuclides and doses for each kind of joint. In the Isotopes Centre, we've been carrying on studies for the development of radiopharmaceuticals for the radiosynoviortheses treatment and focused our attention in the following radionuclides: 32 P, 90 Y, 188 Re, 177 Lu, 51 Cr, 153 Sm and 169 Er. The main objective of this paper was to obtain the absorbed dose profiles for radionuclides of frequent or potential use in radiosynoviortheses. These profiles reveal the absorbed dose imparted per unit activity of injected radionuclide (Gy/h*MBq) in the synovial membrane and the articular cartilage. The researched radionuclides were those previously mentioned. Also were calculated the therapeutic range of each radionuclides in synovial tissue. The therapeutic range is defined as the deepness at which the absorbed dose equals the 10 % of the maximum dose deposited in the synovial surface. This range determines the synovial thickness that can be sufficiently irradiated and thus successfully treated. The synovial membrane model consisted on a cylinder with the source uniformly distributed in its volume. This

  2. 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

  3. Labelling of 90Y- and 177Lu-DOTA-Bioconjugates for Targeted Radionuclide Therapy: A Comparison among Manual, Semiautomated, and Fully Automated Synthesis

    Directory of Open Access Journals (Sweden)

    Michele Iori

    2017-01-01

    Full Text Available In spite of the hazard due to the radiation exposure, preparation of 90Y- and 177Lu-labelled radiopharmaceuticals is still mainly performed using manual procedures. In the present study the performance of a commercial automatic synthesizer based on disposable cassettes for the labelling of 177Lu- and 90Y-DOTA-conjugated biomolecules (namely, DOTATOC and PSMA-617 was evaluated and compared to a manual and a semiautomated approach. The dose exposure of the operators was evaluated as well. More than 300 clinical preparations of both 90Y- and 177Lu-labelled radiopharmaceuticals have been performed using the three different methods. The mean radiochemical yields for 90Y-DOTATOC were 96.2±4.9%, 90.3±5.6%, and 82.0±8.4%, while for 177Lu-DOTATOC they were 98.3%  ± 0.6, 90.8%  ± 8.3, and 83.1±5.7% when manual, semiautomated, and automated approaches were used, respectively. The mean doses on the whole hands for yttrium-90 preparations were 0.15±0.4 mSv/GBq, 0.04±0.1 mSv/GBq, and 0.11±0.3 mSv/GBq for manual, semiautomated, and automated synthesis, respectively, and for lutetium-177 preparations, they were 0.02±0.008 mSv/GBq, 0.01±0.03 mSv/GBq, and 0.01±0.02 mSv/GBq, respectively. In conclusion, the automated approach guaranteed reliable and reproducible preparations of pharmaceutical grade therapeutic radiopharmaceuticals in a decent RCY. The radiation exposure of the operators remained comparable to the manual approach mainly due to the fact that a dedicated shielding was still not available for the system.

  4. Alternative method to determine Specific Activity of (177)Lu by HPLC.

    Science.gov (United States)

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

    2015-01-01

    Peptide Receptor Radionuclide Therapy (PRRT) with (177)Lu-DOTA-peptides requires (177)Lu with high specific activity (SA) and values >740 GBq (177)Lu per mg Lu to maximise the atom% of (177)Lu over total Lu. Vendors provide SA values which are based on activity and mass of the target, whereas due to "burn-up" of target, these SA values are not accurate. For a radiochemist the SA of (177)Lu is of interest prior to radiolabeling. An alternative method to determine SA was developed by HPLC, which includes a metal titration of a known amount of DOTA-peptide with a known amount of activity ((177)Lu), and a unknown amount of metal ((177+nat)Lu). Based on an HPLC separation of radiometal-DOTA-peptide and DOTA-peptide, and the concordant ratio of these components the metal content ((177+nat)Lu) can be calculated, and eventually the SA of (177)Lu can be accurately determined. These experimentally determined SA values exceeded the estimated values provided by vendors by 27 ± 16%, (range 6-73 %). The deviation of SA values for samples from the same Lu batch was <2% (n ≥ 10). the SA of (177)Lu is apparently often higher as stated by vendors in comparison to the experimentally determined actual values. For this reason, the SA of (177)Lu-DOTA-TATE and other Lu-DOTA-peptides could be increased accordingly.

  5. Dosimetric Studies in Normal Mice of 177Lu-DOTA-SP and 177Lu-DOTA-His2-MG

    International Nuclear Information System (INIS)

    Puerta Yepes, N.; Rojo, A.M.; Lopez Bularte, A.C.; Nevares, N.; Zapata, M.; Perez, J.H.; Crudo, J.

    2010-01-01

    DOTA-Substance-P (SP) and DOTA-minigastrin (His2-MG) labeled with 177 Lu could be used in peptide receptor radionuclide therapy (PRRT) for treatment of various tumour species. Biodistribution studies of both radiopharmaceuticals in normal mice were performed at different times. Absorbed doses in mouse organs were estimated and extrapolated to humans. Dosimetric calculations showed that kidneys received the highest dose, for both radiopharmaceuticals. The Maximum Tolerated Activity (MTA) of 177 Lu-DOTA-SP that can be administered without kidney toxicity are 414 and 422 MBq/kg for the standard adult man and woman, respectively. In the same way, the MTA of 177 Lu-DOTA-His2-MG are 488 and 518 MBq/kg for the standard adult man and woman, respectively. (authors)

  6. 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.)

  7. 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.)

  8. 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.

  9. Primary standardization of a {sup 177}Lu solution; Padronizacao primaria de uma solucao de {sup 177}Lu

    Energy Technology Data Exchange (ETDEWEB)

    Iwahara, Akira; Silva, Carlos Jose da; Tauhata, Luiz; Oliveira, Estela Maria de, E-mail: iwahara@ird.gov.b, E-mail: carlos@ird.gov.b, E-mail: tauhata@ird.gov.b, E-mail: estela@ird.gov.b [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil); Rezende, Eduarda Alexandre, E-mail: eduarda@ird.gov.b [Centro Federal de Educacao Tecnologica de Quimica (CEFET), Nilopolis, RJ (Brazil)

    2009-07-01

    For the purpose to make available reliable standards of {sup 177}Lu to the users and producers, a radionuclide solution was standardized using the primary methods of coincidence 4{pi}{beta}(PC)-{gamma}(NaI(Tl)) and of 4{pi}{beta}(LS)-{gamma}(NaI(Tl)). The results presented a convergence in the range of evaluated uncertainties. The standard uncertainties were of the 0.50 and 0.74% for the anticoincidence and coincidence respectively

  10. [{sup 177}Lu]pertuzumab: experimental studies on targeting of HER-2 positive tumour cells

    Energy Technology Data Exchange (ETDEWEB)

    Persson, Mikael; Gedda, Lars [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Uppsala University, Experimental Urology, Rudbeck Laboratory, Uppsala (Sweden); Tolmachev, Vladimir; Andersson, Karl; Carlsson, Joergen [Uppsala University, Biomedical Radiation Sciences, Rudbeck Laboratory, Uppsala (Sweden); Sandstroem, Mattias [Uppsala University, Medical Radiation Physics, Uppsala University Hospital, Uppsala (Sweden)

    2005-12-01

    The new antibody pertuzumab (Omnitarg) targets the dimerisation subdomain of HER-2. The purpose of this study was to analyse whether pertuzumab retains HER-2 targeting capacity after labelling with the therapeutically interesting beta emitter {sup 177}Lu and to make initial characterisations in vitro and in vivo. Pertuzumab was conjugated with isothiocyanate-benzyl-CHX-A{sup ''}-DTPA and chelated to {sup 177}Lu. Immunoreactivity, affinity, cellular retention and internalisation were analysed using SKOV-3 cells. The affinity of non-radioactive pertuzumab was measured using a surface plasmon resonance biosensor. In vivo targeting and specific binding were assessed in Balb/c (nu/nu) mice carrying SKOV-3 xenografts. The biodistribution of {sup 177}Lu was determined 1, 3 and 7 days after [{sup 177}Lu]pertuzumab administration. Gamma camera images were taken after 3 days. The immunoreactivity of [{sup 177}Lu]pertuzumab was 85.8{+-}1.3%. The affinity of non-radioactive pertuzumab was 1.8{+-}1.1 nM, and that of [{sup 177}Lu]pertuzumab, 4.1{+-}0.7 nM. The cellular retention after 5 h pre-incubation was 90{+-}2% at 20 h. The targeting was HER-2 specific both in vitro and in vivo, since excess amounts of non-labelled antibody inhibited the uptake of labelled antibody (p<0.0001 and p<0.01, respectively). The biodistribution and gamma camera images of {sup 177}Lu showed extensive tumour uptake. Normal tissues had a surprisingly low uptake. Pertuzumab was efficiently labelled with {sup 177}Lu and showed good intracellular retention and HER-2 specific binding both in vitro and in vivo. The gamma camera images and the biodistribution study gave excellent tumour targeting results. Thus, [{sup 177}Lu]pertuzumab is of interest for further studies aimed at radionuclide therapy. (orig.)

  11. Additional lesions detected in therapeutic scans with 177Lu-DOTATATE reflect higher affinity of 177Lu-DOTATATE for somatostatin receptors.

    Science.gov (United States)

    Mirzaei, Siroos; Bastati, Brigitte; Lipp, Rainer W; Knoll, Peter; Zojer, Niklas; Ludwig, Heinz

    2011-01-01

    Peptide receptor-targeted radionuclide therapy (PRRT) of somatostatin receptor (SR)-expressing neuroendocrine tumors (NETs) has become an established therapeutic option in patients with advanced NETs. The aim of this study was to compare the lesion detection rate of (99m)Tc-EDDA/HYNIC-TOC, a newly developed tracer for NET imaging, with (177)Lu-DOTATATE used for PRRT. 8 patients (4 women, 4 men, age range 46-76 years) with histologically proven NETs, who showed high SR loads by (99m)Tc-EDDA/HYNIC-TOC scintigraphy, were treated with (177)Lu-DOTATATE. After treatment, all patients were subjected to whole-body scintigraphy with additional low-dose single-photon emission computed tomography (SPECT-CT) of the chest and abdomen. All patients demonstrated (177)Lu-DOTATATE accumulation in all lesions previously detected by (99m)Tc- EDDA/HYNIC-TOC scintigraphy. Three patients showed additional lesions in the liver and lungs. SPECT-CT after (177)Lu-DOTATATE therapy may be helpful in detecting additional lesions not seen using (99m)Tc-EDDA/HYNIC-TOC. This could reflect the broader affinity of (177)Lu-DOTATATE for SRs compared with (99m)Tc-EDDA/HYNIC-TOC. Copyright © 2011 S. Karger AG, Basel.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  14. An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications

    International Nuclear Information System (INIS)

    Chakravarty, Rubel; Das, Tapas; Dash, Ashutosh; Venkatesh, Meera

    2010-01-01

    Introduction: A novel two-step separation process for the production of no-carrier-added (NCA) 177 Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. Methods: A two-cycle electrolysis procedure was adopted for separation of 177 Lu from 177 Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of 177 Lu. The first electrolysis was performed for 50 min in the 177 Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of 177 Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of 177 Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe 1 -Tyr 3 -octreotate(DOTA-TATE) with 177 Lu. Results: This process could provide NCA 177 Lu with >99.99% radionuclidic purity and an overall separation yield of ∼99% was achieved within 3-4 h. The Hg content in the product was determined to be 98% was obtained with DOTA-TATE under the optimized reaction conditions. Conclusions: An efficient strategy for the separation of NCA 177 Lu, suitable for biomedical applications, has been developed.

  15. An electro-amalgamation approach to isolate no-carrier-added 177Lu from neutron irradiated Yb for biomedical applications.

    Science.gov (United States)

    Chakravarty, Rubel; Das, Tapas; Dash, Ashutosh; Venkatesh, Meera

    2010-10-01

    A novel two-step separation process for the production of no-carrier-added (NCA) (177)Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. A two-cycle electrolysis procedure was adopted for separation of (177)Lu from (177)Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of (177)Lu. The first electrolysis was performed for 50 min in the (177)Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of (177)Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of (177)Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe(1)-Tyr(3)-octreotate(DOTA-TATE) with (177)Lu. This process could provide NCA (177)Lu with >99.99% radionuclidic purity and an overall separation yield of ∼99% was achieved within 3-4 h. The Hg content in the product was determined to be 98% was obtained with DOTA-TATE under the optimized reaction conditions. An efficient strategy for the separation of NCA (177)Lu, suitable for biomedical applications, has been developed. Copyright © 2010 Elsevier Inc. All rights reserved.

  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. Reducing renal uptake of 9Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    International Nuclear Information System (INIS)

    Miao Yubin; Fisher, Darrell R.; Quinn, Thomas P.

    2006-01-01

    Objective: The purpose of this study was to improve the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-[1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys 3,4,1 , D-Phe 7 , Arg 11 ]α-melanocyte stimulating hormone 3-13 {DOTA-Re(Arg 11 )CCMSH} through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. Methods: A new peptide of DOTA-Re(Glu 2 , Arg 11 )CCMSH was designed, synthesized and labeled with 9 Y and 177 Lu. Pharmacokinetics of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was determined in B16/F1 murine melanoma-bearing C57 mice. Results: 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH exhibited significantly (P 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The renal uptake values of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH were 28.16% and 28.81% of those of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH displayed higher tumor-to-kidney uptake ratios than 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH at 30 min and at 2, 4 and 24 h after dose administration. The tumor-to-kidney uptake ratio of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH was 2.28 and 1.69 times of 9 Y- and 177 Lu-DOTA-Re(Arg 11 )CCMSH, respectively, at 4 h postinjection. The 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH activity accumulation was low in normal organs except for kidney. Conclusions: Coupling a negatively charged amino acid (Glu) to the CCMSH peptide sequence dramatically reduced the renal uptake values and increased the tumor-to-kidney uptake ratios of 9 Y- and 177 Lu-DOTA-Re(Glu 2 , Arg 11 )CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma

  18. Somatostatin-based Radiopeptide Therapy with [177Lu-DOTA]-TOC versus [90Y-DOTA]-TOC in Neuroendocrine Tumors

    OpenAIRE

    Romer A Seiler D Marincek N Brunner P Koller MT Ng QK Maecke HR Muller-Brand J Rochlitz C B

    2014-01-01

    PURPOSE: Somatostatin based radiopeptide treatment is generally performed using the ß emitting radionuclides (90)Y or (177)Lu. The present study aimed at comparing benefits and harms of both therapeutic approaches. METHODS: In a comparative cohort study patients with advanced neuroendocrine tumours underwent repeated cycles of [(90)Y DOTA] TOC or [(177)Lu DOTA] TOC until progression of disease or permanent adverse events. Multivariable Cox regression and competing risks regression were emplo...

  19. 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.

  20. Targeting angiogenesis for radioimmunotherapy with a {sup 177}Lu-labeled antibody

    Energy Technology Data Exchange (ETDEWEB)

    Ehlerding, Emily B.; Hernandez, Reinier [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); Lacognata, Saige; Jiang, Dawei [University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); Ferreira, Carolina A. [University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); Goel, Shreya [University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States); Jeffery, Justin J. [University of Wisconsin - Madison, Small Animal Imaging Facility, Madison, WI (United States); Theuer, Charles P. [TRACON Pharmaceuticals, Inc., San Diego, CA (United States); Cai, Weibo [University of Wisconsin - Madison, Department of Medical Physics, Madison, WI (United States); University of Wisconsin - Madison, Department of Radiology, Madison, WI (United States); University of Wisconsin - Madison, Department of Biomedical Engineering, Madison, WI (United States); University of Wisconsin - Madison, Department of Materials Science and Engineering, Madison, WI (United States)

    2018-01-15

    Increased angiogenesis is a marker of aggressiveness in many cancers. Targeted radionuclide therapy of these cancers with angiogenesis-targeting agents may curtail this increased blood vessel formation and slow the growth of tumors, both primary and metastatic. CD105, or endoglin, has a primary role in angiogenesis in a number of cancers, making this a widely applicable target for targeted radioimmunotherapy. The anti-CD105 antibody, TRC105 (TRACON Pharmaceuticals), was conjugated with DTPA for radiolabeling with {sup 177}Lu (t{sub 1/2} 6.65 days). Balb/c mice were implanted with 4T1 mammary carcinoma cells, and five study groups were used: {sup 177}Lu only, TRC105 only, {sup 177}Lu-DTPA-IgG (a nonspecific antibody), {sup 177}Lu-DTPA-TRC105 low-dose, and {sup 177}Lu-DTPA-TRC105 high-dose. Toxicity of the agent was monitored by body weight measurements and analysis of blood markers. Biodistribution studies of {sup 177}Lu-DTPA-TRC105 were also performed at 1 and 7 days after injection. Ex vivo histology studies of various tissues were conducted at 1, 7, and 30 days after injection of high-dose {sup 177}Lu-DTPA-TRC105. Biodistribution studies indicated steady uptake of {sup 177}Lu-DTPA-TRC105 in 4T1 tumors between 1 and 7 days after injection (14.3 ± 2.3%ID/g and 11.6 ± 6.1%ID/g, respectively; n = 3) and gradual clearance from other organs. Significant inhibition of tumor growth was observed in the high-dose group, with a corresponding significant increase in survival (p < 0.001, all groups). In most study groups (all except the nonspecific IgG group), the body weights of the mice did not decrease by more than 10%, indicating the safety of the injected agents. Serum alanine transaminase levels remained nearly constant indicating no damage to the liver (a primary clearance organ of the agent), and this was confirmed by ex vivo histological analyses. {sup 177}Lu-DTPA-TRC105, when administered at a sufficient dose, is able to curtail tumor growth and provide a

  1. Internal radiotherapy and dosimetric study for 111In/177Lu-pegylated liposomes conjugates in tumor-bearing mice

    International Nuclear Information System (INIS)

    Wang, H.-E.; Yu, H.-M.; Lu, Y.-C.; Heish, N.-N.; Tseng, Yun-Long; Huang, K.-L.; Chuang, K.-T.; Chen, Chin-Hsiung; Hwang, J.-J.; Lin, W.-J.; Wang, Shyh-Jen; Ting, G.; Whang-Peng, Jacqueline; Deng, W.-P.

    2006-01-01

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with 111 In/ 177 Lu-(oxine) 3 to afford 111 In/ 177 Lu-liposome. The stability of 111 In/ 177 Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111 In/ 177 Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of 111 In/ 177 Lu into liposomes was 95%. After incubation at 37 o C for 72 h in serum, more than 83% of radioactivity was still retained in the intact 111 In/ 177 Lu-liposomes. The biodistribution of 111 In-liposomes showed that the radioactivity in the blood decreased from 23.14±8.16%ID/g at 1 h to 0.02±0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of 177 Lu-liposomes. Scintigraphic imaging with 111 In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from 177 Lu-liposomes was 5.74x10 -5 Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes

  2. Production and Quality Control of 177Lu-Dotatate [177Lu-dota- try3]-Octreotate: Clinical Application

    International Nuclear Information System (INIS)

    Barboza, M.F. de; Herrerias, R.; Souza, A.A. de; Pereira, G.; Pires, J.A.; Fukumori, N.T.O.; Matsuda, M.M.N.; Almeida, E.V.; Mengatti, J.; Belfer, A.J.; Hilario, L.N.

    2009-01-01

    Introduction: Somatostatin receptors have been identified in different kinds of tumors such as neuroendocrine tumors and tumors of the central nervous system, breast, lung and lymphatic tissue making these receptors potential targets for radionuclide diagnostics and therapy. These observations have served as the biomolecular basis for the clinical use of radiolabeled somatostatin analogues which, at present, are of great interest in nuclear medicine for diagnostic and peptide receptor radionuclide therapy (PRRT) applications. There are only a few treatment modalities for metastasized neuroendocrine gastroenteropancreatic (GEP) tumors. Besides surgery, (chemo)-embolization, chemotherapy, and treatment with somatostatin (SST) analogs, peptide receptor radionuclide therapy (PRRT) offers therapeutic strategy, as the majority of GEP tumors possess somatostatin receptors (SSTRs). Somatostatin analogs featuring a DOTA-chelator can be radiolabeled with the β-emitters radioisotopes, Yttrium-90 ( 90 Y) and Lutetium-177 ( 177 Lu) for PRRT. Analogs frequently used for therapy are: [DOTA-Tyr 3 ]-octreotide and [DOTA-Tyr 3 ]octreotate. In the latter compound, the alcohol threoninol at the C-terminal of the octreotide has been replaced by the natural threonin amino acid. This alteration resulted in an analog: (Tyr 3 -octreotate), which showed increased affinity for sst2, compared to both [Tyr 3 ]-octreotide and [Phe 1 ]octreotide 'in-vitro' and 'in-vivo'. Clinical studies in patients with different SST-positives tumors proved advantages of [ 177 Lu- DOTA-Tr 3 ]-octreate for therapy. PRRT with radiolabeled somatostatin analogs was shown to be effective in patients with SST2-positive-size reduction, improving quality of life and survival. Objective: The aim of this work was to present the production and the quality control of 177 Lu-Tyr 3 ---octreotate, using DOTA (1,4,7,10-tetrazacyclododecane-N,N',N',N''-tetra acetic acid) as chelating agent at the Radiopharmacy Directory, IPEN

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

    International Nuclear Information System (INIS)

    Romer, A.; Seiler, D.; Brunner, P.; Ng, Q.K.T.; Mueller-Brand, J.; Marincek, N.; Walter, M.A.; Koller, M.T.; Maecke, H.R.; Rochlitz, C.; Briel, M.; Schindler, C.

    2014-01-01

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides 90 Y or 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 [ 90 Y-DOTA]-TOC or [ 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 [ 90 Y-DOTA]-TOC and 141 patients underwent 259 cycles of [ 177 Lu-DOTA]-TOC. The median survival after [ 177 Lu-DOTA]-TOC and after [ 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 [ 177 Lu-DOTA]-TOC over [ 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 [ 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 [ 177 Lu-DOTA]-TOC and [ 90 Y-DOTA]-TOC. Furthermore, [ 177 Lu-DOTA]-TOC was less haematotoxic than [ 90 Y-DOTA]-TOC. (orig.)

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

    Science.gov (United States)

    Romer, A; Seiler, D; Marincek, N; Brunner, P; Koller, M T; Ng, Q K T; Maecke, H R; Müller-Brand, J; Rochlitz, C; Briel, M; Schindler, C; Walter, M A

    2014-02-01

    Somatostatin-based radiopeptide treatment is generally performed using the β-emitting radionuclides (90)Y or (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 [(90)Y-DOTA]-TOC or [(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 [(90)Y-DOTA]-TOC and 141 patients underwent 259 cycles of [(177)Lu-DOTA]-TOC. The median survival after [(177)Lu-DOTA]-TOC and after [(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 [(177)Lu-DOTA]-TOC over [(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 [(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 [(177)Lu-DOTA]-TOC and [(90)Y-DOTA]-TOC. Furthermore, [(177)Lu-DOTA]-TOC was less haematotoxic than [(90)Y-DOTA]-TOC.

  5. Use of 82Br and 131I radionuclides in studies of goitrogenic effects of exogenous bromide

    International Nuclear Information System (INIS)

    Stanislav Pavelka

    2012-01-01

    The interference of excessive bromide intake with iodine metabolism in the rat was studied using 82 Br and 131 I radionuclides. Mainly lactating rat dams and their pups were used, in addition to adult male rats, in the present studies. Particularly, the influence of high bromide intake in lactating rat dams on the transfer of iodine and bromide to suckling young through breast milk was evaluated. The induction of hypothyroid status in the pups by high bromide intake in the mothers was proved unambiguously. Excessive bromide in lactating rat dams caused a marked decrease in plasma levels of thyroid hormones both, in the mothers and in their sucklings. The effects of an enhanced bromide intake on the thyroid function in relation to iodine status in the animals were also followed. Marked goitrogenic and thyrotoxic effects of excessive bromide in adult rats were significantly enhanced under the conditions of simultaneous iodine deficiency in the experimental animals. (author)

  6. An electro-amalgamation approach to isolate no-carrier-added {sup 177}Lu from neutron irradiated Yb for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Chakravarty, Rubel; Das, Tapas [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Dash, Ashutosh, E-mail: adash@barc.gov.i [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India); Venkatesh, Meera [Radiopharmaceuticals Division, Bhabha Atomic Research Centre, Mumbai 400085 (India)

    2010-10-15

    Introduction: A novel two-step separation process for the production of no-carrier-added (NCA) {sup 177}Lu from neutron irradiated Yb target through an electrochemical pathway employing mercury-pool cathode has been developed. Methods: A two-cycle electrolysis procedure was adopted for separation of {sup 177}Lu from {sup 177}Lu/Yb mixture in lithium citrate medium. The influence of different experimental parameters on the separation process was investigated and optimized for the quantitative deposition of Yb in presence of {sup 177}Lu. The first electrolysis was performed for 50 min in the {sup 177}Lu/Yb feed solution at pH 6 applying a potential of 8 V using platinum electrode as anode and mercury as the cathode. The second electrolysis was performed under the same conditions using fresh electrodes. The radionuclidic and chemical purity of {sup 177}Lu was determined by using gamma ray spectrometry and atomic absorption spectrometry. The suitability of {sup 177}Lu for biomedical applications was ascertained by labeling 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid D-Phe{sup 1}-Tyr{sup 3}-octreotate(DOTA-TATE) with {sup 177}Lu. Results: This process could provide NCA {sup 177}Lu with >99.99% radionuclidic purity and an overall separation yield of {approx}99% was achieved within 3-4 h. The Hg content in the product was determined to be <1 ppm. Radiolabeling yield of >98% was obtained with DOTA-TATE under the optimized reaction conditions. Conclusions: An efficient strategy for the separation of NCA {sup 177}Lu, suitable for biomedical applications, has been developed.

  7. Effects of therapy with [177Lu-DOTA0,Tyr3]octreotate on endocrine function

    International Nuclear Information System (INIS)

    Teunissen, Jaap J.M.; Kwekkeboom, Dik J.; Krenning, Eric P.; Jong, Frank H. de; Feelders, Richard A.; Aken, Maarten O. van; Herder, Wouter W. de; Rijke, Yolanda B. de

    2009-01-01

    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 [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 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 4 ) levels decreased (17.7 ± 0.4 to 15.6 ± 0.6 pmol/l, p 3 ) levels did not change. Reverse triiodothyronine (rT 3 ) levels decreased (0.38 ± 0.03 to 0.30 ± 0.01 nmol/l, p 550 nmol/l, n = 18). Five patients developed elevated HbA 1c levels (> 6.5%). In men 177 Lu-octreotate therapy induced transient inhibitory effects on spermatogenesis, but non-SHBG-bound T levels remained unaffected. In the long term, gonadotropin levels decreased significantly in postmenopausal women. Only a few patients developed hypothyroidism or elevated levels of HbA 1c . Therefore, PRRT with 177 Lu-octreotate can be regarded as a safe treatment modality with respect to short- and long-term endocrine function. (orig.)

  8. Potential renal toxicity bio-markers indicating radiation injury after 177Lu-octreotate treatment

    International Nuclear Information System (INIS)

    Dalmo, J.; Forssell-Aronsson, E.; Westberg, E.; Toernqvist, M.; Svedborn, L.; Barregaerd, L.

    2015-01-01

    Full text of publication follows. The kidneys are one of the most exposed non-tumor tissues and regarded as one of the main dose-limiting organs in peptide receptor radionuclide therapy (PRRT). [ 177 Lu-DOTA0, Tyr3]-octreotate ( 177 Lu-octreotate) has shown promising results in the treatment of somatostatin receptor over-expressing neuroendocrine tumors, but optimization is still needed. The ability to give each patient as much 177 Lu-octreotate as possible without inducing nephrotoxicity is necessary for an efficient treatment. However, due to large inter-individual differences in uptake and retention in the kidneys, there is a need for efficient methods that can indicate renal injury early. A possible way is to identify bio-markers for high risk of radiation nephrotoxicity. The aim of this study was to investigate the potential of using urinary retinol binding protein (RBP), and blood valinhydantoin (VH) as bio-markers of nephrotoxicity on adult mice after 177 Lu-octreotate treatment. BALB/c nude mice (n=6/group) were i.v. injected with 60 MBq or 120 MBq of 177 Lu-octreotate. The control group was mock treated with saline. Spot urine samples were collected before injection, and 14, 30, 60 and 90 days after injection. Analysis of RBP4 and creatinine was performed using Mouse RBP4 ELISA kit and Creatinine kit from R/D Systems, respectively. Erythrocytes were separated from whole blood samples collected 90 days after injection, and analysed for VH by LC-MS/MS. The ratio between VH and a volumetric standard was calculated. The RBP/creatinine level increased with time in both groups given 177 Lu-octreotate, with earlier and higher response for the 120 MBq group. No clear change in VH level between the different groups was observed. The results show that RBP may be a promising new bio-marker for radiation induced kidney toxicity. The presently used method based on VH was not sensitive enough to be used as kidney toxicity marker. Further studies on mice are ongoing to

  9. Tumor localization of 131I-labeled antibodies by radionuclide imaging

    International Nuclear Information System (INIS)

    Ghose, T.; Tai, J.; Aquino, J.; Guclu, A.; Norvell, S.; MacDondald, A.

    1975-01-01

    Intravenous injections of 131 I-labeled anti-EL4 lymphoma antibodies showed progressive localization of radioactivity in EL4 transplants but not in B16 melanoma in mice carrying both tumors. Normal rabbit globulin labeled with 131 I did not localize in either tumor and cleared more slowly from the internal organs. Metastatic localization of intravenous 131 I-labeled anti-tumor antibodies was also observed in two cancer patients. (U.S.)

  10. 68Ga/177Lu-labeled DOTA-TATE shows similar imaging and biodistribution in neuroendocrine tumor model.

    Science.gov (United States)

    Liu, Fei; Zhu, Hua; Yu, Jiangyuan; Han, Xuedi; Xie, Qinghua; Liu, Teli; Xia, Chuanqin; Li, Nan; Yang, Zhi

    2017-06-01

    Somatostatin receptors are overexpressed in neuroendocrine tumors, whose endogenous ligands are somatostatin. DOTA-TATE is an analogue of somatostatin, which shows high binding affinity to somatostatin receptors. We aim to evaluate the 68 Ga/ 177 Lu-labeling DOTA-TATE kit in neuroendocrine tumor model for molecular imaging and to try human-positron emission tomography/computed tomography imaging of 68 Ga-DOTA-TATE in neuroendocrine tumor patients. DOTA-TATE kits were formulated and radiolabeled with 68 Ga/ 177 Lu for 68 Ga/ 177 Lu-DOTA-TATE (M-DOTA-TATE). In vitro and in vivo stability of 177 Lu-DOTA-TATE were performed. Nude mice bearing human tumors were injected with 68 Ga-DOTA-TATE or 177 Lu-DOTA-TATE for micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging separately, and clinical positron emission tomography/computed tomography images of 68 Ga-DOTA-TATE were obtained at 1 h post-intravenous injection from patients with neuroendocrine tumors. Micro-positron emission tomography and micro-single-photon emission computed tomography/computed tomography imaging of 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE both showed clear tumor uptake which could be blocked by excess DOTA-TATE. In addition, 68 Ga-DOTA-TATE-positron emission tomography/computed tomography imaging in neuroendocrine tumor patients could show primary and metastatic lesions. 68 Ga-DOTA-TATE and 177 Lu-DOTA-TATE could accumulate in tumors in animal models, paving the way for better clinical peptide receptor radionuclide therapy for neuroendocrine tumor patients in Asian population.

  11. Study of the production of 177Lu through 176Yb (n, γ) 177Yb → 177Lu nuclear reaction

    International Nuclear Information System (INIS)

    Silva, Giovana Pasqualini da; Osso Junior, Joao Alberto

    2007-01-01

    The beta minus emitter 177 Lu is a promising therapeutic radioisotope for the curative treatment of cancer using labelled proteins. It has a half - life of T 1/2 = 6.71 day and maximum and average β - energies of 421 and 133 keV, resulting in a short range of radiation in tissue. The decay is accompanied by the emission of low energy γ-radiation with 208.3 keV (11%) and 113 keV (6.4%) suitable for simultaneous imaging, 177 Lu can be produced by two different routes, namely, by irradiation of natural Lu 2 O 3 target ( 176 Lu, 2.6%) or enriched (in 176 Lu) Lu 2 O 3 target, as also by irradiation of Yb target (Yb 2 O 3 ) followed by radiochemical separation of 177 Lu from Yb isotopes. The objective of this work is to study the production of 177 Lu through the indirect 176 Yb(n,γ) 177 Yb → 177 Lu nuclear reaction. The results of the production yield of 177 Lu will be shown and compared with the direct reaction. The method of choice for the chemical separation between Lu and Yb was the ion exchange, using an cation exchange resin in Cl - form and α-HIBA as eluent. Preliminary results showed a good separation of 177 Lu from Yb 2 O 3 indirect targets. (author)

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

    International Nuclear Information System (INIS)

    Liang Jixin; Li Hongyu; Xiang Xueqin; Luo Zhifu; Luo Hongyi; Hu Liansheng; Chen Yang; Zhuang Ling; Deng Xinrong

    2012-01-01

    The aim of this project is to evaluate the biodistribution of 177 Lu-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, 177 Lu-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. 177 Lu-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 177 Lu-DOTA-SP in the kidneys, indicating the excretion mainly by renal pathway. In addition, 177 Lu-DOTA-SP was washed out from the blood quickly. Bio- distribution of 177 Lu-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)

  13. Time-dependent transcriptional response of GOT1 human small intestine neuroendocrine tumor after 177Lu[Lu]-octreotate therapy.

    Science.gov (United States)

    Spetz, Johan; Rudqvist, Nils; Langen, Britta; Parris, Toshima Z; Dalmo, Johanna; Schüler, Emil; Wängberg, Bo; Nilsson, Ola; Helou, Khalil; Forssell-Aronsson, Eva

    2018-05-01

    Patients with neuroendocrine tumors expressing somatostatin receptors are often treated with 177 Lu[Lu]-octreotate. Despite being highly effective in animal models, 177 Lu[Lu]-octreotate-based therapies in the clinical setting can be optimized further. The aims of the study were to identify and elucidate possible optimization venues for 177 Lu[Lu]-octreotate tumor therapy by characterizing transcriptional responses in the GOT1 small intestine neuroendocrine tumor model in nude mice. GOT1-bearing female BALB/c nude mice were intravenously injected with 15 MBq 177 Lu[Lu]-octreotate (non-curative amount) or mock-treated with saline solution. Animals were killed 1, 3, 7 or 41 d after injection. Total RNA was extracted from the tumor samples and profiled using Illumina microarray expression analysis. Differentially expressed genes were identified (treated vs. control) and pathway analysis was performed. Distribution of differentially expressed transcripts indicated a time-dependent treatment response in GOT1 tumors after 177 Lu[Lu]-octreotate administration. Regulation of CDKN1A, BCAT1 and PAM at 1 d after injection was compatible with growth arrest as the initial response to treatment. Upregulation of APOE and BAX at 3 d, and ADORA2A, BNIP3, BNIP3L and HSPB1 at 41 d after injection suggests first activation and then inhibition of the intrinsic apoptotic pathway during tumor regression and regrowth, respectively. Transcriptional analysis showed radiation-induced apoptosis as an early response after 177 Lu[Lu]-octreotate administration, followed by pro-survival transcriptional changes in the tumor during the regrowth phase. Time-dependent changes in cell cycle and apoptosis-related processes suggest different time points after radionuclide therapy when tumor cells may be more susceptible to additional treatment, highlighting the importance of timing when administering multiple therapeutic agents. Copyright © 2018 The Authors. Published by Elsevier Inc. All

  14. Long-term toxicity of [177Lu-DOTA0,Tyr3]octreotate in rats

    International Nuclear Information System (INIS)

    Rolleman, Edgar J.; Krenning, Eric P.; Bernard, Bert F.; Visser, Monique de; Bijster, Magda; Jong, Marion de; Visser, Theo J.; Vermeij, Marcel; Lindemans, Jan

    2007-01-01

    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 [ 177 Lu-DOTA 0 ,Tyr 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 [ 177 Lu-DOTA 0 ,Tyr 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 [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate with intervals of a day, a week or a month significantly influenced serum creatinine (469±18, 134±70 and 65±15 μmol/l, respectively; p 177 Lu-DOTA 0 ,Tyr 3 ]octreotate resulted in severe renal damage in rats as indicated by proteinuria, elevated serum creatinine and histological damage. This damage was dose dependent and became overt between 100 and 200 days after treatment. Dose fractionation had significant beneficial effects on kidney function. Also, lysine co-injection successfully prevented functional damage. (orig.)

  15. Development of a lyophilized formulation for preparing the radiopharmaceutical 177Lu-DOTA-Anti-CD20

    International Nuclear Information System (INIS)

    Serrano E, L. A.

    2015-01-01

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

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

    International Nuclear Information System (INIS)

    Mathe, Domokos; Balogh, Lajos; Polyak, Andras; Kiraly, Reka; Marian, Terez; Pawlak, Dariusz; Zaknun, John J.; Pillai, Maroor R.A.; Janoki, Gyozo A.

    2010-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-02-15

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

  18. Evidence for inelastic neutron acceleration by the 177Lu isomer

    International Nuclear Information System (INIS)

    Roig, O.; Belier, G.; Meot, V.; Daugas, J.-M.; Abt, D.; Aupiais, J.; Jutier, Ch.; Petit, G. Le; Letourneau, A.; Marie, F.; Veyssiere, Ch.

    2006-01-01

    The neutron burnup cross section σ burnup m on the long-lived metastable state of 177 Lu has been measured from a specially designed isomeric target. The Maxwellian averaged cross section obtained for this reaction on 177 Lu m (J π =23/2 - ) is σ burnup m =626±45 b at the reactor temperature T=323 K. The difference between the burnup cross section and the previously measured capture cross section σ n,γ clearly shows a possible existence of 177 Lu m deexcitation via (n,n ' ) inelastic neutron acceleration channels. The results are interpreted in terms of a statistical approach using parameters from a deformed optical potential calculation

  19. 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.)

  20. Quality audit programme for {sup 99m}Tc and {sup 131}I radioactivity measurements with radionuclide calibrators

    Energy Technology Data Exchange (ETDEWEB)

    Joseph, Leena [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)], E-mail: leena@barc.gov.in; Anuradha, R.; Kulkarni, D.B. [Radiation Safety Systems Division, Bhabha Atomic Research Centre, Mumbai 400 085 (India)

    2008-06-15

    The use of radiopharmaceuticals in nuclear medicine for diagnosis and therapy has increased over the years with {sup 99m}Tc and {sup 131}I being most widely used. Quality audit programmes for radioactivity measurements of {sup 131}I have been ongoing and the 12th audit was recently conducted among seventy nuclear medicine centres (NMC) in India. An audit for the activity measurements of {sup 99m}Tc was conducted for the first time among ten NMCs in Mumbai, India. These programmes for radioactivity measurements have become very important to establish traceability of measurements to national and international standards and ensure accurate calibration of radionuclide calibrators. The results of both the audits are very encouraging. Ninety-four percent of the NMCs for {sup 131}I activity measurements were within a window of {+-}10% and for {sup 99m}Tc one NMC was deviating more than {+-}10%. The methodology adopted for the audit and results are discussed in detail in this paper.

  1. 131I-orthoiodohippurate renogram exploring the relationship among the radionuclide renography, hydronephrosis and renal function

    International Nuclear Information System (INIS)

    Zha Jinshun; Su Yingrui; Jiang Yan

    2009-01-01

    Objective: To investigate the 131 I-orthoiodohippurate renography with hydronephrosis and renal function, in order to further clarify the clinical diagnosis and treatment of hydronephrosis and provide a reliable basis. Methods: Retrospective analysis the results of 131 I-orthoiodohippurate renography in 120 patients whose urology inpatients. In accordance with the side of hydronephrosis, bilateral hydronephrosis and light, moderate and severe packet. The features of renography and the changes of functional parameter values in each group was analysised. And compared with the results of clinical evaluation about renal function and blood urea nitrogen (BUN), creatinine (Cr) levels. SPSS.16 statistical software was used for statistical analysis. Results: The incidence of abnormal renal function in varying degrees of hydronephrosis were significantly higher than those without hydronephrosis (98.9% vs. 39.3%, χ 2 =87.492, P 2 =13.848, P 131 I-orthoiodohippurate renography there is a higher sensitivity on the assessment of hydronephrosis and renal function, but lack of specificity. The analysis should be combination with clinical situation. (authors)

  2. Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

    International Nuclear Information System (INIS)

    Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

    2015-01-01

    177 Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177 Lu-EDTMP for MBP palliation. 177 Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177 Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177 Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

  3. Metastatic Bone Pain Palliation using (177)Lu-Ethylenediaminetetramethylene Phosphonic Acid.

    Science.gov (United States)

    Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R; Bahrami-Samani, Ali

    2015-01-01

    (177)Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using (177)Lu-EDTMP for MBP palliation. (177)Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. (177)Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. (177)Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for

  4. Metastatic Bone Pain Palliation using 177Lu-Ethylenediaminetetramethylene Phosphonic Acid

    Science.gov (United States)

    Alavi, Mehrosadat; Omidvari, Shapour; Mehdizadeh, Alireza; Jalilian, Amir R.; Bahrami-Samani, Ali

    2015-01-01

    177Lu-ethylenediaminetetramethylene phosphonic acid (EDTMP) is presently suggested as an excellent bone seeking radionuclide for developing metastatic bone pain (MBP) palliation agent owing to its suitable nuclear decay characteristics. To find the exact dosage and its efficiency, this clinical study was performed on the human being, using 177Lu-EDTMP for MBP palliation. 177Lu-EDTMP was prepared by Iran, atomic energy organization. Thirty consecutive patients with determined tumors, incontrollable MBP, and positive bone scan at 4 weeks before the beginning of the study participated in this study in the nuclear medicine ward. 177Lu-EDTMP in the form of sterile slow IV injection was administered with a dose of 29.6 MBq/kg. Short form of brief pain inventory questionnaire was used to evaluate the efficiency of the intervention. Questionnaires were filled out by an expert nuclear physician every 2 weeks while the cell blood count was also checked every 2 weeks up to 12 weeks for evaluation of bone marrow suppression and hematological toxicity. Furthermore, whole body scan was done at days 1, 3, and 7. Twenty-five patients showed a significant pain relief since 2 weeks after the injection, and continued until the end of the follow up period (12 weeks). There were no significant early complications such as bone marrow suppression, hematological toxicity, and no systemic adverse effects. No complication was observed in renal function. Twenty one patients showed flare phenomenon that was started after the 12.2 ± 1.78 h lasting for 38.4 ± 23.08. Sixteen patients (53%) were completely treated; nine patients (30%) showed a partial response, and five patients (17%) had no response to treatment. Total response to treatment was achieved in 25 patients (83%). At the end of the evaluation, no bone marrow suppression or hematologic toxicity was observed. 177Lu-EDTMP has shown suitable physical and biological properties with good results in long term bone pain relief for patients

  5. Use of 177Lu-dotatate in the treatment of iodine refractory thyroid carcinomas.

    Science.gov (United States)

    Oliván-Sasot, P; Falgás-Lacueva, M; García-Sánchez, J; Vera-Pinto, V; Olivas-Arroyo, C; Bello-Arques, P

    In a patient with a differentiated thyroid cancer the standard treatment protocol to be followed is surgery, ablation of thyroid remnants with 131 Iodine ( 131 I), and TSH suppression. However, the treatment with 131 I is not effective in some cases, and it no longer becomes a therapeutic option due to cell de-differentiation with loss of 131 I uptake. Systemic treatment can be used as other options, although patients are not always responsive; thus, the disease may progress and therapeutic options may run out. Endocrine tumours may express somatostatin receptors,and this characteristic has been used, not only for diagnosis, but also for their treatment through somatostatin analogue labelling with radioactive isotopes. This was the case of a patient suffering from iodine-refractory follicular thyroid carcinoma, with somatostatin receptors expression, treated with 177 Lu-DOTATATE, showing an excellent clinical and analytical response. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  6. Combined effect of 131I and osteotropic radionuclide of 90Sr and 45Ca

    International Nuclear Information System (INIS)

    Borisova, V.V.; Vetukh, V.A.; Rusanova, O.V.

    1988-01-01

    Combined effect of 131 I and osteotropic 45 Ca and 90 Sr on blood formation, reproduction and life span of laboratory animals was considered. It was shown that combined irradiation of thyroid and bone marrow with doses not exceeding or equal 1 Gy doesn't result in changes of blood formation or life span, but leads to definite violations in stem spermatogonia which bring about intra-uterine death of progeny. This fact is explained as a result of indirect radiation effect for the dose for gonads was 0.1 Gy. 3 tabs

  7. Preparation of 177Lu-DTPA-BIS-BIOTIN and biodistribution evaluation in normal mice

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Du Jin

    2010-01-01

    The labeling method for 177 Lu-DTPA-BIS-BIOTIN was established, and the biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice was carried out as well. Under the optimal experimental condition (DTPA-BIS-BIOTIN 25 μg, pH=4.5 reacting at 80 degree C for 20 min), the labeling yield of 177 Lu-DTPA-BIS-BIOTIN is more than 99.0%. 177 Lu-DTPA-BIS-BIOTIN shows pretty good in vitro stability. The biodistribution of 177 Lu-DTPA-BIS-BIOTIN in normal mice shows a rapid blood clearance. The uptake of 177 Lu-DTPA-BIS-BIOTIN is mainly accumulated in liver, spleen and kidney. 177 Lu-DTPA-BIS-BIOTIN is excreted by kidney. The results provide the basis for further study on 177 Lu-DTPA-BIS-BIOTIN used in pretargeted radioimage and radiotherapy of cancer. (authors)

  8. 177Lu-DOTA-Bevacizumab: Radioimmunotherapy Agent for Melanoma.

    Science.gov (United States)

    Camacho, Ximena; Calzada, Victoria; Fernandez, Marcelo; Alonso, Omar; Chammas, Roger; Riva, Eloisa; Gambini, Juan Pablo; Cabral, Pablo

    2017-01-01

    Vascular endothelial growth factor (VEGF) is one of the classic factors to tumor-induced angiogenesis in several types, including melanoma. Bevacizumab is a humanized monoclonal antibody directed against VEGF. To radiolabel Bevacizumab with 177-Lutetium as a potential radioimmunotherapy agent for melanoma. Bevacizumab was derivatized with DOTA-NHS-ester at 4 ºC for 18 h. DOTABevacizumab was radiolabeled with 177LuCl3 (15 MBq/mg) at 37 ºC for 1 h. The studies were performed in healthy and B16F1 tumor-bearing C57BL/6J mice at 24 and 48 h (n = 5). Scinthigraphic imaging studies were performed at 24 h to determine the radiochemical stability, targeting specificity and pharmacokinetics of the 177Lutetium-labeled antibody. DOTA-Bevacizumab was efficiently labeled with 177LuCl3 at 37 °C. The in-vitro stability of labeled product was optimal over 72 h. In-vivo biodistribution studies showed a high liver and tumor uptake of 177Lu-DOTA-Bevacizumab, with tumor-to-muscle ratios of 11.58 and 6.37 at 24 and 48 h p.i. Scintigraphic imaging of melanoma tumor-bearing C57BL/6J mice showed liver and a high tumor selective uptake of 177Lu-DOTA-Bevacizumab at 24 h. Our results support the potential role of 177Lu-DOTA-Bevacizumab as a novel radioimmunotherapy agent for melanoma. We hope that these novel molecular imaging agents will open the path to new diagnostic and therapeutic strategies for Melanoma disease. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-15

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

  10. {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.)

  11. Tumor-targeting properties of 90Y- and 177Lu-labeled α-melanocyte stimulating hormone peptide analogues in a murine melanoma model

    International Nuclear Information System (INIS)

    Miao Yubin; Hoffman, Timothy J.; Quinn, Thomas P.

    2005-01-01

    The purpose of this study was to compare the tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH in a murine melanoma mouse model. Methods: The in vitro properties of cellular internalization and retention of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were studied in B16/F1 murine melanoma cells. The pharmacokinetics of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were determined in B16/F1 melanoma-bearing C57 mice. Results: 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH exhibited fast cellular internalization and extended cellular retention in B16/F1 cells. High receptor-mediated tumor uptake and retention coupled with fast whole-body clearance of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were demonstrated in B16/F1 tumor-bearing C57 mice. The tumor uptakes of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH were 25.70±4.64 and 14.48±0.85 %ID/g at 2 h, and 14.09±2.73 and 17.68±3.32 %ID/g at 4 h postinjection. There was little activity accumulated in normal organs except for kidney. Conclusions: High tumor-targeting properties of 90 Y-DOTA-Re(Arg 11 )CCMSH and 177 Lu-DOTA-Re(Arg 11 )CCMSH highlighted their potential as radiopharmaceuticals for targeted radionuclide therapy of melanoma in further investigations

  12. Production and Stability Study of High Activity 177Lu-Substance P as a Radiopharmaceutical for Malignant Tumors Treatment

    International Nuclear Information System (INIS)

    Araujo, E.B. de; Lima, C.M. de; Pujatti, P.B.; Mengatti, J.

    2009-01-01

    In recent years, a high number of new developments in target therapies have emerged and the presence of peptide receptors and transporters at the cell membrane of several tumors constitutes the basis of the clinical use of specific radiolabeled ligands, such as Substance P (SP). SP is an 11-amino acid neuropeptide member of the family of tachykinins, characterized by the C-terminal sequence Phe-X- Gly-Leu-Met-NH 2 . It has been well established that SP plays an important role in modulating pain transmission from peripheral and central primary afferents and this peptide may be also involved in the pathogenesis of inflammatory diseases. SP receptors are also found in brain, lymphoid tissues, vessels, gut smooth muscle, airway glands and bronchiolar walls. In receptor autoradiography of tumor specimens ex vivo, SP receptors were found on glioblastoma, medullary thyroid cancer, non- small cell lung cancer and carcinoma of pancreas, but the incidence is low in the last two. The introduction of radiolabeled SP for peptide receptor radiotherapy can be an alternative to treat these tumors by radionuclide therapy or loco-regional instillation. Several radioisotopes have been applied to radiolabel peptides for radionuclide therapy and 6.7 day half-life 177 Lu has emerged as a promising β- emitter for this purpose. The energy (497 keV) and mean range (670 μm) of lutetium-177 β particles are ideal for small tumors and micro-metastatic disease treatment. Because it also emits γ rays (208 keV, 11% abundance), imaging of 177 Lu-labeled endoradiotherapeutic agents is also possible. The goal of the present work was to determine the best radiolabeling conditions and the stability of SP complexed to DOTA chelator, using 177 Lu as radionuclide. The optimized condition was applied to produce a high activity and stable 177Lu-DOTA-SP, as a radiopharmaceutical for malignant tumors treatment. Substance P was radiolabeled at different conditions in order to determine the best

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

    DEFF Research Database (Denmark)

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

    2014-01-01

    for small, established tumors. A combination of such radionuclides may be successful in regimens of radioimmunotherapy. In this study, rats were treated by sequential administration of first a 177Lu-labeled antibody, followed by a 211At-labeled antibody 25 days later. METHODS: Rats bearing solid colon...... carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96....... The rats suffered from reversible myelotoxicity after treatment. CONCLUSIONS: Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect....

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

    International Nuclear Information System (INIS)

    Luna G, M. A.

    2014-01-01

    . Biokinetic studies were accomplished in athymic mice with U87MG induced tumors. The radiochemical purity for all 177 Lu-RGD derivatives was 96 ± 2%. 177 Lu-absorbed doses per injected activity delivered to U87MG tumors were 0.357±0.052 Gy/MBq (multimer), 0.252±0.027 Gy/MBq (dimer) and 0.112±0.018 Gy/MBq (monomer). 177 Lu-labeled dimeric and multimeric RGD peptides demonstrated properties suitable for targeted radionuclide therapy and multimeric system for plasmonic photothermal therapy of tumors expressing α(v)β(3) and α(v)β(5) integrin s. (Author)

  15. Internal radiotherapy and dosimetric study for {sup 111}In/{sup 177}Lu-pegylated liposomes conjugates in tumor-bearing mice

    Energy Technology Data Exchange (ETDEWEB)

    Wang, H.-E. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Yu, H.-M. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lu, Y.-C. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Heish, N.-N. [National Health Research Institute, Taipei, Taiwan (China); Tseng, Yun-Long [Taiwan Liposome Co. Ltd., Taipei, Taiwan (China); Huang, K.-L. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chuang, K.-T. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Chen, Chin-Hsiung [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Hwang, J.-J. [Institute of Radiological Sciences, National Yang Ming University, Taipei, Taiwan (China); Lin, W.-J. [Institute of Nuclear Energy Research, Taoyuan, Taiwan (China); Wang, Shyh-Jen [Department of Nuclear Medicine, Taipei Veterans General Hospital, Taipei, Taiwan (China); Ting, G. [National Health Research Institute, Taipei, Taiwan (China); Whang-Peng, Jacqueline [National Health Research Institute, Taipei, Taiwan (China); Deng, W.-P. [Graduate Institute of Biomedical Materials, Taipei Medical University, Taipei, Taiwan (China)]. E-mail: wpdeng@tmu.edu.tw

    2006-12-20

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. Methods: The DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with {sup 111}In/{sup 177}Lu-(oxine){sub 3} to afford {sup 111}In/{sup 177}Lu-liposome. The stability of {sup 111}In/{sup 177}Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of {sup 111}In/{sup 177}Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. Results: The incorporation efficiency of {sup 111}In/{sup 177}Lu into liposomes was 95%. After incubation at 37 {sup o}C for 72 h in serum, more than 83% of radioactivity was still retained in the intact {sup 111}In/{sup 177}Lu-liposomes. The biodistribution of {sup 111}In-liposomes showed that the radioactivity in the blood decreased from 23.14{+-}8.16%ID/g at 1 h to 0.02{+-}0.00%ID/g at 72 h post-injection (p.i.), while reaching its maximum accumulation in tumors at 48 h p.i., with half-life in blood of 10.2 h. The results were supported by that of {sup 177}Lu-liposomes. Scintigraphic imaging with {sup 111}In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from {sup 177}Lu-liposomes was 5.74x10{sup -5} Gy/MBq. Conclusions: This study provides an in vivo characterization and dosimetric evaluation for the use of liposome systems as carriers in targeted radionuclide therapy. The results suggest that adequate tumor targeting as well as dose delivered to tumors could be achieved by the use of radionuclide targeted liposomes.

  16. Study On Preparation Of 177Lu-EDTMP For Metastatic Bone Pain Palliation Treatment

    International Nuclear Information System (INIS)

    Nguyen Thanh Binh; Dang Ho Hong Quang; Duong Van Dong; Chu Van Khoa; Nguyen Thi Hien

    2011-01-01

    Ethylene diamine tetramethylene phosphonate (EDTMP) is one of the most widely used ligands which forms stable complexes with various radionuclides and all the complexes showed high bone uptake in biodistribution studies. EDTMP has a high affinity to skeleton and osteoblastic bone metastases and many EDTMP chelates posses a considerably high stability.This stimulated application of the ligand as the in-vivo carrier of various radionuclides, intended for both therapy and diagnosis of osteoblastic lesions.The present study intends to formulate EDTMP kits, label them with 177 Lu, quality control and in-vitro stability studies. This paper presents some research results on the optimal conditions for labeling EDTMP kit with Lu-177 of low specific activity that was produced on the IVV-9 reactor at the Nuclear Research Institute. (author)

  17. Quality of life assessment in radionuclide therapy: a feasibility study of the EORTC QLQ-C30 questionnaire in palliative 131I-lipiodol therapy

    International Nuclear Information System (INIS)

    Brans, B.; Lambert, B.; De Beule, E.; De Winter, F.; Dierckx, R.A.; Van Belle, S.; Van Vlierberghe, H.; De Hemptinne, B.

    2002-01-01

    The good tolerance of radionuclide therapy has frequently been proposed as a major advantage. This study explored the feasibility of using the EORTC QLQ-C30 questionnaire in palliative iodine-131 lipiodol therapy for hepatocellular carcinoma. Questionnaires were completed during interviews in which all symptoms, co-morbidity and medication were assessed at baseline within 1 week before 131 I-lipiodol therapy, and subsequently after 1 and 3 months, in 20 patients treated with locoregional, intra-arterial 131 I-lipiodol therapy with or without cisplatin. Principal observations were that (1) a number of important scales, i.e. overall quality of life, physical functioning and pain, worsened between 0 and 3 months after 131 I-lipiodol therapy, irrespective of tumour response, and (2) the occurrence of clinical side-effects was associated with a negative impact on quality of life and physical functioning 1 and 3 months after 131 I-lipiodol. The QLQ-C30 can be regarded as a feasible method for quality of life assessment in 131 I-lipiodol therapy for hepatocellular carcinoma and possibly in other radionuclide therapies. These observations should be related to the impact of other treatment modalities on quality of life. (orig.)

  18. Tumour control probability derived from dose distribution in homogeneous and heterogeneous models: assuming similar pharmacokinetics, 125Sn–177Lu is superior to 90Y–177Lu in peptide receptor radiotherapy

    International Nuclear Information System (INIS)

    Walrand, Stephan; Hanin, François-Xavier; Pauwels, Stanislas; Jamar, François

    2012-01-01

    Clinical trials on 177 Lu– 90 Y therapy used empirical activity ratios. Radionuclides (RN) with larger beta maximal range could favourably replace 90 Y. Our aim is to provide RN dose-deposition kernels and to compare the tumour control probability (TCP) of RN combinations. Dose kernels were derived by integration of the mono-energetic beta-ray dose distributions (computed using Monte Carlo) weighted by their respective beta spectrum. Nine homogeneous spherical tumours (1–25 mm in diameter) and four spherical tumours including a lattice of cold, but alive, spheres (1, 3, 5, 7 mm in diameter) were modelled. The TCP for 93 Y, 90 Y and 125 Sn in combination with 177 Lu in variable proportions (that kept constant the renal cortex biological effective dose) were derived by 3D dose kernel convolution. For a mean tumour-absorbed dose of 180 Gy, 2 mm homogeneous tumours and tumours including 3 mm diameter cold alive spheres were both well controlled (TCP > 0.9) using a 75–25% combination of 177 Lu and 90 Y activity. However, 125 Sn– 177 Lu achieved a significantly better result by controlling 1 mm-homogeneous tumour simultaneously with tumours including 5 mm diameter cold alive spheres. Clinical trials using RN combinations should use RN proportions tuned to the patient dosimetry. 125 Sn production and its coupling to somatostatin analogue appear feasible. Assuming similar pharmacokinetics 125 Sn is the best RN for combination with 177 Lu in peptide receptor radiotherapy justifying pharmacokinetics studies in rodent of 125 Sn-labelled somatostatin analogues. (paper)

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

    Energy Technology Data Exchange (ETDEWEB)

    Ortega S, D.

    2015-07-01

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

  20. 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.

  1. Long-Term Efficacy, Survival, and Safety of [177Lu-DOTA0,Tyr3]octreotate in Patients with Gastroenteropancreatic and Bronchial Neuroendocrine Tumors.

    Science.gov (United States)

    Brabander, Tessa; van der Zwan, Wouter A; Teunissen, Jaap J M; Kam, Boen L R; Feelders, Richard A; de Herder, Wouter W; van Eijck, Casper H J; Franssen, Gaston J H; Krenning, Eric P; Kwekkeboom, Dik J

    2017-08-15

    Purpose: Bronchial and gastroenteropancreatic neuroendocrine tumors (NET) are slow-growing tumors, which frequently express somatostatin receptors on their cell membranes. These receptors are targets for therapy with Lutetium-177-labeled somatostatin analogues. We have treated over 1,200 patients with peptide receptor radionuclide therapy (PRRT) with [ 177 Lu-DOTA 0 ,Tyr 3 ]octreotate ( 177 Lu-DOTATATE) since the year 2000 and present the results on efficacy, survival, and toxicity of this therapy. Experimental Design: For safety analysis, 610 patients treated with a cumulative dose of at least 100 mCi (3.7 GBq) 177 Lu-DOTATATE were included. A subgroup of 443 Dutch patients who were treated with a cumulative dose of at least 600 mCi (22.2 GBq) 177 Lu-DOTATATE before 2013 was further analyzed for efficacy and survival. Results: The objective response rate of the total group of patients was 39%. Stable disease was reached in 43% of patients. Progression-free survival (PFS) and overall survival (OS) for all NET patients were 29 months [95% confidence interval (CI), 26-33 months] and 63 months (95% CI, 55-72 months). Long-term toxicity included acute leukemia in four patients (0.7%) and myelodysplastic syndrome in nine patients (1.5%). No therapy-related long-term renal or hepatic failure occurred. Conclusions: PRRT with 177 Lu-DOTATATE is a favorable therapeutic option in patients with metastatic bronchial and gastroenteropancreatic NETs that express somatostatin receptors. PRRT with 177 Lu-DOTATATE is safe with few side-effects and shows good response rates with PFS of 29 months and OS of 63 months. Clin Cancer Res; 23(16); 4617-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  2. 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.)

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

    Science.gov (United States)

    Seregni, E; Maccauro, M; Chiesa, C; Mariani, L; Pascali, C; Mazzaferro, V; De Braud, F; Buzzoni, R; Milione, M; Lorenzoni, A; Bogni, A; Coliva, A; Lo Vullo, S; Bombardieri, E

    2014-02-01

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

  4. 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.)

  5. Improvement in the 111In-DTPA-TYR3-octreotide and 177Lu-DOTATYR3- octreotate production

    International Nuclear Information System (INIS)

    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

    2009-01-01

    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 [ 177 Lu-DOTA-Tyr 3 ]octreotate (DOTATATE) for therapy. The aim of this work is to establish and validate the labeling, the quality control procedures of DTPA-Tyr 3 -Octreotide (DTPA-Oct) and DOTA-Tyr 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 111 InCl 3 (Nordion) and in hot-cell with 177 LuCl 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 -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 111 In-DTPA-Oct and 177 Lu-DOTATATE was confirmed in the first comparative clinical groups. The methods were validated and 46.287 GMBq of 111 In-DTPA-Oct and 1,193 GBq of 177 Lu-DOTATATE were distributed in 2008, to nuclear medicine services in Brazil. (author)

  6. [Treatment of Gastroenteropancreatic Neuroendocrine Tumors with 177Lu-DOTA-TATE: Experience of the Portuguese Institute of Oncology in Porto].

    Science.gov (United States)

    Sampaio, Inês Lucena; Luiz, Henrique Vara; Violante, Liliana Sobral; Santos, Ana Paula; Antunes, Luís; Torres, Isabel; Sanches, Cristina; Azevedo, Isabel; Duarte, Hugo

    2016-11-01

    The purpose of this article is to report the experience of the Portuguese Institute of Oncology - Porto in the treatment of gastroenteropancreatic neuroendocrine tumors with 177Lu-DOTA-TATE, regarding the safety and efficacy of this treatment modality. A retrospective analysis of clinical reports of patients with gastroenteropancreatic neuroendocrine tumors undergoing treatment with 177Lu-DOTA-TATE between April 2011 and November 2013 was performed. Thirty six cases were reviewed and 30 completed all 3 cycles of 177Lu-DOTA-TATE (83.3%). In these patients it was registered: acute side effects in 8.9% of cycles; grade 3 CTCAE liver toxicity in 13.3% of patients (all with previous abnormal liver function); absence of significant renal or hematologic toxicity; symptomatic improvement in 71.4% of patients; median overall time to progression of 25.6 months; median overall survival from diagnosis of 121.7 months. Patients with higher expression of somatostatin receptors had longer progression-free survival and overall survival times (p DOTA-TATE is an effective, safe and well-tolerated treatment, as evidenced in our study by the following findings: symptomatic improvement in most patients and increased time to disease progression and survival (especially in those with higher sstr expression), with acute and significant subacute/chronic side effects reported only in a minority of cases. Peptide receptor radionuclide therapy with 177Lu-DOTA-TATE is a promising treatment for patients with gastroenteropancreatic neuroendocrine tumors, with demonstrated benefits in terms of safety and efficacy.

  7. Formulation of an inhibitor radiopharmaceutical of prostatic antigen of 177Lu-Glu-Nh-CO-Nh-Lys membrane

    International Nuclear Information System (INIS)

    Ortega S, D.

    2015-01-01

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

  8. Bulk Scale Formulation of Therapeutic Doses of Clinical Grade Ready-to-Use 177Lu-DOTA-TATE: The Intricate Radiochemistry Aspects.

    Science.gov (United States)

    Mathur, Anupam; Prashant, Vrinda; Sakhare, Navin; Chakraborty, Sudipta; Vimalnath, K V; Mohan, Repaka Krishna; Arjun, Chanda; Karkhanis, Barkha; Seshan, Ravi; Basu, Sandip; Korde, Aruna; Banerjee, Sharmila; Dash, Ashutosh; Sachdev, Satbir Singh

    2017-09-01

    177 Lu-DOTA-TATE is a clinically useful and promising therapeutic radiopharmaceutical for peptide receptor radionuclide therapy of neuroendocrine tumors (NETs) overexpressing somatostatin receptors. Currently, the radiopharmaceutical is prepared in-house at nuclear medicine centers, thereby restricting its use to limited centers only. In this article, the authors describe systematic studies toward bulk scale formulation of "ready-to-use" 177 Lu-DOTA-TATE using medium specific activity 177 Lu (740-1110 GBq/mg) at a centralized radiopharmacy facility. In an optimized protocol, 177 Lu-DOTA-TATE synthesis was carried out by direct heating of 177 LuCl 3 (Sp. act. 740-1110 GBq/mg) with DOTA-TATE peptide (1.5-3.0 equivalents) in ammonium acetate buffer (0.2 M) containing 2,5-dihydroxy benzoic acid (gentisic acid). Thereafter, the crude labeled product was purified using a Sep-Pak ® C18 column and diluted with acetate buffer-gentisic acid (1.5% w/v) solution to final radioactive concentration of 740 MBq/mL. This was further sterilized and dispensed as 7.4 GBq patient dose/vial with 2 days postformulation calibration. A peptide/metal ratio of 1.5-3.0 is essential for complexation wherein radiolabeling yields >90% are obtained minimizing free 177 Lu waste. For formulation of 7.4 GBq patient dose (2 days postproduction), even specific activity of about 555 GBq/mg was found to be adequate for the radiometal. The ready-to-use 740 MBq/mL 177 Lu-DOTA-TATE formulation with gentisic acid (1.5% w/v) is observed to be safe for human use for more than 1 week (radiochemical purity >98%) from the day of production when stored at -70°C. However, the target specificity may get affected beyond 2 days as the total peptide content for 7.4 GBq dose may exceed the critical peptide limit of 300 μg. Patient treatment carried with several batches of present formulation in diseased NET patients exhibited desired distribution at the tumor and its metastatic site. A ready

  9. 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

    -AuNP-c[RGDfK(C)], the MCF7 cell proliferation was significantly inhibited. Biokinetic studies were accomplished in athymic mice with U87MG induced tumors. The radiochemical purity for all {sup 177}Lu-RGD derivatives was 96 ± 2%. {sup 177}Lu-absorbed doses per injected activity delivered to U87MG tumors were 0.357±0.052 Gy/MBq (multimer), 0.252±0.027 Gy/MBq (dimer) and 0.112±0.018 Gy/MBq (monomer). {sup 177}Lu-labeled dimeric and multimeric RGD peptides demonstrated properties suitable for targeted radionuclide therapy and multimeric system for plasmonic photothermal therapy of tumors expressing α(v)β(3) and α(v)β(5) integrin s. (Author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-09-17

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

  11. 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

    (7 %) received calcium substitution therapy. The mean serum calcium level decreased significantly after treatment with {sup 177}Lu-octreotate, resulting in mild hypocalcaemia in about 20 % of patients. We excluded several potential causes of this hypocalcaemia, so the cause remains unknown. Serum calcium levels should be monitored after peptide receptor radionuclide therapy, and calcium substitution therapy should be initiated if appropriate. (orig.)

  12. Repeated Radionuclide therapy in metastatic paraganglioma leading to the highest reported cumulative activity of 131I-MIBG

    International Nuclear Information System (INIS)

    Ezziddin, Samer; Sabet, Amir; Ko, Yon-Dschun; Xun, Sunny; Matthies, Alexander; Biersack, Hans-Jürgen

    2012-01-01

    131 I-MIBG therapy for neuroendocrine tumours may be dose limited. The common range of applied cumulative activities is 10-40 GBq. We report the uneventful cumulative administration of 111 GBq (= 3 Ci) 131 I-MIBG in a patient with metastatic paraganglioma. Ten courses of 131 I-MIBG therapy were given within six years, accomplishing symptomatic, hormonal and tumour responses with no serious adverse effects. Chemotherapy with cisplatin/vinblastine/dacarbazine was the final treatment modality with temporary control of disease, but eventually the patient died of progression. The observed cumulative activity of 131 I-MIBG represents the highest value reported to our knowledge, and even though 12.6 GBq of 90 Y-DOTATOC were added intermediately, no associated relevant bone marrow, hepatic or other toxicity were observed. In an individual attempt to palliate metastatic disease high cumulative activity alone should not preclude the patient from repeat treatment

  13. Synthesis of DOTMP and biodistribution and imaging study of 177-Lu-DOTMP

    International Nuclear Information System (INIS)

    Deng Xinrong; Luo Zhifu; Xiang Xueqin; Li Fenglin; Fan Caiyun; Liu Zihua; Ye Zhaoyun; Li Hongyu; Chen Yang; Zhuang Ling

    2012-01-01

    Cyclen (1, 4, 7, 10-tetraazacyclododecane) and H 3 PO 3 was used to synthesis DOTMP (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-Tetraamino methylenephosphonate). 177 Lu was produced by irradiating enriched lutetium oxide ( 176 Lu 2 O 3 ) with thermal neutron flux of 2' × 10 13 n/cm 2 /S in swimming pool reactor (SPR) for 10 days. And then DOTMP was labelled by 177 Lu. The biodistribution of 177 Lu-DOTMP in model mice bearing S180 sarcoma and SPECT imaging in Japanese white rabbit were also carried out. The results showed that the total activity of 177 LuCl 3 solution obtained was 9.19 × 10 5 MBq after corresponding chemical process. According to the optimal condition of the labeling experiment, the labelling efficiency of 177 Lu-DOTMP was 99.4%. The results of biodistribution study indicated that 177 Lu-DOTMP eliminated rapidly from blood and was delivered to target bone. The radioactivity uptake was mainly in bone and less in other viscera. The results of SPECT imaging showed that the radioactivity was accumulated in bladder. 177 Lu-DOTMP was mainly excreted by kidney. The uptake of the activity in the skeleton was observed within 22 h postinjection and it became quite significant at 46 h post injection. It indicated that 177 Lu-DOTMP has good bone targeting and is worthy of further research. (authors)

  14. Neoadjuvant Treatment of Nonfunctioning Pancreatic Neuroendocrine Tumors with [177Lu-DOTA0,Tyr3]Octreotate

    NARCIS (Netherlands)

    van Vliet, Esther I.; van Eijck, Casper H.; de Krijger, Ronald R.; Nieveen van Dijkum, Elisabeth J.; Teunissen, Jaap J.; Kam, Boen L.; de Herder, Wouter W.; Feelders, Richard A.; Bonsing, Bert A.; Brabander, Tessa; Krenning, Eric P.; Kwekkeboom, Dik J.

    2015-01-01

    Pancreatic neuroendocrine tumors (NETs) are rare neoplasms for which surgery has almost the only potential for cure. When surgery is not possible because of tumor size and vascular involvement, neoadjuvant treatment with [(177)Lu-DOTA(0),Tyr(3)]octreotate ((177)Lu-octreotate) may be an option. We

  15. Study of the production of {sup 177}Lu through {sup 176}Yb (n, {gamma}) {sup 177}Yb {yields} {sup 177}Lu nuclear reaction

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Giovana Pasqualini da; Osso Junior, Joao Alberto [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)]. E-mail: gpsilva@ipen.br; jaosso@ipen.br

    2007-07-01

    The beta minus emitter {sup 177}Lu is a promising therapeutic radioisotope for the curative treatment of cancer using labelled proteins. It has a half - life of T{sub 1/2} = 6.71 day and maximum and average {beta}{sup -} energies of 421 and 133 keV, resulting in a short range of radiation in tissue. The decay is accompanied by the emission of low energy {gamma}-radiation with 208.3 keV (11%) and 113 keV (6.4%) suitable for simultaneous imaging, {sup 177}Lu can be produced by two different routes, namely, by irradiation of natural Lu{sub 2}O{sub 3} target ({sup 176}Lu, 2.6%) or enriched (in {sup 176}Lu) Lu{sub 2}O{sub 3} target, as also by irradiation of Yb target (Yb{sub 2}O{sub 3}) followed by radiochemical separation of {sup 177}Lu from Yb isotopes. The objective of this work is to study the production of {sup 177}Lu through the indirect {sup 176}Yb(n,{gamma}){sup 177}Yb {yields} {sup 177}Lu nuclear reaction. The results of the production yield of {sup 177}Lu will be shown and compared with the direct reaction. The method of choice for the chemical separation between Lu and Yb was the ion exchange, using an cation exchange resin in Cl{sup -} form and {alpha}-HIBA as eluent. Preliminary results showed a good separation of {sup 177}Lu from Yb{sub 2}O{sub 3} indirect targets. (author)

  16. [{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.

  17. Safety of multiple repeated cycles of {sup 177}Lu-octreotate in patients with recurrent neuroendocrine tumour

    Energy Technology Data Exchange (ETDEWEB)

    Yordanova, Anna; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Mayer, Karin; Brossart, Peter [University Hospital Bonn, Department of Internal Medicine 3, Bonn (Germany); Gonzalez-Carmona, Maria A.; Strassburg, Christian P. [University Hospital Bonn, Department of Internal Medicine 1, Bonn (Germany)

    2017-07-15

    Peptide receptor radionuclide therapy (PRRT) is an effective therapy in patients with a somatostatin receptor-positive neuroendocrine tumour (NET). Still unclear is how many cycles of {sup 177}Lu-octreotate can be repeated while maintaining an acceptable toxicity profile. The purpose of this study was to assess the safety of repeated PRRT in patients with recurrent NET. We retrospectively evaluated data from 15 patients treated with repeated PRRT between 2004 and 2015. The median administered activity was 63.8 GBq (range 52-96.6 GBq) in a median of 9 cycles (range 8-13 cycles). Nonhaematological and haematological toxicities were assessed from clinical reports and laboratory data. The rates of adverse events in three therapy groups were compared: during cycles 1 to 4, cycles 5 to 8, and cycles 9 to 13. Baseline laboratory assessments were also compared with data obtained at the end of treatment. The overall survival in the study patients was compared with survival data in patients who received only a baseline PRRT of three or four cycles. We observed no life-threatening adverse events (CTC-4) during {sup 177}Lu-octreotate treatment. Reversible haematological toxicity (CTC-3) occurred in two patients (13%). No CTC-3/4 nephrotoxicity was recorded. More CTC-3 adverse events were recorded in the first therapy group than in the other two groups. Furthermore, there were no significant changes in the mean values of thrombocytes, leucocytes and serum creatinine before and after therapy. However, the mean haemoglobin levels fell from 14 g/dL to 11 g/dL. Finally, compared with those patients who received three or four cycles, there was a survival benefit in patients treated with repeated PRRT (censored overall survival 85.6 vs. 69.7 months, p < 0.001). Therapy with eight or more cycles of {sup 177}Lu-octreotate was well tolerated and led to a survival benefit in patients with recurrent NET. (orig.)

  18. 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

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

    International Nuclear Information System (INIS)

    Costa, Gustavo Coelho Alves; Sa, Lidia Vasconcellos de

    2011-01-01

    This paper investigated the treatment of neuroendocrine tumors (abdominal tumors) using of 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 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

  20. 131I-MIBG and neuroendocrine tumours

    International Nuclear Information System (INIS)

    Oliva Gonzalez, Juan Perfecto; Gonzalez Gonzalez, Joaquin Jorge; Calderon Marin, Carlos Fabian

    2012-01-01

    Neuroendocrine tumours are neoplasms that arise from various tissues closely linked to the neural crest by their common embryological origin. These tumours have the ability to synthesize neurotransmitter peptides and hormones, as well as to store catecholamines. Some of these tumours express somatostatin receptors at their membranes, what have allowed nuclear medicine to be involved in their diagnosis, treatment and monitoring. Since they arise from different and varied types of tissues, these tumours have a wide range of signs and symptoms different for every one of them. These signs and symptoms mainly depend on their biochemical characteristics, given by the substances they secrete, as well as by their location, and consequently, they also depend on the place where the tumour appears, its local infiltration, and potential long-distance metastasis resulting from the tumour). Neuroendocrine tumours are diagnosed by means of nuclear medicine images, which are obtained by using different techniques and radiopharmaceuticals such as 99 mTc dimercaptosuccinic acid (DMSA(V)), 99 mTc-methoxy-isobutyl-isonitrile (MIBI), metaiodobenzylguanidine (MIBG) labelled with 131 I or 123 I ( 131 I-MIBG or 123 I -MIBG), 111 In-labelled octreotide, positron emission tomography, using 68 Ga-labelled somatostatin analogues and carcinoembryonic antigen monoclonal antibodies. Nuclear medicine uses mainly somatostatin analogues labelled with 90 Y or 177 Lu for the treatment of these tumours. This paper is aimed at showing our experience in the use of 131 I-MIBG for the diagnosis and treatment of neuroendocrine tumours.(author)

  1. Long-range transport of gaseous 131I and other radionuclides from Fukushima accident to Southern Poland

    Science.gov (United States)

    Mietelski, Jerzy W.; Kierepko, Renata; Brudecki, Kamil; Janowski, Paweł; Kleszcz, Krzysztof; Tomankiewicz, Ewa

    2014-07-01

    A serious accident at Fukushima Dai-Ichi NPP triggered radioactive emission to the atmosphere on 12 March 2011. The results of gamma spectrometric measurements of both gaseous and aerosol fraction of the air, collected in Krakow over the period from March 21 till the end of May 2011, as well as wet and dry deposition recorded from March till the end of October 2011, are presented in this paper. Krakow happened to be the first Polish location where radioactive isotopes characteristic for reactor releases, such as 131I, 132I, 129mTe, 132Te, 134Cs, 136Cs, and 137Cs, were detected. The maximum activity for aerosols equal to (5.73 ± 0.35) mBq/m3, (0.461 ± 0.041) mBq/m3 and (0.436 ± 0.038) mBq/m3 for 131I, 134Cs and 137Cs, respectively, was recorded for March 29, 2011. The data on the fallout are also given. The results of the radiochemical analysis of aerosol samples showed no traces of plutonium or americium isotopes associated with the disaster to be detected. The results of air activity concentration from Fukushima accident observed in Central Europe, Poland, in comparison to those of Chernobyl accident observed in Japan are presented and discussed. The comparison has revealed a discrepancy in the recognized relative scale of both accidents, and important difference in long distance transport of contamination, to exist. An attempt to explain the variation in the activity ratios between the aerosol fraction for 131I and 137Cs as resulting from exchange between the gaseous and aerosol fractions of 131I while the contamination had been propagating, is made.

  2. 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)

  3. Radiolabeling parameters of 177Lu-DOTA-RITUXIMAB

    International Nuclear Information System (INIS)

    Massicano, Adriana V.F.; Alcarde, Lais F.; Oliveira, Ricardo S.; Mengatti, Jair; Araujo, Elaine B. de

    2013-01-01

    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 177 LuCl 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)

  4. Preparation of (177Lu-DOTAn-PAMAM-[Nimotuzumab-F(ab’2] as a Therapeutic Radioimmunoconjugate for EGFR Overexpressed Cancer Treatment

    Directory of Open Access Journals (Sweden)

    Titis Sekar Humani

    2017-12-01

    Full Text Available Intact monoclonal antibodies with a high molecular weight tend to have a poor pharmacokinetic profile and tumor penetration, and potential for eliciting host antibody responses. F(ab’2 fragments smaller than intact monoclonal antibodies that still maintain antigen binding could solve this problem. The objective of this study was to optimize the digestion process of nimotuzumab, an anti-EGFR monoclonal antibody, into its F(ab’2 fragment and investigate its potential as a therapeutic radioimmunoconjugate. Optimal conditions for digestion of nimotuzumab to its F(ab’2 fragment were found to be 6 hours of digestion time with a pH of 3.5 and 1:100 mol ratio of pepsin to nimotuzumab. The purity of the F(ab’2-nimotuzumab was confirmed by SDS-PAGE and HPLC analysis. Prior to its labeling with lutetium-177 radionuclide, the nimotuzumab-F(ab’2 was conjugated to DOTA-PAMAM dendrimer [DOTA denotes 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid, PAMAM denotes poly(amidoamine] to form conjugate of (DOTAn-PAMAM-[nimotuzumab-F(ab’2]. Radiolabeling of DOTA-PAMAM-[nimotuzumab-F(ab’2] conjugate with 177Lu resulted in (177Lu-DOTAn-PAMAM-[nimotuzumab-F(ab’2] with radiochemical purity > 99% after purification with a PD-10 column. Further studies still need to be performed in order to confirm the potential of this radioimmunoconjugate as a radioimmunotherapeutic agent for EGFR overexpressed cancers.

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

    International Nuclear Information System (INIS)

    Hippeläinen, E; Tenhunen, M; Sohlberg, A

    2015-01-01

    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 177 Lu 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 177 Lu 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. 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)

    Sanchez G, M. F.

    2013-01-01

    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 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 ( 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 177 Lu-DOTA-Nal 3 -Octreotide ( 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 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 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 Instituto Nacional de

  7. High clinical and morphologic response using 90Y-DOTA-octreotate sequenced with 177Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours.

    Science.gov (United States)

    Kong, Grace; Callahan, Jason; Hofman, Michael S; Pattison, David A; Akhurst, Tim; Michael, Michael; Eu, Peter; Hicks, Rodney J

    2017-03-01

    Bulky disease is an adverse prognostic factor for 177 Lu-DOTA-octreotate ( 177 Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). 90 Y-DOTA-octreotate ( 90 Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than 177 Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of 90 Y-DOTATATE followed by 2-3 cycles of 177 Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq 90 Y-DOTATATE, and 21 GBq 177 Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with 90 Y -DOTATATE followed by 177 Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either agent used alone or other approved

  8. 131I Metaiodobenzylguanidine scintigraphy

    International Nuclear Information System (INIS)

    Izumi, Motomori; Morimoto, Isao; Yamashita, Shunichi; Hirayu, Hideshi; Nagataki, Shigenobu

    1988-01-01

    A newly developed radiopharmaceutical agent, 131 I-metaiodobenzylguanidine ( 131 I-MIBG) has been reported to be very useful for locating pheochromocytoma and to be specific for pheochromocytoma and safe for humans. The first 131 I-MIBG scintiscanning in Japan which has been carried out in our clinic and the analysis of clinical experience of 131 I-MIBG scanning in Japan are presented

  9. {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

  10. Indigenous development of TBq levels of "1"7"7Lu radioisotope production at RPhD for nuclear medicine applications - a successful venture

    International Nuclear Information System (INIS)

    Chakraborty, Sudipta; Vimalnath, K.V.; Dash, Ashutosh

    2017-01-01

    Lutetium-177 ("1"7"7Lu) has emerged as a potential radionuclide during last decade for the development of radionuclide therapy owing to its favorable nuclear decay characteristics (T_1_/_2=6.65 d, E_β_(_m_a_x) = 0.497 MeV, E_γ = 113 keV (6.4%) and 208 keV (11%)). The long half-life of this promising radioisotope offering distinct logistical advantage and feasibility of its large-scale production in medium flux Dhruva research reactor contributed to its success story

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

    International Nuclear Information System (INIS)

    Sheng Feng; Jia Bing; Wang Fan; He Weiwei; Liu Zhaofei; Zhao Huiyun

    2008-01-01

    177 Lu-DOTA-Bz-Cys-RGD dimer and 177 Lu-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 177 Lu-DOTA-Bz-Cys- RGD dimer is higher than 177 Lu-DTPA-Bz-Cys-RGD dimer. The uptake of 177 Lu-DTPA-Bz-Cys- RGD dimer in other tissues is significantly higher than that of 177 Lu-DOTA-Bz-Cys-RGD dimer at 4 h postinjection, except for blood and spleen. The in vivo stability of 177 Lu-DOTA-Bz-Cys-RGD dimer is much better than 177 Lu-DTPA-Bz-Cys-RGD dimer. Bz-DOTA is an ideal bifunctional chelator for 177 Lu labeling of RGD dimer. (authors)

  12. Time- and dose rate-related effects of internal 177Lu exposure on gene expression in mouse kidney tissue

    International Nuclear Information System (INIS)

    Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Spetz, Johan; Helou, Khalil; Forssell-Aronsson, Eva

    2014-01-01

    Introduction: The kidneys are the dose-limiting organs in some radionuclide therapy regimens. However, the biological impact of internal exposure from radionuclides is still not fully understood. The aim of this study was to examine the effects of dose rate and time after i.v. injection of 177 LuCl 3 on changes in transcriptional patterns in mouse kidney tissue. Methods: To investigate the effect of dose rate, female Balb/c nude mice were i.v. injected with 11, 5.6, 1.6, 0.8, 0.30, and 0 MBq of 177 LuCl 3 , and killed at 3, 6, 24, 48, 168, and 24 hours after injection, respectively. Furthermore, the effect of time after onset of exposure was analysed using mice injected with 0.26, 2.4, and 8.2 MBq of 177 LuCl 3 , and killed at 45, 90, and 140 days after injection. Global transcription patterns of irradiated kidney cortex and medulla were assessed and enriched biological processes were determined from the regulated gene sets using Gene Ontology terms. Results: The average dose rates investigated were 1.6, 0.84, 0.23, 0.11 and 0.028 mGy/min, with an absorbed dose of 0.3 Gy. At 45, 90 and 140 days, the absorbed doses were estimated to 0.3, 3, and 10 Gy. In general, the number of differentially regulated transcripts increased with time after injection, and decreased with absorbed dose for both kidney cortex and medulla. Differentially regulated transcripts were predominantly involved in metabolic and stress response-related processes dependent on dose rate, as well as transcripts associated with metabolic and cellular integrity at later time points. Conclusion: The observed transcriptional response in kidney tissue was diverse due to difference in absorbed dose, dose rate and time after exposure. Nevertheless, several transcripts were significantly regulated in all groups despite differences in exposure parameters, which may indicate potential biomarkers for exposure of kidney tissue

  13. Comparison of activity measurements of 131I and 99mTc radionuclides administered in nuclear medicine services of Porto Alegre

    International Nuclear Information System (INIS)

    Alabarse, Frederico Gil.; Santos, Carlos Eduardo Lima dos

    2005-01-01

    A programme for the comparison of activity measurements of radionuclides administered to patients in Nuclear Medicine Services, for the purpose of diagnosis or therapy, is being conducted under the coordination of the Radioprotection and Dosimetry Institute of the Brazilian Nuclear Energy Commission, IRD/CNEN. In the present work, measurements of the activity of samples of 131 I and 99 mTc were conducted in the dose calibrators of the Nuclear Medicine Services of the city of Porto Alegre, in the period from June to September 2004. The results were analysed to evaluate the compliance with the Brazilian regulation and were also compared to data available in the literature for the cities of Rio de Janeiro and Brasilia. The performance of the activity meters in Porto Alegre is shown to be very good, which contributes to the radiological protection of patients submitted to diagnosis or therapy with radiopharmaceuticals. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2010-10-15

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

  15. Tumoral fibrosis effect on the radiation absorbed dose of 177Lu-Tyr3-octreotate-gold nanoparticles and 177Lu-Tyr3-octreotate radiopharmaceuticals

    International Nuclear Information System (INIS)

    Zambrano R, O. D.

    2015-01-01

    In this work was comparatively evaluated the effect of tumoral fibrosis in the radiation absorbed dose of the radiopharmaceutical 177 Lu-Tyr 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 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 ( 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). To this spectrum

  16. Production of non carrier added (n.c.a.) {sup 177}Lu for radiopharmaceutical applications

    Energy Technology Data Exchange (ETDEWEB)

    Barkhausen, Christoph

    2011-09-06

    The goal of this dissertation was the development of a process to produce non carrier added {sup 177}Lu at the FRM II. For this purpose, preparative chromatographic methods were evaluated and applied. The highest quality of the nuclide which could only be achieved through a complex chemical process, has been already been proven by clinical studies to be very advantageous. The process has been built up in a hot cell as a semi-automated process and is now being adapted to the requirements of the 'Arzneimittelgesetz' in order to establish n.c.a. {sup 177}Lu as a pharmaceutical product.

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

    International Nuclear Information System (INIS)

    Lopez Bularte, A.C.; Nevares, N.N.; Zapata, A.M.; Perez, J.H.; Crudo, J.L.; Puerta Yepes, N.; Rojo, A.M.

    2010-01-01

    The aim of this work is to obtain 177 Lu-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) 177 LuCl 3 of an intermediate level of Ae (between 6.36 to 17.95 Ci/mg of 176 Lu) ) and also to perform in vitro and in vivo stability tests, dose calculation in normal mice and its extrapolation to a human model. (authors) [es

  18. 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

    and the activity, which depends on the collimator type, the utilized energy windows and the applied scatter correction techniques. In this study, energy window subtraction-based scatter correction methods are compared experimentally and quantitatively. MATERIALS AND METHODS: (177)Lu SPECT images of a phantom...... technique, the measured ratio was close to the real ratio, and the differences between spheres were small. CONCLUSION: For quantitative (177)Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated...

  19. 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

  20. 177Lu-DKFZ-PSMA-617 therapy in metastatic castration resistant prostate cancer: safety, efficacy, and quality of life assessment

    International Nuclear Information System (INIS)

    Yadav, Madhav Prasad; Ballal, Sanjana; Tripathi, Madhavi; Damle, Nishikant Avinash; Bal, Chandrasekhar; Sahoo, Ranjit Kumar; Seth, Amlesh

    2017-01-01

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

  1. 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

  2. Synergistic anti-cancer response to chemotherapy and 177Lu-labelled APOMABR radioimmunotherapy in a preclinical model of lung cancer

    International Nuclear Information System (INIS)

    Staudacher, A.H.; Brown, M.P.

    2015-01-01

    Full text of publication follows. Aim: We have identified a murine monoclonal antibody (APOMAB R ) which targets the La antigen. La is a ribonucleoprotein which is over-expressed in malignancy and is only accessible to antibody binding when tumour cells die, making APOMAB R a dead tumour cell-specific marker. We hypothesise that APOMAB R radio-labelled with the β-particle emitting radionuclide Lutetium-177 ( 177 Lu) will be an effective anti-tumour treatment in vivo, particular after chemotherapy, as the targeting of radio-labelled APOMAB R specifically to dead tumour cells within the tumour tissue will result in the surrounding viable tumour cells being irradiated with a therapeutic dose of β-radiation. Material and Methods: The binding of APOMAB R to viable and dead murine Lewis Lung cells (LL2) was examined in vitro by flow cytometry. Subsequently, C57Bl/6 mice bearing syngeneic LL2 tumours were treated with chemotherapy (gemcitabine/cisplatin) and the tumour uptake of biotinylated APOMAB R was determined. We then administered escalating activities of 177 Lu-labelled APOMAB R or a 177 Lu-labelled iso-type control antibody either alone or 24 hours after chemotherapy and monitored tumour growth and survival. We also analysed the bio-distribution of 177 Lu-labelled APOMAB R in LL2 tumour-bearing mice which had or had not been treated with chemotherapy to determine whether the uptake of APOMAB R after chemotherapy treatment was tumour-specific. Results: In vitro analysis revealed that APOMAB R did not bind viable LL2 cells, but bound with high avidity to cisplatin-treated, dead LL2 cells. Chemotherapy increased tumour cell death in vivo, and was associated with increased tumour uptake of APOMAB R compared to LL2 tumour-bearing mice that did not receive chemotherapy. Administration of escalating doses of 177 Lu-labelled APOMAB R alone to tumour-bearing mice was well tolerated but showed only modest anti-tumour activity which was comparable to the response seen

  3. Determination of the physiological root activity of fruit trees by means of the radionuclide 131I. 2

    International Nuclear Information System (INIS)

    Reckruehm, I.

    1976-01-01

    The rate of climb of the radionuclide per 1 m of stem vascular height was found to be dependent on the time of application; it came up to six to seven hours if applied in the morning, and 17 hours if applied in the evening. Limited information concerning the xylem transport activity was obtained through measuring the activity of a boring sample of stem fresh matter. Autoradiographic stem analysis provided the information most suitable for determining the transport routes in the stem. The analysis revealed that with increasing stem height the width of the radionuclide-labelled xylem is increasing 4.5 fold in proportion to the width when entering the stem. Beside the vertical climb there is some limited horizontal spread of the nuclide as well. (author)

  4. Preparation and preclinical evaluation of (177)Lu-nimotuzumab targeting epidermal growth factor receptor overexpressing tumors

    Czech Academy of Sciences Publication Activity Database

    Beckford, Denis R.; Eigner, Sebastian; Eigner-Henke, Kateřina; Lebeda, Ondřej; Melichar, František; Beran, Miloš

    2012-01-01

    Roč. 39, č. 1 (2012), s. 3-13 ISSN 0969-8051 R&D Projects: GA MŠk 2B06165 Institutional research plan: CEZ:AV0Z10480505 Keywords : Radioimmunotherapy * Nimotuzumab * (177)Lu * Monoclonal antibody Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 2.517, year: 2012

  5. Quantitative 177Lu-SPECT/CT imaging and validation of a commercial dosimetry software

    International Nuclear Information System (INIS)

    D'Ambrosio, L.; Aloj, L.; Morisco, A.; Aurilio, M.; Prisco, A.; Di Gennaro, F.; Lastoria, S.; Madesani, D.

    2015-01-01

    Full text of publication follows. Aim: 3D dosimetry is an appealing yet complex application of SPECT/CT in patients undergoing radionuclide therapy. In this study we have developed a quantitative imaging protocol and we have validated commercially available dosimetry software (Dosimetry Tool-kit Package, GE Heathcare) in patients undergoing 177 Lu-DOTATATE therapy. Materials and methods: dosimetry tool-kit uses multi SPECT/CT and/or WB planar datasets for quantifying changes in radiopharmaceutical uptake over time to determine residence times. This software includes tools for performing reconstruction of SPECT/CT data, registration of all scans to a common reference, segmentation of the different organs, creating time activity curves, curve fitting and calculation of residence times. All acquisitions were performed using a hybrid dual-head SPECT-CT camera (Discovery 670, GE Heathcare) equipped with medium energy collimator using a triple-energy window. SPECT images were reconstructed using an iterative reconstruction algorithm with attenuation, scatter and collimator depth-dependent three-dimensional resolution recovery correction. Camera sensitivity and dead time were evaluated. Accuracy of activity quantification was performed on a large homogeneous source with addition of attenuating/scattering medium. A NEMA/IEC body phantom was utilized to measure the recovery coefficient that the software does not take into account. The residence times for organs at risk were calculated in five patients. OLINDA-EXM software was used to calculate absorbed doses. Results: 177 Lu-sensitivity factor was 13 counts/MBq/s. Dead time was <3% with 1.11 GBq in the field of view. The measured activity was consistent with the decay-corrected calibrated activity for large volumes (>100 cc). The recovery coefficient varied from 0.71 (26.5 ml) to 0.16 (2.5 ml) in the absence of background activity and from 0.58 to 0.13 with a source to background activity concentration ratio 20:1. The

  6. Radionuclides used in nuclear medicine ({sup 131}I, {sup 99m}Tc e {sup 99}Tc) in sewage system and in the marine environment of Rio de Janeiro city, RJ, Brazil; Radionuclideos usados em medicina nuclear ({sup 131}I, {sup 99m}Tc e {sup 99}Tc) no sistema de esgoto e no ambiente marinho da cidade do Rio de Janeiro, RJ

    Energy Technology Data Exchange (ETDEWEB)

    Sousa, Daniele Santos de

    2014-08-01

    The nuclear medicine is a specialty that uses radioisotopes for diagnostic or therapeutic purpose. In Brazil there are around 340 Nuclear Medicine Services (NMS), 27 of them, are located in the city of Rio de Janeiro. The most widely used radionuclides in the country are {sup 131}I and {sup 99m}Tc. The radionuclide {sup 99m}Tc decays to {sup 99}Tc, which is a beta emitter with a long half-life (10{sup 5} years). The aim of this study is to perform a survey to estimate the {sup 131}I and {sup 99}Tc discharged levels at the Canal do Cunha, the main pathways for environmental dispersion and evaluate the radiological impact to non-human biota and to the populations exposed to these radionuclides. The Alegria Station receives sewage from most clinics of Rio de Janeiro mid was therefore chosen as a study case. The station receives approximately 4.50 x 10{sup 5} Bq/year of {sup 99}Tc e 7.12 x 10{sup 12} Bq/year of {sup 131}I. After passing through all stages of treatment, the effluent is discharged into the Canal do Cunha and flows into the Guanabara Bay. To assess the radiological impact of these radionuclide discharges, a comparative study was made considering three computational models: the CROM, which is based on a model of the International Atomic Energy Agency (IAEA), the PC-CREAM, widely used by the European Union and the GENII, which is the most widely used model in the United States. Two exposure scenarios were considered: 1 - people that bathe directly in the discharge of the effluent; 2 - community living 1200 meters from the discharge point, bathing in the river and consuming local fish. Concentration and doses values for the scenarios according to the applicability of each computer code were estimated. The dose values at the discharge point were 7.47 x 10{sup -6}mSv for {sup 131}I and 2.87 x 10{sup -14} mSv for {sup 99}Tc, while for scenario II the value of the total dose was approximately 10{sup -1} mSv/year for {sup 131}I and 10{sup -10} mSv/year for {sup

  7. 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

  8. Correlations of CTLA-4 exon-1 49 A/G and promoter region 318C/T polymorphisms with the therapeutic efficacy of 131 I radionuclide in graves' disease in Chinese Han population.

    Science.gov (United States)

    Han, Xin-Rui; Wen, Xin; Wang, Shan; Fan, Shao-Hua; Zhuang, Juan; Wang, Yong-Jian; Zhang, Zi-Feng; Li, Meng-Qiu; Hu, Bin; Shan, Qun; Sun, Chun-Hui; Bao, Ya-Xing; Wu, Dong-Mei; Lu, Jun; Zheng, Yuan-Lin

    2017-08-04

    Graves' disease is an autoimmune process in which the thyroid gland is triggered by autoantibodies, resulting in hyperthyroidism. The purpose of the present study is to elucidate whether exon-1 49 A/G and promoter region 318C/T polymorphisms in the CTLA-4 gene. This study consisted of 653 eligible patients with Graves' disease. After receiving 131I radionuclide therapy, these patients were classified into the remission and non-remission groups. A logistic regression-based model was used to analyze independent factors affecting the patient response to 131I radionuclide therapy. The results showed that CTLA-4 49 A/G was closely related to the efficacy of 131 I treatment for Graves' disease (AG + GG vs. AA: OR = 6.543, 95%CI = 2.611 ∼ 16.40, P Graves' disease. Logistic regression analysis indicated that thyroid weight (OR = 0.963, 95%CI = 0.944 ∼ 0.982, P Graves' disease. These data indicated that CTLA-4 exon-1 49 A/G polymorphism may be associated with patient response to radionuclide 131 I therapy in Graves' disease. © 2017 Wiley Periodicals, Inc.

  9. 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.

  10. 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.

  11. Transcriptional response of kidney tissue after 177Lu-octreotate administration in mice

    International Nuclear Information System (INIS)

    Schüler, Emil; Rudqvist, Nils; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

    2014-01-01

    Introduction: The kidneys are one of the main dose limiting organs in 177 Lu-octreotate therapy of neuroendocrine tumors. Therefore, biomarkers for radiation damage would be of great importance in this type of therapy. The purpose of this study was to investigate the absorbed dose dependency on early transcriptional changes in the kidneys from 177 Lu-octreotate exposure. Methods: Female Balb/c nude mice were i.v. injected with 1.3, 3.6, 14, 45 or 140 MBq 177 Lu-octreotate. The animals were killed 24 h after injection followed by excision of the kidneys. The absorbed dose to the kidneys ranged between 0.13 and 13 Gy. Total RNA was extracted from separated renal tissue samples, and applied to Illumina MouseRef-8 Whole-Genome Expression Beadchips to identify regulated transcripts after irradiation. Nexus Expression 2.0 and Gene Ontology terms were used for data processing and to determine affected biological processes. Results: Distinct transcriptional responses were observed following 177 Lu-octreotate administration. A higher number of differentially expressed transcripts were observed in the kidney medulla (480) compared to cortex (281). In addition, 39 transcripts were regulated at all absorbed dose levels in the medulla, compared to 32 in the cortex. Three biological processes in the cortex and five in the medulla were also shared by all absorbed dose levels. Strong association to metabolism was found among the affected processes in both tissues. Furthermore, an association with cellular and developmental processes was prominent in kidney medulla, while transport and immune response were prominent in kidney cortex. Conclusion: Specific biological and dose-dependent responses were observed in both tissues. The number of affected transcripts and biological processes revealed distinct response differences between the absorbed doses delivered to the tissues

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

    International Nuclear Information System (INIS)

    Rodriguez C, J.; Murphy, C.A. de; Pedraza L, M.; Ferro F, G.; Murphy S, E.

    2006-01-01

    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 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 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 177 Lu-DOTA-TATE will act as expected in man considering its kidney radiotoxicity. (Author)

  13. Evaluation of the cell death mechanisms activated by the radiopharmaceutical 177Lu-DOTA-anti-CD20 in a dose range of 1 to 5 Gy

    International Nuclear Information System (INIS)

    Azorin V, E.P.; Rojas C, E. L.; Martinez V, B. E.; Ramos B, J. C.; Jimenez M, N. P.; Ferro F, G.

    2016-10-01

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

  14. Monte Carlo simulation of radiation transport and dose deposition from locally released gold nanoparticles labeled with 111In, 177Lu or 90Y incorporated into tissue implantable depots

    Science.gov (United States)

    Lai, Priscilla; Cai, Zhongli; Pignol, Jean-Philippe; Lechtman, Eli; Mashouf, Shahram; Lu, Yijie; Winnik, Mitchell A.; Jaffray, David A.; Reilly, Raymond M.

    2017-11-01

    Permanent seed implantation (PSI) brachytherapy is a highly conformal form of radiation therapy but is challenged with dose inhomogeneity due to its utilization of low energy radiation sources. Gold nanoparticles (AuNP) conjugated with electron emitting radionuclides have recently been developed as a novel form of brachytherapy and can aid in homogenizing dose through physical distribution of radiolabeled AuNP when injected intratumorally (IT) in suspension. However, the distribution is unpredictable and precise placement of many injections would be difficult. Previously, we reported the design of a nanoparticle depot (NPD) that can be implanted using PSI techniques and which facilitates controlled release of AuNP. We report here the 3D dose distribution resulting from a NPD incorporating AuNP labeled with electron emitters (90Y, 177Lu, 111In) of different energies using Monte Carlo based voxel level dosimetry. The MCNP5 Monte Carlo radiation transport code was used to assess differences in dose distribution from simulated NPD and conventional brachytherapy sources, positioned in breast tissue simulating material. We further compare these dose distributions in mice bearing subcutaneous human breast cancer xenografts implanted with 177Lu-AuNP NPD, or injected IT with 177Lu-AuNP in suspension. The radioactivity distributions were derived from registered SPECT/CT images and time-dependent dose was estimated. Results demonstrated that the dose distribution from NPD reduced the maximum dose 3-fold when compared to conventional seeds. For simulated NPD, as well as NPD implanted in vivo, 90Y delivered the most homogeneous dose distribution. The tumor radioactivity in mice IT injected with 177Lu-AuNP redistributed while radioactivity in the NPD remained confined to the implant site. The dose distribution from radiolabeled AuNP NPD were predictable and concentric in contrast to IT injected radiolabeled AuNP, which provided irregular and temporally variant dose distributions

  15. Radiolabeled Antibody Fragment for Preparation of (177Lu-DOTAm-PAMAM G3.0-F(ab’2 trastuzumab as a Radiopharmaceutical for Cancer Therapy

    Directory of Open Access Journals (Sweden)

    R.D. Haryuni

    2017-06-01

    Full Text Available Several radiolabeled monoclonal antibodies (mAbs have been used as radioimmunotherapy (RIT agents for cancer therapy. The use of mAbs as RIT agents is due to their ability to carry effectors, in the form of radionuclides which emit alpha (α particles, beta (β particles, or auger electrons, and bind specifically to cancer expressed receptor. This paper reports the preparation of radiolabelled trastuzumab in form of (177Lu-DOTAm-PAMAM G3-F(ab'2-trastuzumab, which will be expected as a potential RIT agent for therapy of breast cancer overexpressed human epidermal growth factor receptor 2 (HER2. Due to its reduced molecular weight, the use of F(ab'2-trastuzumab on the aforementioned RIT agent candidate is expected to reach its target much faster compared to the intact trastuzumab. Meanwhile, the role of PAMAM G3 is to increase the specific activity of the radiotherapeutic agent of Lu-177 due to the ability of its 32 –NH2 functional groups that are able to bind many DOTAs (£ 31 which in turn can bind a large number of 177Lu. The preparation was initiated by fragmentation of trastuzumab using pepsin enzyme in 0.02 M acetic acid buffer with a pH of 4.5 to produce F(ab'2-trastuzumab with a purity of 95 % after purification with PD-10 column. The F(ab'2-trastuzumab was then reacted with succinimidyl 4-(N-maleimidomethyl cyclohexane-1-carboxylate (SMCC to produce SMCC-F(ab'2-trastuzumab. The next reaction was to conjugate SMCC-F(ab'2-trastuzumab with DOTA-PAMAM G3.0-SH, which was prepared by reaction NHS-DOTA with PAMAM G3.0 and followed by reacting it with 2-iminothiolane to give (DOTAm-PAMAM G3.0-F(ab'2-trastuzumab. Finally, the (DOTAm-PAMAM G3.0-F(ab'2-trastuzumab was radiolabelled with 177Lu to produce (177Lu-DOTAm-PAMAM G3.0-F(ab'2-trastuzumab, resulting in a radiochemical purity of 98 % after purification with PD-10 column.Received: 31 October 2015; Revised: 30 June 2016; Accepted: 25 September 2016

  16. Radionuclides used in nuclear medicine (131I, 99mTc e 99Tc) in sewage system and in the marine environment of Rio de Janeiro city, RJ, Brazil

    International Nuclear Information System (INIS)

    Sousa, Daniele Santos de

    2014-01-01

    The nuclear medicine is a specialty that uses radioisotopes for diagnostic or therapeutic purpose. In Brazil there are around 340 Nuclear Medicine Services (NMS), 27 of them, are located in the city of Rio de Janeiro. The most widely used radionuclides in the country are 131 I and 99m Tc. The radionuclide 99m Tc decays to 99 Tc, which is a beta emitter with a long half-life (10 5 years). The aim of this study is to perform a survey to estimate the 131 I and 99 Tc discharged levels at the Canal do Cunha, the main pathways for environmental dispersion and evaluate the radiological impact to non-human biota and to the populations exposed to these radionuclides. The Alegria Station receives sewage from most clinics of Rio de Janeiro mid was therefore chosen as a study case. The station receives approximately 4.50 x 10 5 Bq/year of 99 Tc e 7.12 x 10 12 Bq/year of 131 I. After passing through all stages of treatment, the effluent is discharged into the Canal do Cunha and flows into the Guanabara Bay. To assess the radiological impact of these radionuclide discharges, a comparative study was made considering three computational models: the CROM, which is based on a model of the International Atomic Energy Agency (IAEA), the PC-CREAM, widely used by the European Union and the GENII, which is the most widely used model in the United States. Two exposure scenarios were considered: 1 - people that bathe directly in the discharge of the effluent; 2 - community living 1200 meters from the discharge point, bathing in the river and consuming local fish. Concentration and doses values for the scenarios according to the applicability of each computer code were estimated. The dose values at the discharge point were 7.47 x 10 -6 mSv for 131 I and 2.87 x 10 -14 mSv for 99 Tc, while for scenario II the value of the total dose was approximately 10 -1 mSv/year for 131 I and 10 -10 mSv/year for 99 Tc, and fish consumption is the main responsible for the dose. An analysis by gamma

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

    Science.gov (United States)

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

    2015-01-01

    The aim of this study is to assess the effectiveness of Radiosynovectomy (RSV) using (177)Lu-labeled hydroxyapatite ((177)Lu-HA) in the treatment of painful synovitis and recurrent joint effusion of knee joints in rheumatoid arthritis (RA). Ten patients, diagnosed with RA and suffering from chronic painful resistant synovitis of the knee joints were referred for RSV. The joints were treated with 333 ± 46 MBq of (177)Lu-HA particles administered intra-articularly. Monitoring of activity distribution was performed by static imaging of knee joint and whole-body gamma imaging. The patients were evaluated clinically before RSV and at 6 months after the treatment by considering the pain improvement from baseline values in terms of a 100-point visual analog scale (VAS), the improvement of knee flexibility and the pain remission during the night. RSV response was classified as poor (VAS body scan. Static scans of the joint at 1 month revealed complete retention of (177)Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those with more advanced changes (Steinbrocker's Grades III and IV) in terms of VAS improvement (75% vs. 45.8%) (P level was not different before and after RSV. RSV side-effects assessed for the whole follow-up period were minor and not significant. RSV with (177)Lu-HA was safe and effective in patients with knee joint chronic painful synovitis of rheumatoid origin. It exhibited significant therapeutic effect after 6 months follow-up period with no significant side-effects. The preliminary investigations reveal that (177)Lu-labeled HA particles hold considerable promise as a cost-effective agent for RSV. More elaborate and

  18. High clinical and morphologic response using {sup 90}Y-DOTA-octreotate sequenced with {sup 177}Lu-DOTA-octreotate induction peptide receptor chemoradionuclide therapy (PRCRT) for bulky neuroendocrine tumours

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Grace; Callahan, Jason; Pattison, David A.; Akhurst, Tim; Eu, Peter [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); Hofman, Michael S. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, Department of Medicine, Parkville (Australia); Michael, Michael [Peter MacCallum Cancer Centre, Division of Cancer Medicine, Neuroendocrine Tumour Unit, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia); Hicks, Rodney J. [Peter MacCallum Cancer Centre, Centre for Cancer Imaging, Melbourne, VIC (Australia); The University of Melbourne, The Sir Peter MacCallum Department of Oncology, Parkville (Australia)

    2017-03-15

    Bulky disease is an adverse prognostic factor for {sup 177}Lu-DOTA-octreotate ({sup 177}Lu-DOTATATE) peptide receptor radionuclide therapy (PRRT). {sup 90}Y-DOTA-octreotate ({sup 90}Y-DOTATATE) has theoretical advantages in this setting but may less effectively treat co-existent smaller deposits and have higher toxicity than {sup 177}Lu-DOTATATE. The aim of this study was to assess the efficacy and safety of using these agents sequentially. We reviewed patients (pts) with at least one lesion of a transaxial diameter >4 cm who completed 1-2 cycles of {sup 90}Y-DOTATATE followed by 2-3 cycles of {sup 177}Lu-DOTATATE, with treatment empirically adapted to disease size and burden in individual patients. Data collected included morphological and molecular imaging response, toxicity, and progression-free and overall survival. Twenty-six pts (17 men; aged 27-74 years) received a median cumulative activity of 6.5 GBq {sup 90}Y-DOTATATE, and 21 GBq {sup 177}Lu-DOTATATE. All but one received radiosensitising chemotherapy. Adverse prognostic factors included ENETS grade 2 or 3 in 58 %, and FDG-avid disease in 73 %. Nineteen pts treated for progressive disease had stabilisation (37 %) or regression on CT (42 % partial response, 21 % minor response), with a mean 59 % (8-99 %) reduction in disease burden. All seven pts treated for uncontrolled symptoms reported improvement during PRRT with 4/7 having complete symptom resolution at 3 months. Eight patients had grade 3/4 lymphopaenia, and two patients grade 3/4 thrombocytopaenia without significant hepatic or renal toxicity. Median survival was not reached after a median follow-up of 35 months. Median progression-free survival was 33 months. PRCRT with {sup 90}Y -DOTATATE followed by {sup 177}Lu-DOTATATE in individualised regimens achieved high clinical and morphological response in patients with bulky tumours. Despite lack of a control arm, the efficacy of this treatment approach appears higher than reported results with either

  19. Antitenascin antibody 81C6 armed with {sup 177}Lu: in vivo comparison of macrocyclic and acyclic ligands

    Energy Technology Data Exchange (ETDEWEB)

    Yordanov, Alexander T. [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States); Hens, Marc [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States); Pegram, Charles [Department of Pathology, 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. [Department of Radiology, Duke University Medical Center Durham, NC 27710 (United States)]. E-mail: zalut001@mc.duke.edu

    2007-02-15

    Introduction: When labeled with iodine-131, the antitenascin monoclonal antibody (mAb) 81C6 has shown promise as a targeted radiotherapeutic in patients with brain tumors. Because of its more favorable {gamma}-ray properties, lutetium-177 might be a better low-energy {beta}-emitter for this type of therapy. Materials and Methods: Chimeric 81C6 (ch81C6) was labeled with {sup 177}Lu using the acyclic 1B4M ligand and the macrocyclic ligands NHS-DOTA and MeO-DOTA and evaluated for binding to tenascin. Three paired-label tissue distribution experiments were performed in normal mice receiving one of the {sup 177}Lu-labeled immunoconjugates plus {sup 125}I-labeled ch81C6 labeled using Iodogen. Paired-label experiments in athymic mice bearing subcutaneous D54 MG human glioma xenografts were done to directly compare the biodistribution of ch81C6-1B4M-{sup 177}Lu and {sup 125}I-labeled ch81C6, and ch81C6-MeO-DOTA-{sup 177}Lu and {sup 125}I-labeled ch81C6. Similar comparisons were done using murine (mu) instead of ch81C6. The primary parameter utilized for evaluation was the {sup 177}Lu/{sup 125}I uptake ratio in each tissue. Results: In the studies performed in normal mice, the NHS-DOTA ligand yielded the highest {sup 177}Lu/{sup 125}I uptake ratios in tissues indicative of loss of label from the chelate; for this reason, only 1B4M and MeO-DOTA were evaluated further. The {sup 177}Lu/{sup 125}I ratio in bone increased gradually with time for the chimeric conjugates; however, there were no significant differences between ch81C6-1B4M-DTPA-{sup 177}Lu and ch81C6-MeO-DOTA-{sup 177}Lu. In contrast, mu81C6-1B4M-DTPA-{sup 177}Lu and mu81C6-MeO-DOTA-{sup 177}Lu showed a more dramatic increase in the {sup 177}Lu/{sup 125}I ratio in bone - from 2.4{+-}0.3 and 1.7{+-}0.2 at Day 1 to 8.5{+-}1.1 and 4.2{+-}0.5 at Day 7, respectively. Conclusion: With these antitenascin constructs, the nature of the mAb had a profound influence on the relative degree of loss of {sup 177}Lu from these

  20. 177Lu-labeled HPMA copolymers utilizing cathepsin B and S cleavable linkers: Synthesis, characterization and preliminary in vivo investigation in a pancreatic cancer model

    International Nuclear Information System (INIS)

    Ogbomo, Sunny M.; Shi, Wen; Wagh, Nilesh K.; Zhou, Zhengyuan; Brusnahan, Susan K.; Garrison, Jered C.

    2013-01-01

    Introduction: A major barrier to the advancement of therapeutic nanomedicines has been the non-target toxicity caused by the accumulation of the drug delivery systems in organs associated with the reticuloendothelial system, particularly the liver and spleen. Herein, we report the development of peptide based metabolically active linkers (MALs) that are enzymatically cleaved by cysteine cathepsin B and S, two proteases highly expressed in the liver and spleen. The overall goal of this approach is to utilize the MALs to lower the non-target retention and toxicity of radiolabeled drug delivery systems, thus resulting in higher diagnostic and radiotherapeutic efficacy. Methods: In this study three MALs (MAL0, MAL1 and MAL2) were investigated. MAL1 and MAL2 are composed of known substrates of cathepsin B and S, respectively, while MAL0 is a non-cleavable control. Both MAL1 and MAL2 were shown to undergo enzymatic cleavage with the appropriate cathepsin protease. Subsequent to conjugation to the HPMA copolymer and radiolabeling with 177 Lu, the peptide–polymer conjugates were renamed 177 Lu-metabolically active copolymers ( 177 Lu-MACs) with the corresponding designations: 177 Lu-MAC0, 177 Lu-MAC1 and 177 Lu-MAC2. Results: In vivo evaluation of the 177 Lu-MACs was performed in an HPAC human pancreatic cancer xenograft mouse model. 177 Lu-MAC1 and 177 Lu-MAC2 demonstrated 3.1 and 2.1 fold lower liver retention, respectively, compared to control ( 177 Lu-MAC0) at 72 h post-injection. With regard to spleen retention, 177 Lu-MAC1 and 177 Lu-MAC2 each exhibited a nearly fourfold lower retention, relative to control, at the 72 h time point. However, the tumor accumulation of the 177 Lu-MAC0 was two to three times greater than 177 Lu-MAC1 and 177 Lu-MAC2 at the same time point. The MAL approach demonstrated the capability of substantially reducing the non-target retention of the 177 Lu-labeled HPMA copolymers. Conclusions: While further studies are needed to optimize the

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

    International Nuclear Information System (INIS)

    Hassan Yousefnia; Amir Reza Jalilian; Ali Bahrami-Samani; Simindokht Shirvani-Arani; Mohammad Ghannadi-Maragheh; Azim Arbabi; Edalat Radfar

    2011-01-01

    Rituximab was successively labeled with 177 Lu-lutetium chloride. 177 Lu chloride was obtained by thermal neutron flux (4 x 1013 n cm -2 s -1 ) of natural Lu 2 O 3 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 CH 2 Cl 2 . 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 177 Lu-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)

  2. PRRT genomic signature in blood for prediction of 177Lu-octreotate efficacy.

    Science.gov (United States)

    Bodei, Lisa; Kidd, Mark S; Singh, Aviral; van der Zwan, Wouter A; Severi, Stefano; Drozdov, Ignat A; Cwikla, Jaroslaw; Baum, Richard P; Kwekkeboom, Dik J; Paganelli, Giovanni; Krenning, Eric P; Modlin, Irvin M

    2018-07-01

    Peptide receptor radionuclide therapy (PRRT) utilizes somatostatin receptor (SSR) overexpression on neuroendocrine tumors (NET) to deliver targeted radiotherapy. Intensity of uptake at imaging is considered related to efficacy but has low sensitivity. A pretreatment strategy to determine individual PRRT response remains a key unmet need. NET transcript expression in blood integrated with tumor grade provides a PRRT predictive quotient (PPQ) which stratifies PRRT "responders" from "non-responders". This study clinically validates the utility of the PPQ in NETs. The development and validation of the PPQ was undertaken in three independent 177 Lu-PRRT treated cohorts. Specificity was tested in two separate somatostatin analog-treated cohorts. Prognostic value of the marker was defined in a cohort of untreated patients. The developmental cohort included lung and gastroenteropancreatic [GEP] NETs (n = 72) from IRST Meldola, Italy. The majority were GEP (71%) and low grade (86% G1-G2). Prospective validation cohorts were from Zentralklinik Bad Berka, Germany (n = 44), and Erasmus Medical Center, Rotterdam, Netherlands (n = 42). Each cohort included predominantly well differentiated, low grade (86-95%) lung and GEP-NETs. The non-PRRT comparator cohorts included SSA cohort I, n = 28 (100% low grade, 100% GEP-NET); SSA cohort II, n = 51 (98% low grade; 76% GEP-NET); and an untreated cohort, n = 44 (64% low grade; 91% GEP-NET). Baseline evaluations included clinical information (disease status, grade, SSR) and biomarker (CgA). NET blood gene transcripts (n = 8: growth factor signaling and metabolism) were measured pre-therapy and integrated with tumor Ki67 using a logistic regression model. This provided a binary output: "predicted responder" (PPQ+); "predicted non-responder" (PPQ-). Treatment response was evaluated using RECIST criteria [Responder (stable, partial and complete response) vs Non-Responder)]. Sample measurement and analyses were

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

    Energy Technology Data Exchange (ETDEWEB)

    Serrano E, L. A.

    2015-07-01

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

  4. The research on biodistribution of bearing sarcoma mice and rabbit SPECT imaging of 177Lu-DOTMP

    International Nuclear Information System (INIS)

    Deng Xinrong; Xiang Xueqin; Li Fenglin; Fan Caiyun; Liu Zihua; Luo Zhifu; Chen Yang

    2012-01-01

    Cyclen (1, 4, 7, 10-tetraazacyclododecane) and H 3 PO 3 were used to synthesis DOTMP (1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-Tetraaminomethylenephosphonate), and then DOTMP was labelled with 177 Lu. The research of biodistribution of 177 Lu-DOTMP in model mice bearing S180 sarcoma and SPECT imaging in Japanese white rabbit were also carried out. The results of biodistribution of bearing S180 mice indicated that 177 Lu-DOTMP cleared rapidly from blood and was selectively delivered to target bone. The radioactivity uptake was mainly in bone and less in other organs and tissues. The results of SPECT imaging of Japanese white rabbit showed that the radioactivity was accumulated in bladder. 177 Lu-DOTMP was mainly excreted by kidney. The uptake of the activity in the skeleton was observed significantly within 22 h post-injection and it became quite significant at 46 h post-injection. It indicated that 177 Lu-DOTMP has good bone targeting and is worthy of further study. (authors)

  5. Evaluation of cell death mechanisms activated by the administration of the theranostics radiopharmaceutical {sup 177}Lu-DOTA-anti-CD20 in a dose range of 1-5 Gy; Evaluacion de los mecanismos de muerte celular activados por la administracion del radiofarmaco teranostico {sup 177}Lu-DOTA-anti-CD20 en un rango de dosis de 1-5 Gy

    Energy Technology Data Exchange (ETDEWEB)

    Martinez V, B. E.

    2016-07-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2016-10-15

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

  7. Targeted radiotherapy with 177 Lu-DOTA-TATE in athymic mice with induced pancreatic malignant tumours

    International Nuclear Information System (INIS)

    Murphy, M. A de; Pedraza L, M.; Rodriguez C, J.; Ferro F, G.; Murphy S, E.

    2006-01-01

    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 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 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- 177 -DOTA-TATE will act as expected in man, considering kidney radiation. (Author)

  8. 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.

  9. 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.

  10. Radiosynthesis and preclinical studies of 177Lu-labeled sulfadiazine. A possible theranostic agent for deep-seated bacterial infection

    International Nuclear Information System (INIS)

    Syed Ali Raza Naqvi; Rashid Rasheed; Muhammad Tauqeer Ahmed; Ameer Fawad Zahoor

    2017-01-01

    Sulfadiazine acts through inhibition of bacterial dihydropteroate synthetase. The radio-labeling of sulfadiazine with lutetium-177 ( 177 Lu) is expected to serve as a theranostic agent for deep-seated bacterial infections. The radiosynthesis of 177 Lu-sulfadiazine indicated a > 95% yield under optimized reaction conditions, and promising stability was found in blood serum. Biodistribution data in the absence of infection revealed minimal accumulation in key body organs. Kidneys were the main excretory organs, showed an uptake of 1.76 ± 0.09% ID/g organ at 6-h post-injection. Biodistribution, scintigraphic data, glomerular filtration rate, and cytotoxicity results encourage clinical investigation of 177 Lu-sulfadiazine as a novel theranostic agent for deep-seated bacterial infection. (author)

  11. Preparation and in vitro evaluation of 177Lu-iPSMA-RGD as a new heterobivalent radiopharmaceutical

    International Nuclear Information System (INIS)

    Escudero-Castellanos, Alondra; Universidad Autonoma del Estado de Mexico, Toluca, Estado de Mexico; Ocampo-Garcia, B.E.; Ferro-Flores, Guillermina; Santos-Cuevas, C.L.; Isaac-Olive, Keila; Olmos-Ortiz, Andrea; Garcia-Quiroz, Janice; Garcia-Becerra, Rocio; Diaz, Lorenza

    2017-01-01

    This study aimed to synthesize a new 177 Lu-iPSMA-RGD heterobivalent radiopharmaceutical, as well as to assess the in vitro radiopharmaceutical potential to target cancer cells overexpressing PSMA and α(v) β(3) integrins. The radiotracer prepared with a radiochemical purity of 98.8 ± 1.0% showed stability in human serum, specific recognition with suitable affinity to PSMA and α(v)β(3) integrins, and capability to inhibit cancer cell proliferation and VEGF signaling (antiangiogenic effect). Results warrant further preclinical studies to establish the 177 Lu-iPSMA-RGD potential as a dual therapeutic radiopharmaceutical. (author)

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2017-01-15

    . {sup 177}Lu-DKFZ-PSMA-617 radionuclide therapy is a safe and effective approach in the treatment of mCRPC patients. (orig.)

  13. Development of a therapeutic radiopharmaceutical {sup 177}Lu-DOTA- Minigastrin for potential use in PRRT; Desarrollo de un radiofarmaco terapeutico {sup 177}Lu-DOTA-Minigastrina para su potencial uso en PRRT

    Energy Technology Data Exchange (ETDEWEB)

    Lopez Bularte, A. C.; Nevares, N. N.; Zapata, A. M.; Perez, J. H.; Crudo, J. L. [Comision Nacional de Energia Atomica (Argentina); Puerta Yepes, N.; Rojo, A. M. [Autoridad Regulatoria Nuclear (Argentina)

    2010-07-01

    The aim of this work is to obtain {sup 177}Lu-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) {sup 177}LuCl{sub 3} of an intermediate level of Ae (between 6.36 to 17.95 Ci/mg of {sup 176}Lu) ) and also to perform in vitro and in vivo stability tests, dose calculation in normal mice and its extrapolation to a human model. (authors) [Spanish] El objetivo de este trabajo consistio en obtener {sup 177}Lu-DOTA-Minigastrina con una alta pureza radioquimica (PR) y la mayor actividad especifica (Ae) posible, empleando {sup 177}LuCl{sub 3} de media Ae (entre 6,36-17,95 Ci/mg de {sup 176}Lu) de produccion local (Reactor Nuclear RA-3, Centro Atomico Ezeiza), y realizar los ensayos de estabilidad in vitro e in vivo, el calculo de dosis en ratones normales y su extrapolacion a un modelo humano. (autores)

  14. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination with Docetaxel

    National Research Council Canada - National Science Library

    Vallabhajosula, Shankar

    2007-01-01

    Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

  15. Radioimmunotherapy (RIT) Dose-Escalation Studies in Prostate Cancer Using Anti-PSMA Antibody 177Lu-J591: RIT Alone and RIT in Combination With Docetaxel

    National Research Council Canada - National Science Library

    Vallabhajosula, Shankar

    2006-01-01

    Phase I dose escalation studies with 177Lu-DOTA-huJ591 using dose fractionation regimen will be performed in patients with PCa and who have recurrent and/or metastatic disease. The 177Lu dose (20-45 mCi/m2...

  16. Treatment of neuroendocrine tumors (NETs) expressing SMT 90Y and 177Lu

    International Nuclear Information System (INIS)

    Oliva González, Juan P.; Baum, Richard

    2016-01-01

    Neuroendocrine tumors (NETs) are a relatively rare and extremely heterogeneous group, essentially characterized by a different metabolism and endocrine histologically pattern. NETs are a challenge for physicians not only for diagnosis but also for early treatment. In addition to this, QT or RT treatments that require a high rate of cell proliferation to be effective, they are not in these tumors as slow growth. The primary treatment of NETs is surgery, either with a curative intent or tumor shrinkage. Peptide Receptors Radiotherapy (RTPR) consists of the administration for therapeutic purposes of Radiolabeled Synthetic Peptides that bind specifically and with high affinity to receptors of tumor cells. The RTPR of TNE with SMT analogues is effective for handling or metastizados inoperable patients. The Conference gives an accurate picture of the treatment of these tumors both 90 Y as 177 Lu. (author)

  17. Radionuclide study of thyroid function in pediatrics, using sup(99m)Tc, 123I or 131I: 150 case-reports

    International Nuclear Information System (INIS)

    Guillet, J.; Basse-Cathalinat, B.; Soubiran, G.; Blanquet, P.; Guillet, G.

    1981-01-01

    THe best radioisotope for in vivo thyroid investigations is the one which provides the highest quality scintigrams with the least radiation exposure. The choice of 131 I, 123 I or sup(99m)Tc in 150 children is discussed. Cases included 25 dysgenesis, 4 goiters with hypothyroidism, 56 goiters without thyroid dysfunction, 3 thyroiditis, and 11 cold nodules. When thyroid scanning is performed with 131 I, the gland's radiation exposure is high. 123 I is preferable since a fairly high activity can be obtained without delivering an excessive radiation dose. (approximately 2 rad to the thyroid for 50 microCi/m 2 ). sup(99m)Tc which is readily available is not a true iodine analog. It does not give a true picture of iodine metabolism. 123 I was generally used in cases of hypothyroidism, goiter (whenever a defect in thyroid hormone synthesis was suspected) and hyperthyroidism. sup(99m)Tc was generally used in other cases. The low radiation doses delivered by these radioisotopes allows study of thyroid function in the neonate [fr

  18. Radionuclide study of thyroid function in pediatrics, using sup(99m)Tc, /sup 123/I or /sup 131/I: 150 case-reports

    Energy Technology Data Exchange (ETDEWEB)

    Guillet, J.; Basse-Cathalinat, B.; Soubiran, G.; Blanquet, P. (Hopital Pellegrin, 33 - Bordeaux (France)); Guillet, G. (Johns Hopkins Medical Institutions, Baltimore, MD (USA). Div. of Nuclear Medicine)

    1981-11-01

    THe best radioisotope for in vivo thyroid investigations is the one which provides the highest quality scintigrams with the least radiation exposure. The choice of /sup 131/I, /sup 123/I or sup(99m)Tc in 150 children is discussed. Cases included 25 dysgenesis, 4 goiters with hypothyroidism, 56 goiters without thyroid dysfunction, 3 thyroiditis, and 11 cold nodules. When thyroid scanning is performed with /sup 131/I, the gland's radiation exposure is high. /sup 123/I is preferable since a fairly high activity can be obtained without delivering an excessive radiation dose. (approximately 2 rad to the thyroid for 50 microCi/m/sup 2/). sup(99m)Tc which is readily available is not a true iodine analog. It does not give a true picture of iodine metabolism. /sup 123/I was generally used in cases of hypothyroidism, goiter (whenever a defect in thyroid hormone synthesis was suspected) and hyperthyroidism. sup(99m)Tc was generally used in other cases. The low radiation doses delivered by these radioisotopes allows study of thyroid function in the neonate.

  19. 177Lu-DTPA-BIS-BIOTIN Binding of Octreotide-dextran-avidinated PANC-1 Cell Lines in Vitro

    International Nuclear Information System (INIS)

    Deng Xinrong; Zhai Shizhen; Shen Yijia; Luo Zhifu; Du Jin

    2011-01-01

    Tyr3-octreotide, dextran-40 and avidin were used to prepare octreotide-dextran-avidin (TOC-Dx 40 -Av). DTPA-BIS-BIOTIN was labelled with 177 Lu. The in vitro somatostatin receptor binding study was carried out by pretargeted method using TOC-Dx 40 -Av and 177 Lu-DTPA-BIS-BIOTIN. The 24 well cell culture plates were prepared with PANC-1 cell monolayer and then incubated with TOC-Dx 40 -Av. After two washed with PBS, the cells were incubated with different concentration of 177 Lu-DTPA-BIS-BIOTIN (48.8 ∼ 391 pmol). Cells uptake was evaluated with γ counter. The results showed that the chemical purity of TOC-Dx 40 -Av was over 99%. The results also showed that TOC-Dx 40 -Av remained high receptor binding affinity to somatostatin receptor which indicated that TOC- Dx 40 -Av could bind to 177 Lu-DTPA-BIS-BIOTIN with the molar ratio of 1 : 1 on the cell surface. (authors)

  20. Preclinical Evaluation of (177)Lu-Nimotuzumab: A Potential Tool for Radioimmunotherapy of Epidermal Growth Factor Receptor-Overexpressing Tumors

    Czech Academy of Sciences Publication Activity Database

    Beckford, Denis R.; Eigner, Sebastian; Beran, Miloš; Eigner-Henke, Kateřina; Lázníček, M.; Melichar, František; Chinol, M.

    2011-01-01

    Roč. 26, č. 3 (2011), s. 287-297 ISSN 1084-9785 R&D Projects: GA MŠk OE08018 Institutional research plan: CEZ:AV0Z10480505 Keywords : EGFR * (177)Lu * monoclonal antibodies * Nimotuzumab Subject RIV: FR - Pharmacology ; Medidal Chemistry Impact factor: 1.787, year: 2011

  1. Doses rate in contact with plastic syringes of 1, 2 and 5 mL for different beta and gamma emitting radionuclides

    International Nuclear Information System (INIS)

    Torres Berdeguez, Mirta; Ayra Pardo, Enrique; Falcon, Lazaro

    2008-01-01

    The objective of this paper is to calculate the dose rate in contact with plastic syringes of 1, 2 and 5 m L volume, unshielded and the dose rate in the same syringes after a lead or a Lucite shield of various thickness has been installed, depending on the emission of the radionuclide used. The radionuclides involved in the assessment were 32 P, 51 Cr, 90 Y, 99m Tc, 125 I, 131 I, 153 Sm, 186 Re, 188 Re, 169 Er and 177 Lu. The code used was the MCNP4C. The results are intended to be used by a Radiation Protection Officer wherever the radionuclides in question are handled to rapidly assess the dose in hands of the operators. (author)

  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. An assessment tumor targeting ability of 177Lu labeled cyclic CCK analogue peptide by binding with cholecystokinin receptor

    Directory of Open Access Journals (Sweden)

    Eun-Ha Cho

    2016-07-01

    Full Text Available The cholecystokinin (CCK receptor is known as a receptor that is overexpressed in many human tumors. The present study was designed to investigate the targeting ability of cyclic CCK analogue in AR42J pancreatic cells. The CCK analogues, DOTA-K(glucose-Gly-Trp-Nle-Asp-Phe (DOTA-glucose-CCK and DOTA-Nle-cyclo(Glu-Trp-Nle-Asp-Phe-Lys-NH2 (DOTA-[Nle]-cCCK, were synthesized and radiolabeled with 177Lu, and competitive binding was evaluated. The binding appearance of synthesized peptide with AR42J cells was evaluated by confocal microscopy. And bio-distribution was performed in AR42J xenografted mice. Synthesized peptides were prepared by a solid phase synthesis method, and their purity was over 98%. DOTA is the chelating agent for 177Lu-labeling, in which the peptides were radiolabeled with 177Lu by a high radiolabeling yield. A competitive displacement of 125I-CCK8 on the AR42J cells revealed that the 50% inhibitory concentration value (IC50 was 12.3 nM of DOTA-glucose-CCK and 1.7 nM of DOTA-[Nle]-cCCK. Radio-labeled peptides were accumulated in AR42J tumor in vivo, and %ID/g of the tumor was 0.4 and 0.9 at 2 h p.i. It was concluded that 177Lu-DOTA-[Nle]-cCCK has higher binding affinity than 177Lu-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors.

  4. The in vivo disposition and in vitro transmembrane transport of two model radiometabolites of DOTA-conjugated receptor-specific peptides labelled with (177) Lu.

    Science.gov (United States)

    Volková, Marie; Mandíková, Jana; Bárta, Pavel; Navrátilová, Lucie; Lázníčková, Alice; Trejtnar, František

    2015-01-01

    In vivo metabolism of the radiolabelled receptor-specific peptides has been described; however, information regarding the pharmacokinetic behaviour of the degradation products within the body is very scarce. The present study was designed to obtain new knowledge on the disposition and elimination of low-molecular radiometabolites of receptor-specific peptides in the organism and to reveal the potential involvement of selected membrane transport mechanisms in the cellular uptake of radiometabolites, especially in the kidney. The study compared pharmacokinetics of two radiometabolites: a final metabolite of somatostatin analogues, (177)Lu-DOTA-DPhe, and a tripeptide metabolite of (177)Lu-DOTA-minigastrin 11, (177)Lu-DOTA-DGlu-Ala-Tyr. Their pharmacokinetics was compared with that of respective parent (177)Lu-radiopeptide. Both radiometabolites exhibited relative rapid clearing from most body tissues in rats in vivo along with predominant renal excretion. The long-term renal retention of the smaller radiometabolite (177)Lu-DOTA-DPhe was lower than that of (177)Lu-DOTA-DGlu-Ala-Tyr. An uptake of (177)Lu-DOTA-DPhe by human renal influx transporter organic cation transporter 2 was found in vitro in a cellular model. The study brings the first experimental data on the in vivo pharmacokinetics of radiometabolites of receptor-specific somatostatin and gastrin analogues. The found results may indicate a negative correlation between the degree of decomposition of the parent peptide chain and the renal retention of the metabolite. Copyright © 2015 John Wiley & Sons, Ltd.

  5. In vivo biological evaluation of 131I radiolabeled-paclitaxel glucuronide (131I-PAC-G)

    International Nuclear Information System (INIS)

    Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P.

    2012-01-01

    Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high β-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with 131 I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with 131 I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of 131 I-PAC-G was 84.30 ± 7.40% (n=10). The biodistribution of 131 I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that 131 I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that 131 I-PAC-G bears a therapy potential because of the 131 I radionuclide and can be improved with further investigations. (orig.)

  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. Third-line treatment and 177Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

    International Nuclear Information System (INIS)

    Edler von Eyben, Finn; Roviello, Giandomenico; Kiljunen, Timo; Kairemo, Kalevi; Joensuu, Timo; Uprimny, Christian; Virgolini, Irene

    2018-01-01

    There is a controversy as to the relative efficacy of 177 Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether 177 Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Twelve studies including 669 patients reported 177 Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with 177 Lu-PSMA RLT. The treatment with 177 Lu-PSMA-617 and 177 Lu-PSMA for imaging and therapy (I and T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. 177 Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). 177 Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ 2 test). Median survival was longer after 177 Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for 177 Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ 2 test). As for patients with mCRPC, treatment with 177 Lu

  8. Third-line treatment and {sup 177}Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Edler von Eyben, Finn [Center of Tobacco Control Research, Odense (Denmark); Roviello, Giandomenico [San Donato Hospital, Department of Oncology, Medical Oncology Unit, Arezzo (Italy); University of Trieste, Department Medical, Surgery, and Health Sciences, Trieste (Italy); Kiljunen, Timo; Kairemo, Kalevi; Joensuu, Timo [Docrates Cancer Center, Helsinki (Finland); Uprimny, Christian; Virgolini, Irene [University Hospital Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria)

    2018-03-15

    There is a controversy as to the relative efficacy of {sup 177}Lu prostate specific membrane antigen (PSMA) radioligand therapy (RLT) and third-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC). The aim of our systematic review was to elucidate whether {sup 177}Lu-PSMA RLT and third-line treatment have similar effects and adverse effects (PROSPERO ID CRD42017067743). The review followed Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Searches in Pubmed and Embase selected articles up to September 2017. A search in ClinicalTrials.gov indicated ongoing studies. The meta-analysis used the random-effects model. Twelve studies including 669 patients reported {sup 177}Lu-PSMA RLT. Overall, 43% of the patients had a maximum decline of PSA of ≥50% following treatment with {sup 177}Lu-PSMA RLT. The treatment with {sup 177}Lu-PSMA-617 and {sup 177}Lu-PSMA for imaging and therapy (I and T) had mainly transient adverse effects. Sixteen studies including 1338 patients reported third-line treatment. Overall, 21% of the patients had a best decline of PSA of ≥50% following third-line treatment. After third-line treatment with enzalutamide and cabazitaxel, adverse effects caused discontinuation of treatment for 10% to 23% of the patients. {sup 177}Lu-PSMA RLT gave a best PSA decline ≥50% more often than third-line treatment (mean 44% versus 22%, p = 0.0002, t test). {sup 177}Lu-PSMA RLT gave objective remission more often than third-line treatment (overall 31 of 109 patients versus 43 of 275 patients, p = 0.004, χ{sup 2} test). Median survival was longer after {sup 177}Lu-PSMA RLT than after third-line treatment, but the difference was not statistically significant (mean 14 months versus 12 months, p = 0.32, t test). Adverse effects caused discontinuation of treatment more often for third-line treatment than for {sup 177}Lu-PSMA RLT (22 of 66 patients versus 0 of 469 patients, p < 0.001, χ{sup 2

  9. Synthesis and in vitro evaluation of an antiangiogenic cancer-specific dual-targeting 177Lu-Au-nanoradiopharmaceutical

    International Nuclear Information System (INIS)

    Gonzalez-Ruiz, Abraham; Ferro-Flores, Guillermina; Azorin-Vega, Erika; Ocampo-Garcia, Blanca; Maria Ramirez, Flor de; Santos-Cuevas, Clara; Luna-Gutierrez, Myrna; Leon-Rodriguez, Luis De; Isaac-Olive, Keila; Morales-Avila, Enrique

    2017-01-01

    The aim of this research was to synthesize and chemically characterize a cancer-specific 177 Lu-Au-nanoradiopharmaceutical based on gold nanoparticles (NPs), the nuclear localization sequence (NLS)-Arg-Gly-Asp peptide and an aptamer (HS-pentyl-pegaptanib) to target both the α(v)β(3) integrin and the vascular endothelial growth factor (VEGF) overexpressed in the tumor neovasculature, as well as to evaluate by the tube formation assay, the nanosystem capability to inhibit angiogenesis. 177 Lu-NP-RGD-NLS-Aptamer was obtained with a radiochemical purity of 99 ± 1%. Complete inhibition of tube formation (angiogenesis) was demonstrated when endothelial cells (EA.hy926), cultured in a 3D-extracellular matrix support, were treated with the developed nanosystem. (author)

  10. Therapeutic Efficacy with Treatment-related Toxicities of 177Lu-labeled Bombesin Derivative for the Peptide Receptor Radiotherapy

    International Nuclear Information System (INIS)

    Lim, Jae Cheong; Cho, Eun Ha; Lee, So Young

    2015-01-01

    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 177 Lu-labeled bombesin derivative has promising characteristics as a novel nuclear medicine, especially for the treatment of GRPR over-expressing prostate tumors

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

    Directory of Open Access Journals (Sweden)

    Héctor Mendoza-Nava

    2016-01-01

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

  12. [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

    Science.gov (United States)

    Baum, Richard P.; Kluge, Andreas W.; Kulkarni, Harshad; Schorr-Neufing, Ulrike; Niepsch, Karin; Bitterlich, Norman; van Echteld, Cees J.A.

    2016-01-01

    Purpose: To characterise efficacy and safety of 177Lu-DOTATOC as agent for peptide receptor radiotherapy (PRRT) of advanced neuroendocrine tumours (NET). Patients and methods: Fifty-six subjects with metastasized and progressive NET (50% gastroenteral, 26.8% pancreatic, 23.2% other primary sites) treated consecutively with 177Lu-DOTATOC were analysed retrospectively. Subjects were administered 177Lu-DOTATOC (mean 2.1 cycles; range 1-4) as 7.0GBq (median) doses at three-monthly intervals. Efficacy was analysed using CT and/or MRI according to RECIST 1.1 criteria and results were stratified for the number of administered cycles and the primary tumour origin. Results: In the total NET population (A), median progression-free (PFS) and overall survival (OS) were 17.4 and 34.2 months, respectively, assessed in a follow-up time (mean ± SD) of 16.1 ± 12.4 months. In patients receiving more than one cycle, mean follow-up time was 22.4 ± 11.0 months for all NETs (B) and PFS was 32.0 months for all NETs (B), 34.5 months for GEP-NET (C), and 11.9 months for other NETs (D). Objective response rates (Complete/Partial Responses) were 33.9%, 40.6%, 54.2%, and 0% for A, B, C, and D groups, respectively, while disease control rates in the same were 66.1%, 93.8%, 100%, and 75%. Complete responses (16.1%, 18.8% and 25.0% for groups A, B and C) were high, 78% of which were maintained throughout the follow up. There were no serious adverse events. One case of self-limiting grade 3 myelotoxicity was reported. Although 20% of patients had mild renal insufficiency at baseline, there was no evidence of exacerbated or de novo renal toxicity after treatment. Conclusion: 177Lu-DOTATOC is a novel agent for PRRT with major potential to induce objective tumour responses and sustained disease control in progressive neuroendocrine tumours, even when administered in moderate activities. The observed safety profile suggests a particularly favourable therapeutic index, including in patients with

  13. 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)

  14. 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.

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

    International Nuclear Information System (INIS)

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

    2015-01-01

    those with more advanced changes (Steinbrocker's Grades III and IV) in terms of VAS improvement (75% vs. 45.8%) (P < 0.001). The overall success rate (VAS ≥ 50) was 80%. Remission of pain during the night was achieved in 100%, and knee flexibility was improved in 80%. The changes in the blood pool phase before RSV were 3.2 ± 0.7 and after the therapy 1.4 ± 0.7 (P < 0.001). The J/B ratio was: Before RSV 2.4 ± 0.3; after treatment 1.0 ± 0.2 (P < 0.05). CRP concentration 4 and 24 weeks after the therapy was significantly lower than before treatment. The fibrinogen level was not different before and after RSV. RSV side-effects assessed for the whole follow-up period were minor and not significant. RSV with 177 Lu-HA was safe and effective in patients with knee joint chronic painful synovitis of rheumatoid origin. It exhibited significant therapeutic effect after 6 months follow-up period with no significant side-effects. The preliminary investigations reveal that 177 Lu-labeled HA particles hold considerable promise as a cost-effective agent for RSV. More elaborate and controlled clinical trials are necessary to evaluate the therapeutic efficacy and safety of the agent compared with the treatment with other radionuclides and glucocorticosteroids

  16. Encapsulation of a radiolabeled cluster inside a fullerene cage, (177)Lu(x)Lu((3-x))N@C(80): an interleukin-13-conjugated radiolabeled metallofullerene platform.

    Science.gov (United States)

    Shultz, Michael D; Duchamp, James C; Wilson, John D; Shu, Chun-Ying; Ge, Jiechao; Zhang, Jianyuan; Gibson, Harry W; Fillmore, Helen L; Hirsch, Jerry I; Dorn, Harry C; Fatouros, Panos P

    2010-04-14

    In this communication, we describe the successful encapsulation of (177)Lu into the endohedral metallofullerene (177)Lu(x)Lu(3-x)N@C(80) (x = 1-3) starting with (177)LuCl(3) in a modified quartz Kraschmer-Huffman electric generator. We demonstrate that the (177)Lu (beta-emitter) in this fullerene cage is not significantly released for a period of up to at least one-half-life (6.7 days). We also demonstrate that this agent can be conjugated with an interleukin-13 peptide that is designed to target an overexpressed receptor in glioblastoma multiforme tumors. This nanoparticle delivery platform provides flexibility for a wide range of radiotherapeutic and radiodiagnostic multimodal applications.

  17. 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)

    Vilchis J, A.

    2013-01-01

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

  18. Evaluation of cell death mechanisms activated by the administration of the theranostics radiopharmaceutical "1"7"7Lu-DOTA-anti-CD20 in a dose range of 1-5 Gy

    International Nuclear Information System (INIS)

    Martinez V, B. E.

    2016-01-01

    Radio-immunotherapy with anti-CD20 antibodies significantly increases the rate of remission in patients with CD20 over expressing B-cell lymphomas. Radio-labeled antibodies directed to surface antigens allow delivering scaled doses of radiation to specific targets thus limiting the dose to healthy tissue. Anti-CD20 causes cell death by two major pathways; activating the immune system to destroy malignant cells and inducing the activation of cell death pathways. The "1"7"7Lu is a beta particle emitter (max. 0.497 MeV) with a maximum soft tissue reach of 0.7 mm and a half-life of 6.7 days. Several clinical studies have established a maximum tolerated dose (45m Ci/m"2) for "1"7"7Lu-DOTA-rituximab, which shows a favorable clinical response without hematological toxicity. However, the molecular mechanisms of synergistic activation of anti-CD20 and radionuclide have not been studied. In this work we evaluated by flow cytometry, the activation kinetics of the cell death mechanisms induced by the treatment with "1"7"7Lu-DOTA-anti-CD20 from non-Hod king lymphoma cells (Raji). The absorbed radiation dose delivered to the cell nucleus was calculated by Monte Carlo simulation, considering the contribution of the beta emissions of the radiopharmaceutical present in the cell membrane and surrounding environment, as well as crossfire. This work shows that the application of radiation doses of 1 to 5 Gy of the radiopharmaceutical "1"7"7Lu-DOTA-anti-CD20 are sufficient to induce cell death by apoptosis and arrest of the cell cycle. The combination of these factors (continuous delivery of radiation activation of repair mechanisms and increased radio-sensitivity) causes acute activation of the apoptotic program resulting in significant cell death after 96 h of treatment. The temporal analysis of cell death suggests the early activation of apoptosis that is counteracted by the activation of repair processes caused by sustained irradiation, which leads to cell arrest and increases

  19. 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

  20. 177Lu-immunotherapy of experimental peritoneal carcinomatosis shows comparable effectiveness to 213Bi-immunotherapy, but causes toxicity not observed with 213Bi

    International Nuclear Information System (INIS)

    Seidl, Christof; Zoeckler, Christine; Beck, Roswitha; Senekowitsch-Schmidtke, Reingard; Quintanilla-Martinez, Leticia; Bruchertseifer, Frank

    2011-01-01

    213 Bi-d9MAb-immunoconjugates targeting gastric cancer cells have effectively cured peritoneal carcinomatosis in a nude mouse model following intraperitoneal injection. Because the β-emitter 177 Lu has proven to be beneficial in targeted therapy, 177 Lu-d9MAb was investigated in this study in order to compare its therapeutic efficacy and toxicity with those of 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 177 Lu-d9MAb immunoconjugates targeting d9-E-cadherin or with nonspecific 177 Lu-d8MAb. Therapeutic efficacy was evaluated by monitoring survival for up to 250 days. For evaluation of toxicity, both biodistribution of 177 Lu-d9MAb and blood cell counts were determined at different time points and organs were examined histopathologically. Treatment with 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 177 Lu-d9MAb conjugates were superior to nonspecific 177 Lu-d8MAb. Treatment with 7.4 MBq of 177 Lu-d9MAb was most successful, with 90% of the animals surviving longer than 250 days. However, treatment with therapeutically effective activities of 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 213 Bi-d9MAb at comparable therapeutic efficacy. The therapeutic efficacy of 177 Lu-d9MAb conjugates in peritoneal carcinomatosis is impaired by toxic side effects. Because previous therapy with 213 Bi-d9MAb revealed comparable therapeutic efficacy without toxicity it should be preferred for the treatment of peritoneal carcinomatosis. (orig.)

  1. Safety, Pharmacokinetics and Dosimetry of a Long-Acting Radiolabeled Somatostatin Analogue 177Lu-DOTA-EB-TATE in Patients with Advanced Metastatic Neuroendocrine Tumors.

    Science.gov (United States)

    Zhang, Jingjing; Wang, Hao; Jacobson Weiss, Orit; Cheng, Yuejuan; Niu, Gang; Li, Fang; Bai, Chunmei; Zhu, Zhaohui; Chen, Xiaoyuan

    2018-04-13

    Radiolabeled somatostatin analogue therapy has become an established treatment method for patients with well to moderately differentiated unresectable or metastatic neuroendocrine tumors (NETs). The most frequently used somatostatin analogues in clinical practice are octreotide and octreotate. However, both peptides showed suboptimal retention within tumors. The aim of this first-in-human study is to explore the safety and dosimetry of a long-acting radiolabeled somatostatin analogue, lutetium-177-1, 4, 7, 10-tetra-azacyclododecane-1, 4, 7, 10-tetraacetic acid-Evans blue-octreotate ( 177 Lu-DOTA-EB-TATE). Methods: Eight patients (6 males and 2 females; age range, 27-61 y) with advanced metastatic neuroendocrine tumors were recruited. Five patients received a single dose 0.35-0.70 GBq (9.5-18.9 mCi) of 177 Lu-DOTA-EB-TATE and underwent serial whole body planar and single-photon emission computed tomography-computed tomography (SPECT-CT) scans at 2, 24, 72, 120 and 168 h after injection. The other 3 patients received intravenous injection of 0.28-0.41 GBq (7.5-11.1 mCi) of 177 Lu-DOTATATE for the same imaging acquisition procedures at 1, 3, 4, 24 and 72 h after injection. The dosimetry was calculated using the OLINDA/EXM 1.1 software. Results: Administration of 177 Lu-DOTA-EB-TATE was well tolerated, with no adverse symptoms being noticed or reported in any of the patients. Compared with 177 Lu-DOTATATE, 177 Lu-DOTA-EB-TATE showed extended circulation in the blood and achieved 7.9-fold increase of tumor dose delivery. The total body effective doses were 0.205 ± 0.161 mSv/MBq for 177 Lu-DOTA-EB-TATE and 0.174 ± 0.072 mSv/MBq for 177 Lu-DOTATATE. Significant dose delivery increases to the kidneys and bone marrow were also observed in patients receiving 177 Lu-DOTA-EB-TATE than those receiving 177 Lu-DOTATATE (3.2 and 18.2-fold, respectively). Conclusion: By introducing an albumin binding moiety, 177 Lu-DOTA-EB-TATE showed remarkably higher uptake and retention in NET

  2. Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer 177Lu-AMBA

    International Nuclear Information System (INIS)

    Waser, Beatrice; Eltschinger, Veronique; Reubi, Jean C.; Linder, Karen; Nunn, Adrian

    2007-01-01

    To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, 177 Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand 177 Lu-AMBA was used and compared with established bombesin radioligands such as 125 I-Tyr 4 -bombesin and 125 I-[D-Tyr 6 ,β-Ala 11 ,Phe 13 ,Nle 14 ]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. 177 Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. 177 Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with 177 Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with 177 Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with 177 Lu-AMBA than with the conventional bombesin radioligands. The present in vitro study suggests that 177 Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels. (orig.)

  3. Selective in vitro targeting of GRP and NMB receptors in human tumours with the new bombesin tracer {sup 177}Lu-AMBA

    Energy Technology Data Exchange (ETDEWEB)

    Waser, Beatrice; Eltschinger, Veronique; Reubi, Jean C. [University of Berne, Division of Cell Biology and Experimental Cancer Research, Institute of Pathology, P.O. Box 62, Bern (Switzerland); Linder, Karen; Nunn, Adrian [Bracco Research USA Inc, Princeton, NJ (United States)

    2007-01-15

    To investigate the in vitro binding properties of a novel radiolabelled bombesin analogue, {sup 177}Lu-AMBA, in human neoplastic and non-neoplastic tissues selected for their expression of the bombesin receptor subtypes GRP-R, NMB-R and BRS-3. In vitro receptor autoradiography was performed in cancers expressing the various bombesin receptor subtypes. The novel radioligand {sup 177}Lu-AMBA was used and compared with established bombesin radioligands such as {sup 125}I-Tyr{sup 4}-bombesin and {sup 125}I-[D-Tyr{sup 6},{beta}-Ala{sup 11},Phe{sup 13},Nle{sup 14}]-bombesin(6-14). In vitro incidence of detection of each of the three bombesin receptor subtypes was evaluated in each tumour. {sup 177}Lu-AMBA identified all GRP-R-expressing tumours, such as prostatic, mammary and renal cell carcinomas as well as gastrointestinal stromal tumours. {sup 177}Lu-AMBA also identified all NMB-expressing tumours, but did not detect BRS-3-expressing tumours or BRS-3-expressing pancreatic islets. GRP-R-expressing peritumoural vessels were heavily labelled with {sup 177}Lu-AMBA. In contrast to the strongly GRP-R-positive mouse pancreas, the human pancreas was not labelled with {sup 177}Lu-AMBA unless chronic pancreatitis was diagnosed. In general, the sensitivity was slightly better with {sup 177}Lu-AMBA than with the conventional bombesin radioligands. The present in vitro study suggests that {sup 177}Lu-AMBA may be a very useful in vivo targeting agent for GRP-R-expressing tumours, NMB-R-expressing tumours and GRP-R-expressing neoangiogenic vessels. (orig.)

  4. {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.)

  5. 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

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

    International Nuclear Information System (INIS)

    Makis, William; Mccann, Karey; Mcewan, Alexander J. B.

    2015-01-01

    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 177 Lu-[DOTA0,Tyr3]octreotate (DOTATATE) radioisotope therapy using established protocols. Three paraganglioma patients were treated with 4–5 cycles of 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 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 177 Lu-DOTATATE. Subsequent 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. 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

  7. 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.

  8. Individualised {sup 177}Lu-DOTATATE treatment of neuroendocrine tumours based on kidney dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Sundloev, Anna; Tennvall, Jan [Lund University, Department of Oncology and Pathology, Clinical Sciences, Lund (Sweden); Skaane University Hospital, Department of Oncology, Lund (Sweden); Sjoegreen-Gleisner, Katarina; Ljungberg, Michael [Lund University, Department of Medical Radiation Physics, Clinical Sciences, Lund (Sweden); Svensson, Johanna [Sahlgrenska University Hospital, Department of Oncology, Gothenburg (Sweden); Olsson, Tomas [Skaane University Hospital, Department of Oncology, Lund (Sweden); Bernhardt, Peter [University of Gothenburg, Department of Radiation Physics, Gothenburg (Sweden); Sahlgrenska University Hospital, Department of Medical Physics and Biomedical Engineering, Gothenburg (Sweden)

    2017-08-15

    To present data from an interim analysis of a Phase II trial designed to determine the feasibility, safety, and efficacy of individualising treatment based on renal dosimetry, by giving as many cycles as possible within a maximum renal biologically effective dose (BED). Treatment was given with repeated cycles of 7.4 GBq {sup 177}Lu-DOTATATE at 8-12-week intervals. Detailed dosimetry was performed in all patients after each cycle using a hybrid method (SPECT + planar imaging). All patients received treatment up to a renal BED of 27 ± 2 Gy (α/β = 2.6 Gy) (Step 1). Selected patients were offered further treatment up to a renal BED of 40 ± 2 Gy (Step 2). Renal function was followed by estimation and measurement of the glomerular filtration rate (GFR). Fifty-one patients were included in the present analysis. Among the patients who received treatment as planned, the median number of cycles in Step 1 was 5 (range 3-7), and for those who completed Step 2 it was 7 (range 5-8); 73% were able to receive >4 cycles. Although GFR decreased in most patients after the completion of treatment, no grade 3-4 toxicity was observed. Patients with a reduced baseline GFR seemed to have an increased risk of GFR decline. Five patients received treatment in Step 2, none of whom exhibited a significant reduction in renal function. Individualising PRRT using renal dosimetry seems feasible and safe and leads to an increased number of cycles in the majority of patients. The trial will continue as planned. (orig.)

  9. Indirect and direct measurement of thermal neutron acceleration by inelastic scattering on the 177Lu isomer

    International Nuclear Information System (INIS)

    Belier, G.; Roig, O.; Meot, V.; Daugas, J.M.; Aupiais, J.; Jutier, Ch.; Le Petit, G.; Veyssiere, Ch.

    2008-01-01

    When neutrons interact with isomers, these isomers can de-excite and in such a reaction the outgoing neutron has an energy greater than the in-going one. This process is referred as Inelastic Neutron Acceleration or Super-elastic Scattering. Up to now this process was observed for only two nucleus, 152m Eu and 180m Hf by measuring the number of fast neutrons produced by isomeric targets irradiated with thermal neutrons. In these experiments the energies of the accelerated neutrons were not measured. This report presents an indirect measurement of inelastic neutron acceleration on 177m Lu, based on the burn-up and the radiative capture cross sections measurements. Since at thermal energies the inelastic scattering and the radiative capture are the only processes that contribute to the isomer burn-up, the inelastic cross section can be deduced from the difference between the two measured quantities. Applying this method for the 177 Lu isomer with different neutron fluxes we obtained a value of (257 ± 50) barns (for a temperature of 323 K) and determined that there is no integral resonance for this process. In addition the radiative capture cross section on 177g Lu was measured with a much better accuracy than the accepted value. Since the acceleration cross section is quite high, a direct measurement of this process was undertaken, sending thermal neutrons and measuring the fast neutrons. The main goal now is to measure the outgoing neutron energies in order to identify the neutron transitions in the exit channel. In particular the K conservation question can be addressed by such a measurement. (author)

  10. Radionuclidic contamination of 99Mo, 131I and 103Ru in the eluate of 99Mo-99mTc chromatographic generator: comparision on fission produced 99Mo from RPC, Nordio and ARI

    International Nuclear Information System (INIS)

    Soenarjo, Sunarhadijoso; Gunawan, Adang Hardi

    1996-01-01

    The 99 Mo- 99m Tc Chromatographic generators is the most popular system to provide 99m Tc medical radioisotope. Radioisotope Production Centre (RPC)- BATAN has routinely produced the generator loaded with 99 Mo prepared by 235 U fission. By using fission produced 99 Mo, the resulting 99m Tc is potentially contaminated by other fission products which are difficult to eliminate completely. In order to study the characteristic of the generator and radionuclidic impurity pattern of the 99m Tc eluates, an evaluation of gamma spectrometric determination has been carried out. The bulk solutions of 99 Mo produced by RPC BATAN (Indonesia), Nordion (Canada) and ARI (Australia) were loaded to generators manufactured between July 1993 to May 1994. The saline-eluate 99m Tc, in a total volume of 10 ml each, was subjected to gamma spectrometric determination. The radiation of 99m Tc was eliminated by lead shield of 0.6913 cm thickness. The 99m Tc yield fluctuation from 28 generators indicated that the characteristics of the generator columns were very good. The 99m Tc eluates were consistently contaminated by 99 Mo, 131 I and 103 Ru, although the contamination level in all cases did not exceed the maximum permissible levels. The fluctuation of radionuclidic impurities were probably caused by variation in the irradiation parameter or by variation in the 99 Mo separation methods. (author), 23 refs, 1 tab, 3 figs

  11. 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)

  12. Favorable Response of Metastatic Merkel Cell Carcinoma to Targeted 177Lu-DOTATATE Therapy: Will PRRT Evolve to Become an Important Approach in Receptor-Positive Cases?

    Science.gov (United States)

    Basu, Sandip; Ranade, Rohit

    2016-06-01

    This report illustrates an excellent partial response of Merkel cell carcinoma with multiple bilobar hepatic metastases to a single cycle of peptide receptor radionuclide therapy (PRRT) with (177)Lu-DOTATATE. This response, coupled with minimal side effects, warrants consideration of this therapy early in the disease course (rather than at an advanced stage after failure of other therapies) if the metastatic lesions exhibit adequate tracer avidity on somatostatin receptor-based imaging. Our patient showed progression of systemic disease after having undergone a second surgery and adjuvant radiotherapy to the head and neck, as well as chemotherapy, and hence was considered a candidate for PRRT. In a pretreatment study, the metastatic lesions demonstrated avidity to both somatostatin receptors and (18)F-FDG. Three months after the first cycle of treatment, when the patient was being evaluated for a second cycle, both imaging parameters showed evidence of a partial response that included nearly complete resolution of the two previously seen lesions. In view of the relatively good tolerability, minimal side effects, and targeted nature of the treatment, PRRT may evolve to become the first-line therapy for metastatic Merkel cell carcinoma and should be examined further in a larger number of patients. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  13. 68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology.

    Science.gov (United States)

    Dalm, Simone U; Bakker, Ingrid L; de Blois, Erik; Doeswijk, Gabriela N; Konijnenberg, Mark W; Orlandi, Francesca; Barbato, Donato; Tedesco, Mattia; Maina, Theodosia; Nock, Berthold A; de Jong, Marion

    2017-02-01

    Because overexpression of the gastrin-releasing peptide receptor (GRPR) has been reported on various cancer types, for example, prostate cancer and breast cancer, targeting this receptor with radioligands might have a significant impact on staging and treatment of GRPR-expressing tumors. NeoBOMB1 is a novel DOTA-coupled GRPR antagonist with high affinity for GRPR and excellent in vivo stability. The purpose of this preclinical study was to further explore the use of NeoBOMB1 for theranostic application by determining the biodistribution of 68 Ga-NeoBOMB1 and 177 Lu-NeoBOMB1. PC-3 tumor-xenografted BALB/c nu/nu mice were injected with either approximately 13 MBq/250 pmol 68 Ga-NeoBOMB1 or a low (∼1 MBq/200 pmol) versus high (∼1 MBq/10 pmol) peptide amount of 177 Lu-NeoBOMB1, after which biodistribution and imaging studies were performed. At 6 time points (15, 30, 60, 120, 240, and 360 min for 68 Ga-NeoBOMB1 and 1, 4, 24, 48, 96, and 168 h for 177 Lu-NeoBOMB1) postinjection tumor and organ uptake was determined. To assess receptor specificity, additional groups of animals were coinjected with an excess of unlabeled NeoBOMB1. Results of the biodistribution studies were used to determine pharmacokinetics and dosimetry. Furthermore, PET/CT and SPECT/MRI were performed. Injection of approximately 250 pmol 68 Ga-NeoBOMB1 resulted in a tumor and pancreas uptake of 12.4 ± 2.3 and 22.7 ± 3.3 percentage injected dose per gram (%ID/g) of tissue, respectively, at 120 min after injection. 177 Lu-NeoBOMB1 biodistribution studies revealed a higher tumor uptake (17.9 ± 3.3 vs. 11.6 ± 1.3 %ID/g of tissue at 240 min after injection) and a lower pancreatic uptake (19.8 ± 6.9 vs. 105 ± 13 %ID/g of tissue at 240 min after injection) with the higher peptide amount injected, leading to a significant increase in the absorbed dose to the tumor versus the pancreas (200 pmol, 570 vs. 265 mGy/MBq; 10 pmol, 435 vs. 1393 mGy/MBq). Using these data to predict patient dosimetry, we found

  14. 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.)

  15. 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)

  16. Application of single-vial ready-for-use formulation of 111In- or 177Lu-labelled somatostatin analogs.

    Science.gov (United States)

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

    2014-02-01

    For the sake of safety it would be desirable to store and transport the ready-for-use liquid formulation (diagnostics and therapeutics) of radiolabelled peptides. The use of ethanol, in combination with a mixture of gentisic- and ascorbic acid, has superior effects on stabilizing radiolabelled somatostatin analogs. As a consequence, (111)In- and (177)Lu-labelled somatostatin analogs can be stored and transported in a single-vial ready-for-use liquid formulation up to 7 days after radiolabelling. © 2013 Published by Elsevier Ltd.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-07-01

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

  18. Synthesis of (131)I-labeled-[(131)I]iodo-17-allylamino-17-demethoxy geldanamycin ([(131)I]iodo-17-AAG) and its biodistribution in mice.

    Science.gov (United States)

    Daozhen, Chen; Lu, Liu; Min, Yang; Xinyu, Jiang; Ying, Huang

    2007-10-01

    The aim of this study was to examine the radioiodinating condition of 17-allylamino-17-demethoxy geldanamycin (17-AAG) and observe its biodistribution in the hepatoma cell line HepA tumorearing ICR mice for understanding the possibility of its application in nuclear medicine. [(131)I]iodo-17-AAG was prepared by the reaction of 17-AAG with Na[(131)I] in the presence of hydrogen peroxide. [(131)I]iodo-17-AAG was purified by high-performance liquid chromatography (HPLC). The stability of [(131)I]iodo-17-AAG was measured by thin-layer chromatography (TLC). The distributions in HepA tumor-bearing ICR mice at 0.5, 1, 4, 8, 24, and 48 hours after injection of [(131)I]iodo-17-AAG were measured. Tumor uptake studies were performed in HepA tumor-bearing ICR mice. The labeling yield was over 83%. The radiochemical purity of [(131)I]iodo-17-AAG was 99.6% after purification. The specific activity was greater than 4 Ci/micromol. The labeled compound was stable for at least 120 hours in saline at 4 degrees C. It was initially in blood at 5 minutes with 4.79% of injected dose per g of tissue (%ID/g), and then dropped 0.33% ID/g at 24 hours. The uptake in liver, lung, and kidney at 4.44% ID/g, 2.03% ID/g, and 2.17% ID/g decreased with time, and less than 1% ID/g was measured after 24 hours in those organs. There was rapid tumor uptake, which reached 1.26% ID/g at 0.5 hours, the highest uptake at 8 hours. Yet, the [(131)I]iodo-17-AAG in the contralateral muscle was at a low level during the 48 hours. The tumor-contralateral muscle (T/CM) radioactivity ratio for [(131)I]iodo-17-AAG remained constant at all time points. [(131)I]iodo-17-AAG can be efficiently radiolabeled at high specific activity, purified by HPLC and stored with little radiolysis at this specific activities. [(131)I]iodo-17-AAG is a promising radiopharmaceutical in nuclear medicine, especially for tumor-targeted radionuclide brachytherapy.

  19. Therapeutical uses of 131I

    International Nuclear Information System (INIS)

    Lago, Graciela.

    1994-01-01

    Physiology of thyroid gland, pathology of thyroid , papillary, follicular cancer is considered together as differentiated thyroid cancer with very good results under therapy with iodine, invitro determination of calcitonin, search of metastasis, anaplastic carcinoma, as indifferentiated carcinoma with similar results as medullary carcinoma. This work gives a protocol for therapeutical use of 131I , in hyperthyroidism due to Graves-Basedow disease, thyrotoxic adenoma or Plummer disease, toxic multi nodular goiter, subacute thyroiditis. Is studied too the treatment with pharmaceuticals, surgery and radioactive iodine. A recommended use of each and protocol for iodine administration, fixed dose technique, dose estimation,absorbed dose, recommendations about when to use and not use 131I are included in this work

  20. 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)

  1. 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

  2. Preparation and biological evaluation of 111In-, 177Lu- and 90Y-labeled DOTA analogues conjugated to B72.3

    International Nuclear Information System (INIS)

    Mohsin, Huma; Fitzsimmons, Jonathan; Shelton, Tiffani; Hoffman, Timothy J.; Cutler, Cathy S.; Lewis, Michael R.; Athey, Phillip S.; Gulyas, Gyongyi; Kiefer, Garry E.; Frank, R. Keith; Simon, Jaime; Lever, Susan Z.; Jurisson, Silvia S.

    2007-01-01

    Three 1,4,7,10-tetraazacyclododecane-N,N',N '' ,N '' '-tetraacetic acid (DOTA) analogues were evaluated for relative in vivo stability when radiolabeled with 111 In, 90 Y and 177 Lu and conjugated to the monoclonal antibody B72.3. The DOTA analogues evaluated were 'NHS-DOTA' [N-hydroxysuccinimdyl (NHS) group activating one carboxylate], 'Arm-DOTA' (also known as MeO-DOTA; with a p-NCS, o-MeO-benzyl moiety on the methylene group of one acetic acid arm) and 'Back-DOTA' (with a p-NCS-benzyl moiety on a backbone methylene group of the macrocycle). The B72.3 was conjugated to the DOTA analogues to increase the retention time of the radioloabeled conjugates in vivo in mice. The serum stability of the various radiometalated DOTA conjugates showed them to have good stability out to 168 h (all >95% except 111 In-NHS-DOTA-B72.3, which was 91% stable). Hydroxyapatite stability for the 111 In and 177 Lu DOTA-conjugates was >95% at 168 h, while the 90 Y DOTA-conjugates were somewhat less stable (between 90% and 95% at 168 h). The biodistribution studies of the radiometalated DOTA-conjugates showed that no significant differences were observed for the 111 In and 177 Lu analogues; however, the 90 Y analogues showed lower stabilities, as evidenced by their increased bone uptake relative to the other two [2-20% injected dose per gram (% ID/g) for 90 Y and 2-8% ID/g for 111 In and 177 Lu]. The lower stability of the 90 Y analogues could be due to the higher beta energy of 90 Y and/or to the larger ionic radius of Y 3+ . Based on the bone uptake observed, the 177 Lu-NHS-DOTA-B72.3 had slightly lower stability than the 177 Lu-Arm-DOTA-B72.3 and 177 Lu-Back-DOTA-B72.3, but not significantly at all time points. For 90 Y, the analogue showing the lowest stability based on bone uptake was 90 Y-Arm-DOTA-B72.3, perhaps because of the metal's larger ionic radius and potential steric interactions minimizing effective complexation. The 111 In analogues all showed similar biological

  3. Evaluation of cell cycle changes activated by the administration of {sup 177}Lu-DOTA-antiCD20; Evaluacion de cambios en el ciclo celular activados por la administracion de {sup 177}Lu-DOTA-antiCD20

    Energy Technology Data Exchange (ETDEWEB)

    Ramos B, J. C.

    2016-07-01

    In the present project, cytometric evaluation of cell cycle changes induced by the {sup 177}Lu-DOTA-antiCD20 thermostatic radiopharmaceutical was performed, in which a cell culture of Raji cells from Burkitts lymphoma were used, which are CD20+; for flow cytometry different parameters were measured in which the cells were synchronized in G0/G1 and G2/M, to calculate the dose to nucleus that were given to the cells the Monte Carlo method was used at a dose interval from 1 to 5 Gy. The purpose of this work is to be able to observe by flow cytometry the arrest in the cell cycle with a lower dose interval than the one applied in other papers. (Author)

  4. {sup 177}Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Braeuer, Axel; Grubert, Lena Sophie; Roll, Wolfgang; Schaefers, Michael; Rahbar, Kambiz [University Hospital Muenster, Department of Nuclear Medicine, Muenster (Germany); Schrader, Andres Jan; Boegemann, Martin [University Hospital Muenster, Department of Urology, Muenster (Germany)

    2017-09-15

    Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with {sup 177}Lu-PSMA-617. Between December 2014 and January 2017, 59 consecutive patients (median age 72 years); interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee. The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1-7) of {sup 177}Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9-6.3 GBq). The median follow-up was 24 weeks (IQR 15-36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01). A PSA decline after the first cycle of {sup 177}Lu-PSMA-617

  5. 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.)

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

    International Nuclear Information System (INIS)

    Severi, Stefano; Sansovini, Maddalena; Ianniello, Annarita; Nicolini, Silvia; Caroli, Paola; Paganelli, Giovanni; Bodei, Lisa; Ibrahim, Toni; Di Iorio, Valentina; D'Errico, Vincenzo; Monti, Manuela

    2015-01-01

    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 177 Lu-DOTATATE (Lu-PRRT) in patients with GEP-NENs who relapsed after treatment with 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.)

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

    Directory of Open Access Journals (Sweden)

    Sandra Hermanto

    2016-10-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

    Koumarianou, Eftychia [Institute R-RP, NCSR ' Demokritos' , Athens (Greece); IAE, Radioisotope Centre POLATOM, 05-400 Swierk-Otwock (Poland)], E-mail: eytyxiak@yahoo.com; Mikolajczak, Renata; Pawlak, Dariusz [IAE, Radioisotope Centre POLATOM, 05-400 Swierk-Otwock (Poland); Zikos, Xhristos; Bouziotis, Pinelopi [Institute R-RP, NCSR ' Demokritos' , Athens (Greece); Garnuszek, Piotr; Karczmarczyk, Urszula; Maurin, Michal [Department of Radiopharmaceuticals, National Medicines Institute, Chelmska 30/34, 00-725 Warsaw (Poland); Archimandritis, Spyridon C. [Institute R-RP, NCSR ' Demokritos' , Athens (Greece)

    2009-08-15

    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-CONH{sub 2} (BN[2-14]NH{sub 2}), labeled with {sup 90}Y and {sup 177}Lu, 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-CONH{sub 2}), has already been studied and reported; however, the DOTA-chelated one, suitable for labeling with M{sup +3} type radiometals, was not yet described. Methods: The conditions for labeling of DOTA-BN[2-14]NH{sub 2} with noncarrier added {sup 90}Y and with {sup 177}Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide {sup 90}Y-DOTA-BN[2-14]NH{sub 2} and {sup 177}Lu-DOTA-BN[2-14]NH{sub 2} 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: {sup 90}Y-DOTA-BN[2-14]NH{sub 2} and {sup 177}Lu-DOTA-BN[2-14]NH{sub 2} were obtained with radiochemical yield >98% and high SA (67.3 GBq {sup 90}Y/{mu}mol and 33.6 GBq {sup 177}Lu/{mu}mol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH{sub 2} and both {sup nat}Y- and {sup nat}Lu-labeled analogs to GRP receptors were high (IC{sub 50}=1.78, 1.99, and 1.34 nM, respectively), especially for the {sup nat}Lu-DOTA-BN[2-14]NH{sub 2} complex. The cytotoxicity study of DOTA-BN[2-14]NH{sub 2} to PC-3 cells revealed an IC{sub 50}=6300 nM after 72 h of exposition, while the labeled derivatives showed no

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

    International Nuclear Information System (INIS)

    Koumarianou, Eftychia; Mikolajczak, Renata; Pawlak, Dariusz; Zikos, Xhristos; Bouziotis, Pinelopi; Garnuszek, Piotr; Karczmarczyk, Urszula; Maurin, Michal; Archimandritis, Spyridon C.

    2009-01-01

    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-CONH 2 (BN[2-14]NH 2 ), labeled with 90 Y and 177 Lu, 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-CONH 2 ), 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]NH 2 with noncarrier added 90 Y and with 177 Lu [specific activity (SA), 15 Ci/mg Lu] were investigated and optimized to provide 90 Y-DOTA-BN[2-14]NH 2 and 177 Lu-DOTA-BN[2-14]NH 2 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: 90 Y-DOTA-BN[2-14]NH 2 and 177 Lu-DOTA-BN[2-14]NH 2 were obtained with radiochemical yield >98% and high SA (67.3 GBq 90 Y/μmol and 33.6 GBq 177 Lu/μmol, respectively). They were stable when incubated in human serum for up to 24 h. The binding affinities of DOTA-BN[2-14]NH 2 and both nat Y- and nat Lu-labeled analogs to GRP receptors were high (IC 50 =1.78, 1.99, and 1.34 nM, respectively), especially for the nat Lu-DOTA-BN[2-14]NH 2 complex. The cytotoxicity study of DOTA-BN[2-14]NH 2 to PC-3 cells revealed an IC 50 =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 177 Lu-labeled peptide (84.87%) than for the 90 Y

  10. Evaluation of cell cycle changes activated by the administration of "1"7"7Lu-DOTA-antiCD20

    International Nuclear Information System (INIS)

    Ramos B, J. C.

    2016-01-01

    In the present project, cytometric evaluation of cell cycle changes induced by the "1"7"7Lu-DOTA-antiCD20 thermostatic radiopharmaceutical was performed, in which a cell culture of Raji cells from Burkitts lymphoma were used, which are CD20+; for flow cytometry different parameters were measured in which the cells were synchronized in G0/G1 and G2/M, to calculate the dose to nucleus that were given to the cells the Monte Carlo method was used at a dose interval from 1 to 5 Gy. The purpose of this work is to be able to observe by flow cytometry the arrest in the cell cycle with a lower dose interval than the one applied in other papers. (Author)

  11. In vivo biological evaluation of {sup 131}I radiolabeled-paclitaxel glucuronide ({sup 131}I-PAC-G)

    Energy Technology Data Exchange (ETDEWEB)

    Aslan, O.; Biber Muftuler, F.Z.; Yurt Kilcar, A.; Ichedef, C.; Unak, P. [Ege Univ., Izmir (Turkey). Dept. of Nuclear Applications

    2012-07-01

    Paclitaxel (PAC) is a natural occurring diterpene alkoloid originally isolated from the bark of Taxus Brevifolia. It is one of the most important antitumor agents for clinical treatment of ovarian, breast non-small cell lung and prostate cancers. It is known that these types of cancer cells have high {beta}-glucuronidase enzyme which can catalyze the hydrolysis of glucuronides. This is why the synthesis compounds which undergo glucuronidation come into question in the imaging and therapy of these cancer cells. The aim of current study is conjugation of glucuronic acid (G) to the starting substance PAC, labeling with {sup 131}I and to perform its in vivo biological evaluation. Glucuronic acid derived paclitaxel compound [paclitaxel-glucuronide (PAC-G)] was labeled with {sup 131}I using iodogen method. According to thin layer radio chromatography (TLRC) method, the radiochemical yield of {sup 131}I-PAC-G was 84.30 {+-} 7.40% (n=10). The biodistribution of {sup 131}I-PAC-G in healthy female and male Wistar Albino rats has been investigated. Imaging studies on male Balb-C mice were performed by using the Kodak FX PRO in vivo Imaging System. The range of the breast/blood, breast/muscle; ovary/blood, ovary/muscle ratios is approximately between 1.29 and 11.34 in 240 min, and between 0.71 and 8.24 in 240 min for female rats. The prostate/blood and prostate/muscle ratio is between 1.94 and 6.95 in 30 min for male rats. All these experimental studies indicate that {sup 131}I-PAC-G may potentially be used in breast, ovary and prostate tissues as an imaging agent. Also it is thought that {sup 131}I-PAC-G bears a therapy potential because of the {sup 131}I radionuclide and can be improved with further investigations. (orig.)

  12. Absorbed dose estimates from a single measurement one to three days after the administration of 177Lu-DOTATATE/-TOC.

    Science.gov (United States)

    Hänscheid, Heribert; Lapa, Constantin; Buck, Andreas K; Lassmann, Michael; Werner, Rudolf A

    2017-01-01

    To retrospectively analyze the accuracy of absorbed dose estimates from a single measurement of the activity concentrations in tumors and relevant organs one to three days after the administration of 177 Lu-DOTA-TATE/TOC assuming tissue specific effective half-lives. Activity kinetics in 54 kidneys, 30 neuroendocrine tumor lesions, 25 livers, and 27 spleens were deduced from series of planar images in 29 patients. After adaptation of mono- or bi-exponential fit functions to the measured data, it was analyzed for each fit function how precise the time integral can be estimated from fixed tissue-specific half-lives and a single measurement at 24, 48, or 72 h after the administration. For the kidneys, assuming a fixed tissue-specific half-life of 50 h, the deviations of the estimate from the actual integral were median (5 % percentile, 95 % percentile): -3 °% (-15 %>; +16 °%) for measurements after 24 h, +2 %> (-9 %>; +12 %>) for measurements after 48 h, and 0 % (-2 %; +12 %) for measurements after 72 h. The corresponding values for the other tissues, assuming fixed tissue-specific half-lives of 67 h for liver and spleen and 77 h for tumors, were +2 % (-25 %; +20 %) for measurements after 24 h, +2 °% (-16 %>; +17 %>) for measurements after 48 h, and +2 %> (-11 %>; +10 %>) for measurements after 72 h. Especially for the kidneys, which often represent the dose limiting organ, but also for liver, spleen, and neuroendocrine tumors, a meaningful absorbed dose estimate is possible from a single measurement after 2, more preferably 3 days after the administration of 177 Lu-DOTA-TATE/-TOC assuming fixed tissue specific effective half-lives. Schattauer GmbH.

  13. 177Lu labeling of Herceptin and preclinical validation as a new radiopharmaceutical for radioimmunotherapy of breast cancer

    International Nuclear Information System (INIS)

    Rasaneh, Samira; Rajabi, Hossein; Babaei, Mohammad Hossein; Daha, Fariba Johari

    2010-01-01

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

  14. In vitro and in vivo studies in Balb-c and nude mice of a new 177Lu-Bombesin analog developed for prostate tumor diagnosis and treatment

    International Nuclear Information System (INIS)

    Pujatti, Priscilla B.; Santos, Josefina S.; Couto, Renata M.; Araujo, Elaine B. de; Mengatti, Jair; Suzuki, Miriam F.

    2009-01-01

    In this work we describe the radiolabeling with 177 Lu and some properties of the novel bombesin analog BBNp6 - DOTA-X-BBN(6-14), where X is a spacer of six aminoacids. Bombesin (BBN) is an analog of human gastrin releasing peptide (GRP) isolated from the skin of the frog Bombina bombina in 1970. Development of radiolabeled BBN derivatives as agents for diagnostic imaging and systemic radiotherapy has increased considerable because of the observation that GRP receptors (GRPr) are over-expressed in a variety of human tumor cells, such as prostate tumor cells. 177 Lu-labeled peptides are attractive due to the excellent radiophysical properties and commercial availability of the radiometal. BBNp6 was labeled with high yield after reacting with 92.5 MBq of 177 LuCl3 at 90 deg C for 30 minutes and this mixture kept stable for more than 96 hours at 4 deg C and 1 hour in human plasma. In vivo studies showed a multicompartimental distribution model with fast blood clearance, mainly performed by renal pathway. In addition, 177 Lu-BBNp6 showed high affinity for PC-3 tumor xenografts, but not for pancreas and intestine (GRP positive tissues), suggesting its specificity and usefulness for prostate tumor treatment. Moreover, scintigraphic images showed that this derivative can also be a tool in this tumor diagnosis. So, BBNp6 is a promising radiopharmaceutical for prostate tumor imaging and treatment. (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)

    Vilchis J, A.

    2010-01-01

    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 177 Lu and to evaluate their in vitro and in vivo stability as potential specific therapeutic radiopharmaceuticals. Labelled was carried out by direct reaction of 177 LuCl 3 with c-DOTA-RGD peptides in 1 M acetate buffer ph 5.5 at 90 o C for 30 min. Radiochemical purity and stability studies were realized by reversed phase HPLC and I TLC-Sg analyses in human serum and saline solution. Biological recognition was performed using MCF7 tumor cells (positive 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. 177 Lu-DOTA-RGD and 177 Lu-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. 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)

    Caldeira Filho, Jose de Souza

    2009-01-01

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

  17. Somatostatin-receptor-targeted α-emitting 213Bi is therapeutically more effective than β--emitting 177Lu in human pancreatic adenocarcinoma cells

    International Nuclear Information System (INIS)

    Nayak, Tapan K.; Norenberg, Jeffrey P.; Anderson, Tamara L.; Prossnitz, Eric R.; Stabin, Michael G.; Atcher, Robert W.

    2007-01-01

    Introduction: Advance clinical cancer therapy studies of patients treated with somatostatin receptor (sstr)-targeted [DOTA 0 -Tyr 3 ]octreotide (DOTATOC) labeled with low-linear-energy-transfer (LET) β - -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 α-emitting 213 Bi to that of low-LET β - -emitting 177 Lu by determining relative biological effectiveness (RBE) using the external γ-beam of 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 213 Bi and 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 PLUS 10x kit. Results: Using equimolar DOTATOC treatment with concurrent irradiation with a 137 Cs source as reference radiation, the calculated RBE of [ 213 Bi]DOTATOC was 3.4, as compared to 1.0 for [ 177 Lu]DOTATOC. As measured in terms of absorbance units, [ 213 Bi]DOTATOC caused a 2.3-fold-greater release of apoptosis-specific mononucleosomes and oligonucleosomes than [ 177 Lu]DOTATOC at the final treatment time of 96 h (P 213 Bi]DOTATOC is therapeutically more effective in decreasing survival than is [ 177 Lu]DOTATOC in human pancreatic adenocarcinoma cells due to its comparatively higher RBE

  18. Standardization of Procedures for the Preparation of (177)Lu- and (90)Y-labeled DOTA-Rituximab Based on the Freeze-dried Kit Formulation.

    Science.gov (United States)

    Wojdowska, Wioletta; Karczmarczyk, Urszula; Maurin, Michal; Garnuszek, Piotr; Mikołajczak, Renata

    2015-01-01

    Rituximab when radiolabelled with (177)Lu or (90)Y has been investigated for the treatment of patients with Non-Hodgkin's Lymphoma. In this study, we optimized the preparation of antibody conjugates with chelating agent in the freeze-dried kit. It shortens procedures needed for the successful radiolabeling with lutetium-177 and yttrium-90 and assures reproducible labelling yields. Various molar ratios of Rituximab:DOTA (from 1:5 to 1:100) were used at the conjugation step and different purification method to remove unbound DOTA were investigated (size-exclusion chromatography, dialysis, ultrafiltration). The final monoclonal antibody concentration was quantified by Bradford method, and the number of DOTA molecules was determined by radiolabeling assay using (64)Cu. The specific activity of (177)Lu-DOTA-Rituximab and (90)Y-DOTA-Rituximab were optimized using various amounts of radiometal. Quality control (SE-HPLC, ITLC) and stability study were performed. An average of 4.2 ± 0.8 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab. The ultrafiltration system was the most efficient for purification and resulted in the highest recovery efficiency (77.2%). At optimized conditions the (177)Lu-DOTARituximab and (90)Y-DOTA-Rituximab were obtained with radiochemical purity >99% and specific activity ca. 600 MBq/mg. The radioimmunoconjugates were stable in human serum and 0.9% NaCl. After 72 h of incubation the radiochemical purity of (177)Lu-DOTA-Rituximab decreased to 94% but it was still more than 88% for (90)Y-DOTA-Rituximab. The radioimmunoconjugate showed stability after six months storage at 2 - 8(0)C, as a lyophilized formulation. Our study shows that Rituximab-DOTA can be efficiently radiolabeled with (177)Lu and (90)Y via p-SCN-Bn-DOTA using a freezedried kit.

  19. Fast GPU-based Monte Carlo code for SPECT/CT reconstructions generates improved 177Lu images.

    Science.gov (United States)

    Rydén, T; Heydorn Lagerlöf, J; Hemmingsson, J; Marin, I; Svensson, J; Båth, M; Gjertsson, P; Bernhardt, P

    2018-01-04

    Full Monte Carlo (MC)-based SPECT reconstructions have a strong potential for correcting for image degrading factors, but the reconstruction times are long. The objective of this study was to develop a highly parallel Monte Carlo code for fast, ordered subset expectation maximum (OSEM) reconstructions of SPECT/CT images. The MC code was written in the Compute Unified Device Architecture language for a computer with four graphics processing units (GPUs) (GeForce GTX Titan X, Nvidia, USA). This enabled simulations of parallel photon emissions from the voxels matrix (128 3 or 256 3 ). Each computed tomography (CT) number was converted to attenuation coefficients for photo absorption, coherent scattering, and incoherent scattering. For photon scattering, the deflection angle was determined by the differential scattering cross sections. An angular response function was developed and used to model the accepted angles for photon interaction with the crystal, and a detector scattering kernel was used for modeling the photon scattering in the detector. Predefined energy and spatial resolution kernels for the crystal were used. The MC code was implemented in the OSEM reconstruction of clinical and phantom 177 Lu SPECT/CT images. The Jaszczak image quality phantom was used to evaluate the performance of the MC reconstruction in comparison with attenuated corrected (AC) OSEM reconstructions and attenuated corrected OSEM reconstructions with resolution recovery corrections (RRC). The performance of the MC code was 3200 million photons/s. The required number of photons emitted per voxel to obtain a sufficiently low noise level in the simulated image was 200 for a 128 3 voxel matrix. With this number of emitted photons/voxel, the MC-based OSEM reconstruction with ten subsets was performed within 20 s/iteration. The images converged after around six iterations. Therefore, the reconstruction time was around 3 min. The activity recovery for the spheres in the Jaszczak phantom was

  20. On the conversion of the high multipole transition between the 23/2- 3qp state and the 17/2+ rotational state in 177Lu

    International Nuclear Information System (INIS)

    Deepa, S.; Vijay Sai, K.; Ashish, T.; Venkataramaniah, K.; Kailas, S.

    2012-01-01

    Gerl et al through a compilation of Internal Conversion Coefficients (ICCs) of high multipole transitions and a comparison with various theoretical calculations and experimental data concluded that the theoretical values of BRICC are close to experimental values within 1-2% when compared to Hager and Seltzer and Rosel et al values. In a programme supported through a DAE BRNS project, we have been trying to experimentally determine the ICCs of high multipole transitions with high precision to garner support and evidence for the findings of Gerl et al. The present measurement is a part of such an effort. The prolate deformed nucleus 177 Lu lies in the rare earth region with Z = 71 and N = 106 between closed shells. Several three-quasiparticle states as well as states originating from the coupling of a quasi-particle to the γ-vibration of the core were established in 177 Lu at energies above 1200 keV by different groups

  1. 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

  2. Gamma-ray impurities of {sup 111}In, {sup 201}Tl, {sup 177}Lu and {sup 99m}Tc determined by means of a HPGE spectrometer

    Energy Technology Data Exchange (ETDEWEB)

    Koskinas, Marina F.; Almeida, Jamille da Silveira; Moreira, Denise Simões; Semmler, Renato; Dias, Mauro da Silva, E-mail: koskinas@ipen.br, E-mail: jamillealmeida@gmail.com, E-mail: denise.moreira@ipen.br, E-mail: rsemmler@ipen.br, E-mail: msdias@ipen.br [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil)

    2017-11-01

    This work aims to present the radioactive impurities gamma rays emitters detected in some radiopharmaceuticals widely applied to diagnosis and therapy purposes, supplied to nuclear medicine services in Brazil by the Radiopharmaceutical Center(CR) of Nuclear and Energy Research Institute, IPEN, in São Paulo. The analysis was undertaken by means of an HPGe gamma spectrometer. The radiopharmaceuticals analyzed were: {sup 111}In, {sup 201}Tl, {sup 177}Lu and {sup 99m}Tc. (author)

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

    Science.gov (United States)

    2014-09-01

    Irene Karpenko Lauren Tyrell Olivera Calukovic Gillian Hodes June Greenberg Jessica Campbell PATIENTS AND THEIR FAMILIES Biostatistics...myelosuppression or need for >2 platelet (plt) transfusions, febrile neutropenia , or grade >2 non-heme toxicity following 177Lu- J591. PSA was assessed prior to...toxicity • Grade 4 neutropenia or thrombocytopenia > 14 days • Need for > 2 platelet transfusions or hemorrhage • Febrile neutropenia • > 3 week delay for

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

    Science.gov (United States)

    2017-09-01

    on a federally funded study (as compared to pharmaceutical -sponsored). Therefore, after discussions with the site PI’s, additional key opinion...location (printed) APPENDIX C iv SCHEMA Informed Consent Screening Labs (CBC, chemistry, PSA, testosterone), CT/ MRI abd/pelvis, bone scan, CXR...111In-J591, continue ketoconazole, J591 scan Infusion of 177Lu-J591 x1, continue ketoconazole, J591 scan CT/ MRI abd/pelvis, bone scan, CXR q 6

  5. 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)

  6. Mono(pyridine-N-oxide) DOTA analog and its G1/G4-PAMAM dendrimer conjugates labeled with 177Lu: Radiolabeling and biodistribution studies

    International Nuclear Information System (INIS)

    Laznickova, A.; Biricova, V.; Laznicek, M.; Hermann, P.

    2014-01-01

    177 Lu radiolabeling of the first (G1-) or fourth (G4-) generation polyaminoamide (PAMAM) dendrimer conjugates with DOTA-like bifunctional chelator with one methylenepyridine-N-oxide pendant arm (DO3A-py NO-C ) stability of the radiolabeled species and their pharmacokinetic characteristics were evaluated in preclinical experiments. The results showed that the G1- and G4-dendrimer conjugates, modified in average with 7.5 or 57 DO3A-py NO-C chelating units, respectively, can also be labeled with 177 Lu with a high specific activity and radiochemical purity even at 37 °C. The radiolabeled species were stable for at least 24 h. Distribution profile of G1-dendrimer conjugate in organs and tissues of rats was more favorable than that of G4 one. On the other hand, the later dendrimer conjugate bears a substantially higher number of metal chelators per molecule enabling binding of a considerably larger number of radiometals. Our results indicate that an employment of dendrimer-chelate conjugates with bound radiometals might represent a prospective way for radiolabeling of biologically active target-specific macromolecules to obtain markedly high specific activity. - Highlights: • Chelation of DOTA-like ligands suitable for biomacromolecules modification. • Radiolabeling of modified PAMAM-dendrimers with 177 Lu. • Determination of stability of the labeled conjugates. • Pharmacokinetic characteristics evaluated in preclinical experiments

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

    Energy Technology Data Exchange (ETDEWEB)

    Vilchis J, A.

    2010-07-01

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

  8. Observation of radioactive iodine ({sup 131}I, {sup 129}I) in cropland soil after the Fukushima nuclear accident

    Energy Technology Data Exchange (ETDEWEB)

    Fujiwara, Hideshi, E-mail: hfuji@affrc.go.jp

    2016-10-01

    During the early stages of the Fukushima nuclear accident, the temporal variations of {sup 131}I deposited on the ground and of {sup 131}I accumulated in cropland soil were monitored at a fixed location in Japan. Moreover, concentrations of long-lived radioactive iodine ({sup 129}I) in atmospheric deposits and soil were measured to examine the feasibility of retrospectively reconstructing {sup 131}I levels from the levels of accident-derived {sup 129}I. The exceptionally high levels of {sup 131}I in deposits and soil were attributed to rainfall-related deposition of radionuclides. In the crop field studied, the losses of deposited {sup 131}I and {sup 129}I due to volatilization were small. The atomic ratio {sup 129}I/{sup 131}I in the topsoil corresponded to the same ratio in deposits. The {sup 131}I concentrations measured in the topsoil were very consistent with the {sup 131}I concentrations reconstructed from the {sup 129}I concentrations in the soil. - Highlights: • A high level of {sup 131}I contamination occurs through rainfall-related deposition. • Only a small loss of deposited radioactive iodine occurs via volatilization. • The {sup 129}I/{sup 131}I ratio in soil corresponds to the ratio in atmospheric deposit. • The feasibility of retrospectively reconstructing {sup 131}I is confirmed.

  9. {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

  10. Evaluation of (68)Ga- and (177)Lu-DOTA-PEG4-LLP2A for VLA-4-Targeted PET Imaging and Treatment of Metastatic Melanoma.

    Science.gov (United States)

    Beaino, Wissam; Nedrow, Jessie R; Anderson, Carolyn J

    2015-06-01

    Malignant melanoma is a highly aggressive cancer, and the incidence of this disease is increasing worldwide at an alarming rate. Despite advances in the treatment of melanoma, patients with metastatic disease still have a poor prognosis and low survival rate. New strategies, including targeted radiotherapy, would provide options for patients who become resistant to therapies such as BRAF inhibitors. Very late antigen-4 (VLA-4) is expressed on melanoma tumor cells in higher levels in more aggressive and metastatic disease and may provide an ideal target for drug delivery and targeted radiotherapy. In this study, we evaluated (177)Lu- and (68)Ga-labeled DOTA-PEG4-LLP2A as a VLA-4-targeted radiotherapeutic with a companion PET agent for diagnosis and monitoring metastatic melanoma treatment. DOTA-PEG4-LLP2A was synthesized by solid-phase synthesis. The affinity of (177)Lu- and (68)Ga-labeled DOTA-PEG4-LLP2A to VLA-4 was determined in B16F10 melanoma cells by saturation binding and competitive binding assays, respectively. Biodistribution of the LLP2A conjugates was determined in C57BL/6 mice bearing B16F10 subcutaneous tumors, while PET/CT imaging was performed in subcutaneous and metastatic models. (177)Lu-DOTA-PEG4-LLP2A showed high affinity to VLA-4 with a Kd of 4.1 ± 1.5 nM and demonstrated significant accumulation in the B16F10 melanoma tumor after 4 h (31.5 ± 7.8%ID/g). The tumor/blood ratio of (177)Lu-DOTA-PEG4-LLP2A was highest at 24 h (185 ± 26). PET imaging of metastatic melanoma with (68)Ga-DOTA-PEG4-LLP2A showed high uptake in sites of metastases and correlated with bioluminescence imaging of the tumors. These data demonstrate that (177)Lu-DOTA-PEG4-LLP2A has potential as a targeted therapeutic for treating melanoma as well as other VLA-4-expressing tumors. In addition, (68)Ga-DOTA-PEG4-LLP2A is a readily translatable companion PET tracer for imaging of metastatic melanoma.

  11. Indirect and direct measurement of thermal neutron acceleration by inelastic scattering on the {sup 177}Lu isomer

    Energy Technology Data Exchange (ETDEWEB)

    Belier, G.; Roig, O.; Meot, V.; Daugas, J.M. [CEA Bruyeres-le-Chatel, Dept. de Physique Theorique et Appliquee, 91 (France); Aupiais, J.; Jutier, Ch.; Le Petit, G. [CEA Bruyeres-le-Chatel, Service de Physique Nucleaire, 91 (France). Dept. de Physique Theorique et Appliquee; Letourneau, A.; Marie, F. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, Service de Physique Nucleaire, 91- Gif sur Yvette (France); Veyssiere, Ch. [CEA Saclay, Dept. d' Astrophysique de Physique des Particules, de Physique Nucleaire et de l' Instrumentation Associee, Service d' Ingenierie des Systemes, 91- Gif sur Yvette (France)

    2008-07-01

    When neutrons interact with isomers, these isomers can de-excite and in such a reaction the outgoing neutron has an energy greater than the in-going one. This process is referred as Inelastic Neutron Acceleration or Super-elastic Scattering. Up to now this process was observed for only two nucleus, {sup 152m}Eu and {sup 180m}Hf by measuring the number of fast neutrons produced by isomeric targets irradiated with thermal neutrons. In these experiments the energies of the accelerated neutrons were not measured. This report presents an indirect measurement of inelastic neutron acceleration on {sup 177m}Lu, based on the burn-up and the radiative capture cross sections measurements. Since at thermal energies the inelastic scattering and the radiative capture are the only processes that contribute to the isomer burn-up, the inelastic cross section can be deduced from the difference between the two measured quantities. Applying this method for the {sup 177}Lu isomer with different neutron fluxes we obtained a value of (257 {+-} 50) barns (for a temperature of 323 K) and determined that there is no integral resonance for this process. In addition the radiative capture cross section on {sup 177g}Lu was measured with a much better accuracy than the accepted value. Since the acceleration cross section is quite high, a direct measurement of this process was undertaken, sending thermal neutrons and measuring the fast neutrons. The main goal now is to measure the outgoing neutron energies in order to identify the neutron transitions in the exit channel. In particular the K conservation question can be addressed by such a measurement. (author)

  12. Intercomparison of 131I activity measurements in nuclear medicine

    International Nuclear Information System (INIS)

    Kim, G. Y.; Yang, H. K.; Lim, C. I.; Lee, H. K.; Jeong, H. K.

    2004-01-01

    Activity measurements in nuclear medicine using a dose calibrator have been performed for several decades and their reliability has varied. To minimise the radiation dose to patients with radionuclides, it is necessary to ensure that the sample administered is accurately assayed. Recognizing the importance of intercomparison in nuclear medicine and the need to make access to activity standards traceable to the international measurement system, the KFDA, as a national secondary standard dosimetry laboratory (SSDL), started an intercomparison program in 2002. This program was initiated by survey to all nuclear medicine centres regarding general information about their dose calibrators, radioisotopes etc. 71 nuclear medicine centres (79 dose calibrators) participated in the intercomparison program with 131 I isotope. To assess the accuracy of clinical measurements of the activity of 131 I solutions and to determine the reason for the disagreement, an intercomparison was conducted using 4 ml aliquots in 10 ml P6 vial with a total activity in the region of 10 -20 MBq. The reference time of decay for all solutions was 0:00 on 25 September 2002. The half-life used was 8.04 days. For the evaluation of solution in KFDA, a sealed, high pressure and re-entrant ionisation chamber, NPL-CRC radionuclide calibrators were used. The verification of our calibration quality was by means of a comparison with the Korea Primary Standard Laboratory (KRISS). The activity ratio of KFDA to KRISS for the 131 I solutions is 1.011. The difference between the value quoted by the clinic, A hospital and the value obtained by the KFDA, A KFDA , is expressed as a percent deviation, i.e. DEV(%) 100x(A hospital -A KFDA )/A KFDA . From the data obtained it was found that 61% of the calibrators showed a deviation within +/-5%; 23% had a deviation in the range 5% 131 I solution activity measurements, using dose calibrators in Koreas, and also to provide the participants with a traceable standard to

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

    International Nuclear Information System (INIS)

    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

  14. Quality control procedures for iodinated radiopharmaceuticals 131I-Hippuran and 131I-Risa

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Pereira, N.P.S. de; Silva, C.P.G. da.

    1986-02-01

    A rapid miniaturized chromatography system was developed for fast determination of the proportion of inorganic radioactive iodide from radiopharmaceutical 131 I-Hippuran and 131 I-Risa. The technical parameters associated with miniaturized chromatography system were evaluated. One of the problems found in this system was the movement of the 131 I-Risa from the origin with consequent overestimation of the inorganic iodide. A correct spot placement eliminated this problem. (Author) [pt

  15. Hypothyroidism following 131I therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Kubo, Atsushi; Kondo, Makoto; Kinoshita, Fumio; Maekawa, Akira; Okamoto, Jiro.

    1977-01-01

    Of 890 patients who received 131 I therapy for hyperthyroidism, the results of therapy were examined on 584 who could be followed up. Of these 502 (86%), were sured including 3 patients who had been completely healed after recurrence, 9 patients are still under medical treatment, and 10 died. The incidence of hypothyroidism following 131 I therapy was 1.6% after 1 year, 2.3% after 2 years, 4.7% after 5 years, 15.0% after 10-12 years, 22.1% after 13-15 years and 27.5% after 16-20 years. The incidence increased constantly with the passage of time. Factors influencing the response to treatment have been investigated. As a consequence, the number of rads delivered to the thyroid gland, the gland size, and previous surgery correlated with the incidence of hypothyroidism. The number of doses of 131 I, uptake and half-life of 131 I in the thyroid, previous antithyroid medication, time between the onset of hyperthyroid symptoms and 131 I therapy, and the age or sex of the patients appeared unrelated. The times taken to become euthyroid following a single dose of 131 I were 5.6 months with 2000-4000 rads, 4.4 months with 4001-7000 rads, 4.2 months with 7001-10000 rads and 3.5 months with more than 10001 rads. The time was prolonged with decrease of rads delivered to the thyroid gland. It was found that the patients who passed through a transient hypothyroid phase in the period of three to four months after administration of 131 I had a high incidence of late permanent hypothyroidism. (Evans, J.)

  16. The bioconcentration of 131I in fresh water fish

    International Nuclear Information System (INIS)

    Yu, K.N.; Cheung, T.; Young, E.C.M.; Luo, D.L.

    1996-01-01

    The dynamic characteristics of the radionuclide concentration process in fresh water fish have been studied. The experimental data for the tilapias were fitted using a simple compartment model to get characteristics parameters such as concentration factors, elimination rate constants, and initial concentration rates, which are 3.08 Bq kg -1 /Bq L -1 , 0.00573 h -1 , and 12.42 Bq kg -1 h -1 , respectively. The relative concentrations of 131 I in different parts, i.e., head, gills, flesh, bone and internal organs, of the tilapias are also determined, which are found to be 10.8, 15.4, 26.1, 11.0, and 37.0%, respectively. The effects of different factors on the transfer of radionuclides in fresh water fishes are also discussed. Experiments on the tilapias and the common carp show that the variation of concentration factors for different species may be significant even for the same radionuclide and the same ecological system. On the other hand, the variation in the concentration factors for the flesh of the tilapias is not significant for a certain range of 131 I concentrations in the water. 12 refs., 1 fig., 1 tab

  17. Investigation of therapeutic efficiency of phenytoin (PHT) labeled with radioactive 131I in the cancer cell lines

    International Nuclear Information System (INIS)

    Cansu Uzaras; Ugur Avcibasi; Hasan Demiroglu; Emin Ilker Medine; Ayfer Yurt KiIcar; Fazilet Zuemruet Biber Mueftueler; Perihan Uenak

    2016-01-01

    The aim of this study is to determine the incorporations of PHT radiolabeled with 131 I ( 131 I-PHT) on U-87 MG, Daoy and A549 cancerous cell lines. For this, cold and radio-labeling studies were carried out. The radiolabeling yield of 131 I-PHT was obtained about 95 %. Subsequently, cell culture studies were carried out and radio-labeling yields of 131 I, 131 I-PHT on U-87 MG, Daoy and A549 cancerous cells were investigated. Cell culture studies demonstrated that the incorporation values of 131 IPHT on the three cell lines decreased with increasing radioactivity. Consequently, 131 I-PHT may be a good radiopharmaceutical for targeting radionuclide therapy of Central Nervous System Tumors. (author)

  18. A comparison of 2D and 3D kidney absorbed dose measures in patients receiving 177Lu-DOTATATE

    Directory of Open Access Journals (Sweden)

    Kathy Willowson

    2018-06-01

    Full Text Available Objective(s: To investigate and compare quantitative accuracy of kidney absorbed dose measures made from both 2D and 3D imaging in patients receiving 177LuDOTATATE (Lutate for treatment of neuroendocrine tumours (NETs. Methods: Patients receiving Lutate therapy underwent both whole body planar imaging and SPECT/CT imaging over the kidneys at time points 0.5, 4, 24, and 96-120 hours after injection. Planar data were corrected for attenuation using transmission data, and were converted to units of absolute activity via two methods, using either a calibration standard in the field of view or relative to pre-voiding image total counts. Hand drawn regions of interest were used to generate time activity curves and kidney absorbed dose estimates in OLINDA-EXM. Fully quantitative SPECT data were generated using CT-derived corrections for both scatter and attenuation, before correction for dead time and application of a camera specific sensitivity factor to convert data to units of absolute activity. Volumes of interest were defined for kidney using the co-registered x-ray CT, before time activity curves and absorbed dose measures were generated in OLINDA-EXM, both with and without corrections made to the model for patient specific kidney volumes. Quantitative SPECT data were also used to derive dose maps through dose kernel convolution (DKC, which was treated as the gold standard. Results: A total of 50 studies were analysed, corresponding to various cycles of treatment from 21 patients. Planar absorbed dose estimates were consistently higher than SPECT derived estimates by, on average, a factor of 3. Conclusion: Quantitative SPECT is considered the gold standard approach for organ specific dosimetry however often relies on in house software. As such planar methods for estimating absorbed dose are much more widely available, and in particular, are often the only source of reference in previously published data. For the case of Lutate dosimetry, planar

  19. 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)

    Melis, M.; Swart, J. de; Groen, H.C.; Konijnenberg, M.W.; Van der Graaf, L.M.; Kaemmerer, D.; Kulkami, H.R.; Baum, R.P.; Lupp, A.; Saenger, J.; Jong, M. de

    2015-01-01

    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 68 Ga-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 177 Lu-DOTA-octreotate. Methods: a patient diagnosed with neuroendocrine neoplasm of the pancreatic tail (SUV max on 68 Ga-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 177 Lu-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 111 In-DOTA-octreotate in-vitro autoradiography after decay of 177 Lu. 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: 177 Lu-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 177 Lu). The

  20. The impact of repeated cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617 on renal function in patients with hormone refractory metastatic prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    Yordanova, Anna; Becker, Anja; Eppard, Elisabeth; Kuerpig, Stefan; Essler, Markus; Ahmadzadehfar, Hojjat [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fisang, Christian [University Hospital Bonn, Department of Urology, Bonn (Germany); Feldmann, Georg [University Hospital Bonn, Department of Internal Medicine, MED3, Bonn (Germany)

    2017-08-15

    [{sup 177}Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [{sup 177}Lu]Lu-PSMA-617 were investigated. Renal function was assessed through laboratory tests (creatinine, GFR, cystatin C) and Tc-99 m-MAG3 measurements. Adverse events were classified according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0. To identify risk factors for renal toxicity, we used Pearson's correlation coefficient and the corresponding p values. None of the 55 patients experienced severe nephrotoxicity (grade 3/4). In 14 patients (25%), we observed increased creatinine levels of CTC 1 or 2 . There were 16 cases of increased GFR (grade 1/2). At the baseline, only 14 patients had elevated cystatin C. However, post-therapeutic cystatin C was elevated in 32 patients (58%). A significant effect on renal function was found for age (p = 0.049), hypertension (p = 0.001) and pre-existing kidney disease (p = 0.001). The most reliable predictive markers of nephrotoxicity were TER-MAG3 and cystatin C. Renal toxicity in patients treated with [{sup 177}Lu]Lu-PSMA-617 was low. There was no (sub)acute grade 3 or 4 nephrotoxicity. (orig.)

  1. National comparison of activity measurements of 131I, 60Co, and 133Ba in Indonesia

    International Nuclear Information System (INIS)

    Wurdiyanto, Gatot; Marsoem, Pujadi; Widodo, Susilo; Iskandar, Dadong; Muhayatun; Hartoyo, Unggul; Sugino; Gede Sutresna, I.; Hutabarat, Tommy; Suparman, Ibon; Purwanto, Setyo

    2014-01-01

    National comparisons of radioactivity measurements of 131 I and 60 Co (in 2010) and of 133 Ba (in 2011) were carried out within the framework of the National Radiation Metrology Laboratory Program of Indonesia, coordinated by PTKMR-BATAN. Eleven laboratories took part in the comparison, and all measurements were made using gamma spectrometry, on point sources with an activity between 2000 Bq and 6000 Bq. Several laboratories reported values which were more than 10% different from the reference value for 131 I and 133 Ba. Possible reasons for these differences are discussed. This program will be continued with other radionuclides to maintain and control quality assurance for the local laboratories. - Highlights: • PTKMR-BATAN coordinated national comparison of 131 I, 60 Co and 133 Ba. • Eleven laboratories took part in the comparison. • All measurements were done using gamma spectrometry methods. • For 131 I and 133 Ba, 3 laboratories have more than 10% difference from reference laboratory value

  2. Radiological protection guidance for radioactive patients -new data for therapeutic 131I

    International Nuclear Information System (INIS)

    Hilditch, T.E.; Watson, W.S.; Connell, J.M.C.; Davies, D.L.; Alexander, W.D.

    1991-01-01

    Thyroidal retention of 131 I was measured in 77 thyrotoxic patients over a period of 1-50 days after a first therapeutic administration of the radionuclide. Mean 131 I activity in the gland (± S.D.) at 1 day was 56.1 ± 11.1% of the administered dose activity and thereafter retention followed a single exponential decay pattern with a mean effective half-life (± S.E.M.) of 6.35 ± 0.14 days. In patients who required further 131 I therapy, there was evidence that retention could be markedly reduced if there was virtual ablation of thyroid tissue. It is proposed that these retention data can be used to determine body radioactivity at any interval after the administration of 131 I for treatment of thyrotoxicosis, thus obviating the need for serial measurements in every individual patient. (author)

  3. Vertical migration of 85Sr, 137Cs and 131I in various arable and undisturbed soils

    International Nuclear Information System (INIS)

    Palagyi, S.; Palagyiova, J.

    2003-01-01

    The vertical migration of 85 Sr, 137 Cs and 131 I in some arable and undisturbed single-contaminated soils was studied by gamma-spectrometry measurements under lysimetric laboratory conditions during irrigation of the soil profiles with wet atmospheric precipitation for about one year, except 131 I. A new simple exponential compartment (box) model was derived, which makes it possible to calculate the migration rate constants and migration rates in the individual soil layers (vertical sections) as well as the total vertical migration rate constants and total vertical migration rates of radionuclides in the bulk soil horizon. The relaxation times of radionuclides in respective soil horizons can also be evaluated. (author)

  4. Labelling of tung oil with 131I

    International Nuclear Information System (INIS)

    Correia, R.J.; Mitta, A.E.A.

    1975-01-01

    A method for labelling Tung Oil with 131 I is described. The oil is dissolved in peroxide free, dry ethyl ether and then it is treated with 131 ICl. A 2,5% mercuric acetate solution in glacial acetic acid is added as a catalist. A radiochemical yield of 100% is achieved in 20 minutes. (author)

  5. Therapy of hyperthyroidism with Na131I

    International Nuclear Information System (INIS)

    Kakehi, Hirotake; Furukawa, Takashi; Fukakusa, Shunichi; Futonaka, Hiroshi; Takahashi, Yuji

    1984-01-01

    Forty one patients of hyperthyroidism were treated with Na 131 I. Men and women are in the ratio 1:3.1. The ages of patients are between twenties and sixties and the forties are the highest in number. The observation period of clinical courses is between 1 and 8 years. The number of patients observed over 5 years are 51% of them and over 2 years are 83%. The treatment frequency is as follows: On 37 cases each one was treated once with Na 131 I. 2 cases twice, 1 case at 4 times in 3 years and 1 case at 5 times in 6 years. The treatment doses are between 4,000-6,000 rad (40-60 Gray). In the cases treated with the irradiation dose of 6,000 rad, we often saw hypothyroidism. In cases aiming 4,000-5,000 rad, there is a tendency of leaving hyperthyroidism unrecovered. In conclusion, the patients should be treated giving 4,000-5,000 rad or with Na 131 I doses of 3-6mCi. If the effects of the treatment are insufficient, the patients should be further treated with anti-thyroid drug or treated again with Na 131 I. As the result, there are at present 25 cases (61.0%) in normal status of the thyroid gland, 12 cases (29.2%) in hyperthyroidism and 4 cases (9.8%) in hypothyroidism totaling 41 cases in all. (author)

  6. 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.

  7. Radioiodine 131I metabolism in human

    International Nuclear Information System (INIS)

    Mori, Toru

    1976-01-01

    Metabolic fate of orally administered 131 I in human was studied. Chronological observations of whole body radioactivity distribution and thyroid 131 I uptake curve revealed that 131 I metabolism was greatly affected by the amount of dietary iodine intake. Under the high iodine intake exceeding 1 mg per day, uptake curve showed biphasic descending type, that is, rapid accumulation during 3 to 6 hours and rapid fall up to 48 hours and gradual decrease afterwards. While, ascending type, monophasic and maximal at 24 hours, was found universary under low iodine intake less than 500 μg per day. Thyroid function should not be affected by the amount of iodine intake, and we analysed 131 I metabolism using a new four compartments which included intrathyroidal inorganic iodine pool. The results, especially hormone production rate, were found quite useful even under high iodine intake. Thyroidal organic iodine contents were calculated as approximately 2.5 mg and this value was much less than previously reported values from other countries. Administered radioiodine were mixed up with stable body iodine and reached equilibration by around 10 days. From seroimmunological, histological (microscopic and electron microscopic) studies, and irradiation studies to the cultured human thyroid cells, we concluded that this unexpected phenomenon was derived from chromosomal damage which induced gradual decrease in cell population because of inability to reproduce. Carcinogenic and genetic effects were not serious, and only three leukemic patients were reported in this country and 484 normal babies were born from 7,500 treated parents. Thus, therapeutic dose of 131 I was proved rather safe, and even when exposed to radioiodine, administration of perchlorate or thiocyanate, excessive iodine and TSH seemed effective to avoid radiation injuries. (auth.)

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

    Science.gov (United States)

    Basu, Sandip; Abhyankar, Amit

    2014-12-01

    This report describes a case of extensive diffuse bone marrow involvement with bilateral breast metastases from duodenal neuroendocrine tumor giving rise to a superscan-like appearance on somatostatin receptor-targeted (99m)Tc-hydrazinonicotinamide-TOC scintigraphy. The metastatic lesions demonstrated partial concordance with (18)F-FDG PET/CT findings, signifying varying tumor biology and heterogeneity among metastatic lesions in the same individual, as illustrated with a dual-tracer approach. There was a dramatic symptomatic and biochemical response and better health-related quality of life with a single fraction of peptide receptor radionuclide therapy with (177)Lu-DOTATATE, and radiologically there was stable disease at that point. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  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. Sequelae and survivorship in patients treated with (131)I-MIBG therapy.

    Science.gov (United States)

    Sze, W C C; Grossman, A B; Goddard, I; Amendra, D; Shieh, S C C; Plowman, P N; Drake, W M; Akker, S A; Druce, M R

    2013-08-06

    (131)I-meta-iodobenzylguanidine ((131)I-MIBG) has been in therapeutic use since 1980s. Newer treatment modalities are emerging for neuroendocrine tumours (NETs) and chromaffin cell tumours (CCTs), but many of these do not yet have adequate long-term follow-up to determine their longer term efficacy and sequelae. Fifty-eight patients with metastatic NETs and CCTs who had received (131)I-MIBG therapy between 2000 and 2011 were analysed. Survival and any long-term haematological or renal sequelae were investigated. In the NET group, the overall median survival and median survival following the diagnosis of metastatic disease was 124 months. The median survival following the commencement of (131)I-MIBG was 66 months. For the CCT group, median survival had not been reached. The 5-year survival from diagnosis and following the diagnosis of metastatic disease was 67% and 67.5% for NETs and CCTs, respectively. The 5-year survival following the commencement of (131)I-MIBG therapy was 68%. Thirty-two patients had long-term haematological sequelae: 5 of these 32 patients developed haematological malignancies. Two patients developed a mild deterioration in renal function. Long follow up of (131)I-MIBG therapy reveals a noteable rate of bone marrow toxicities and malignancy and long term review of all patients receiving radionuclide therapies is recommended.

  11. 131I Metaiodobenzylguanidine (131I MIBG) kinetics in a carcinoid tumor

    International Nuclear Information System (INIS)

    Schiavo, R.; Concolino, G.; Fazi, F.; Iannantuono, P.; Voti, S. Li; Manzara, A.; Pavoni, P.

    1987-01-01

    The 131 I-MIBG kinetics was studied in vivo in patients with carcinoid tumors and liver metastases. Activity curve analysis showed that the maximum uptake of 131 I-MIBG in a carcinoid tumor occurred after 48 hours, while its biological half time was of 8 days and a half. Although more data are necessary to understand a significant variation in 131 I-MIBG kinetics between the different kinds of APUD neoplasms, it is thought that a dynamic-funtional study allowing the evaluation of the different biological half-time, could be helpful for the selection of these neoplasms, which could be treated with 131 I-MIBG. Radiation doses required for the treatment are also estimated. (M.E.L.) [es

  12. Malign pheochromocytoma: importance of the scintigraphic follow-up with metaiodobenzulguanidine 131I (MIBG-131I)

    International Nuclear Information System (INIS)

    Kato, M.; Velhote, V.V.; Souto, F.J.P.; Long, Y.J.; Costa, P.L.A.

    1989-01-01

    The authors report a case of pheochromocytoma investigated with metaiodobenzylguanidine labeled with 131 I (MIBG- 131 I). The methodology identify primitive lesion, its recurrence and metastasis. The authors mention the advantage of the technique due to the high specificity, sensitivity and because it is harmless, offering optimal information about the morphology and functional nature, concerning diagnosis and follow-up of the disease. (author) [pt

  13. Thyroid cancer following 131I therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Watanabe, Iwao

    1980-01-01

    A women aged 37 who had thyroid cancer after 131 I therapy for hyperthyroidism was reported. She had received various conservative therapies and surgical treatments for hyperthyroidism for 10 years before 131 I therapy. Similar cases were picked out from many reports, and their clinical characteristics were discussed. The incidence of thyroid cancer after 131 I therapy, age and sex of patients, dosage of 131 I, histological changes after the irradiation of 131 I, sites of thyroid cancer, and the relationship between 131 I therapy and the occurrence time of thyroid cancer were also considered. (Tsunoda, M.)

  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. "1"7"7Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer

    International Nuclear Information System (INIS)

    Braeuer, Axel; Grubert, Lena Sophie; Roll, Wolfgang; Schaefers, Michael; Rahbar, Kambiz; Schrader, Andres Jan; Boegemann, Martin

    2017-01-01

    Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with "1"7"7Lu-PSMA-617. Between December 2014 and January 2017, 59 consecutive patients (median age 72 years); interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study. Biochemical response was evaluated using Prostate Cancer Working Group 3 (PCWG3) criteria. Survival was evaluated using Kaplan-Meier estimates and Cox regression proportional hazards model. Toxicity was assessed using Common Toxicity Criteria for Adverse Events (CTCAE). The study was approved by the local ethics committee. The 59 patients were treated with a total of 159 cycles (median 3 cycles, range 1-7) of "1"7"7Lu-PSMA-617 (median dose 6.11 GBq, IQR 5.9-6.3 GBq). The median follow-up was 24 weeks (IQR 15-36 weeks). Follow-up data for at least 12 weeks (PCWG3) were available in 76% (45) of the patients. For outcome results data from all patients treated with at least one cycle were analysed. A decline in prostate-specific antigen (PSA) of ≥50% occurred in 53%, and a decline in PSA of any amount in 91% of patients. The estimated median OS was 32 weeks. An initial alkaline phosphatase (ALP) level <220 U/L and a PSA decline after the first cycle were associated with a longer OS (56 vs. 28 weeks, p < 0.01, and 56 vs. 29 weeks, p = 0.04, respectively). The median estimated PSA progression-free survival (PPFS) was 18 weeks. Only ALP level <220 U/L was significantly associated with a longer PPFS (41 vs. 18 weeks, p < 0.01). A PSA decline after the first cycle of "1"7"7Lu-PSMA-617 and an initial ALP level <220 U/L were predictors of a longer OS in patients with end-stage mCRPC. An ALP level <220 U/L was additionally associated with a longer PPFS. (orig.)

  16. Evaluation of 177Lu[Lu]-CHX-A″-DTPA-6A10 Fab as a radioimmunotherapy agent targeting carbonic anhydrase XII.

    Science.gov (United States)

    Fiedler, L; Kellner, M; Gosewisch, A; Oos, R; Böning, G; Lindner, S; Albert, N; Bartenstein, P; Reulen, H-J; Zeidler, R; Gildehaus, F J

    2018-05-01

    Due to their infiltrative growth behavior, gliomas have, even after surgical resection, a high recurrence tendency. The approach of intracavitary radioimmunotherapy (RIT) is aimed at inhibiting tumor re-growth by directly administering drugs into the resection cavity (RC). Direct application of the radioconjugate into the RC has the advantage of bypassing the blood-brain barrier, which allows the administration of higher radiation doses than systemic application. Carbonic anhydrase XII (CA XII) is highly expressed on glioma cells while being absent from normal brain and thus an attractive target molecule for RIT. We evaluated a CA XII-specific 6A10 Fab (fragment antigen binding) labelled with 177 Lu as an agent for RIT. 6A10 Fab fragment was modified and radiolabelled with 177 Lu and characterized by MALDI-TOF, flow cytometry and radio-TLC. In vitro stability was determined under physiological conditions. Biodistribution studies, autoradiography tumor examinations and planar scintigraphy imaging were performed on SCID-mice bearing human glioma xenografts. The in vitro CA XII binding capacity of the modified Fab was confirmed. Radiochemical purity was determined to be >90% after 72 h of incubation under physiological conditions. Autoradiography experiments proved the specific binding of the Fab to CA XII on tumor cells. Biodistribution studies revealed a tumor uptake of 3.0%ID/g after 6 h and no detectable brain uptake. The tumor-to-contralateral ratio of 10/1 was confirmed by quantitative planar scintigraphy. The radiochemical stability in combination with a successful in vivo tumor uptake shows the potential suitability for future RIT applications with the 6A10 Fab. Copyright © 2018 Elsevier Inc. All rights reserved.

  17. Development and validation of a simple model for cellular and cell cluster dosimetry with practical application in targeted radionuclide therapy

    International Nuclear Information System (INIS)

    Bardies, M.; Myers, M.J.

    1992-01-01

    The authors have developed an analytical technique for calculating the mean absorbed dose to the cell nucleus from a variety of spatial distributions of cells and activities and a wide range of emitted energies and radionuclides. The dose to the nucleus has been calculated using this method from activity distributed (1) on the cell surface (2) throughout the cytoplasm (3) throughout a cluster of cells (micrometastasis) and (4) on the surface of the cluster of cells. The derived absorption factors have been based on the latest point kernels of Berger and have been validated against published estimates. They show good agreement and the model has the advantage of being easily adapted for revisions and extensions of available low energy data. Data sets may be derived with the absorbed fractions or the absorbed dose per emission as a function of the radial extent of the activity, and either the individual energies of the emissions or the totality of the emissions from a particular radio-nuclide. The practical applications of the model have included: (a) calculation of the absorbed dose to radioimmuno-targeted micrometastasis in the peritoneum; (b) calculations of doses to cells labelled on the surface with some novel emitters such as 67 Cu, 177 Lu, 153 Sm, 111 Ag, 186 Re, 188 Re as well as 131 I, 125 I and 90 Y; (c) comparison of doses to the cell nucleus from MIBG labelled with 125 I and 131 I and distributed in the cytoplasm of the cell; and (d) estimates of the absorbed dose to the cell nucleus from alpha emitters distributed on the surface of the cell

  18. In vitro and in vivo studies in Balb-c and nude mice of a new {sup 177}Lu-Bombesin analog developed for prostate tumor diagnosis and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Pujatti, Priscilla B.; Santos, Josefina S.; Couto, Renata M.; Araujo, Elaine B. de; Mengatti, Jair [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia], e-mail: priscillapujatti@yahoo.com.br; Suzuki, Miriam F. [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Centro de Biotecnologia

    2009-07-01

    In this work we describe the radiolabeling with {sup 177}Lu and some properties of the novel bombesin analog BBNp6 - DOTA-X-BBN(6-14), where X is a spacer of six aminoacids. Bombesin (BBN) is an analog of human gastrin releasing peptide (GRP) isolated from the skin of the frog Bombina bombina in 1970. Development of radiolabeled BBN derivatives as agents for diagnostic imaging and systemic radiotherapy has increased considerable because of the observation that GRP receptors (GRPr) are over-expressed in a variety of human tumor cells, such as prostate tumor cells. {sup 177}Lu-labeled peptides are attractive due to the excellent radiophysical properties and commercial availability of the radiometal. BBNp6 was labeled with high yield after reacting with 92.5 MBq of {sup 177}LuCl3 at 90 deg C for 30 minutes and this mixture kept stable for more than 96 hours at 4 deg C and 1 hour in human plasma. In vivo studies showed a multicompartimental distribution model with fast blood clearance, mainly performed by renal pathway. In addition, {sup 177}Lu-BBNp6 showed high affinity for PC-3 tumor xenografts, but not for pancreas and intestine (GRP positive tissues), suggesting its specificity and usefulness for prostate tumor treatment. Moreover, scintigraphic images showed that this derivative can also be a tool in this tumor diagnosis. So, BBNp6 is a promising radiopharmaceutical for prostate tumor imaging and treatment. (author)

  19. Adrenal scintigraphy using 131I-Adosterol

    International Nuclear Information System (INIS)

    Fukunaga, Masao; Dokoh, Shigeharu; Yamamoto, Itsuo; Morita, Rikushi; Torizuka, Kanji

    1977-01-01

    131 I-Adosterol (6β-iodomethyl-19-norcholest-5(10)-3β-ol) was administered to evaluate adrenal grand in 20 patients including 9 patients with primary aldosteronism, 5 with Cushing's syndrome, one with pheochromocytoma, one with retroperitoneal tumor, 3 with essential hypertension and one with obesity. Standard scintigraphies were performed at 3rd day and again 6th day after administration of 131 I-adosterol (1-1.5 mCi). Suppression scintigraphies were obtained while the patients were taking dexamethasone 2 to 3 mg daily from 3 days prior to injection of the tracer until adrenal imaging. In the cases with essential hypertension and obesity, both adrenal glands were delineated equally by standard scintigraphy, and in one patient, undergone suppression scintigraphy, the uptake of 131 I-adosterol by both glands were completely inhibited by dexamethasone administration. In primary aldosteronism, six of the 9 patients demonstrated the increased radioactivity in one side, and were diagnosed as aldosteronoma. In 3 cases, failed to show the lesions on standard scintigraphy, the lesions could be detected by suppression scintigraphy, and aldosteronomas measuring 1 x 1 x 0.7, 2 x 2 x 1 and 1.7 x 1.5 x 0.8 cm were confirmed by operation. In Cushing's syndrome, standard scintigraphy could easily distinguish between adenoma (one case) and bilateral hyperplasia (4 cases). Adrenal scintigraphy was also a useful method in order to assess the effect of pituitary irradiation therapy in the case of hyperplasia. In pheochromocytoma and retroperitoneal tumor, the side of the lesion was identified by the absence of a functioning gland. Suppression scintigraphy was particularly useful in detecting the localization of the small tumor in primary aldosteronism. (auth.)

  20. Determination of inorganic radioiodine in 131I- Rose Bengal and 131I- bromosulphthalein

    International Nuclear Information System (INIS)

    Toledo e Souza, I.T. de; Pereira, N.P.S. de; Silva, C.P.G. da.

    1985-01-01

    A rapid miniaturized chromatographic system was developed for fast determination of the proportion of inorganic radioactive iodide from radiopharmaceuticals 131 I-Rose Bengal and 131 I-Bromosulphthalein. Using 33% W/V aqueous solution of ammonium sulphate pH 7,5 as a solvent Rf values for radiopharmaceuticals, iodide, iodate to Rf 0,0 0,5 0,9 respectively. The chromatographic quality control procedures are easy to use, rapid and can be incorporated in a routine quality control program. (Author) [pt

  1. Preparation of therapeutic dose of 177Lu-DOTA-TATE using a novel single vial freeze-dried kit: a comparison with 'in-situ' preparation at hospital radiopharmacy.

    Science.gov (United States)

    Das, Tapas; Banerjee, Sharmila; Shinto, Ajit; Kamaleshwaran, K K; Sarma, H D

    2014-01-01

    Patient dose of (177)Lu-DOTA-TATE, used for providing radiotherapeutic treatment to the patients suffering from cancers of neuroendocrine origin, could be prepared at the hospital radiopharmacy either 'in-situ' or by using freezedried kits. The objective of the present work is to formulate and evaluate a single vial freeze-dried DOTA-TATE kit, which is capable of producing up to 7.4 GBq (200 mCi) dose of (177)Lu-DOTA-TATE and to compare the two methodologies presently used for the preparation of the agent. Freeze-dried DOTA-TATE kits, comprising a lyophilized mixture of DOTA-TATE, gentisic acid and ammonium acetate, were prepared and used for the formulation of patient doses of (177)Lu-DOTA-TATE. The kits were subjected to detailed radiochemical evaluation and the shelf-life of the kits was determined. The pharmacokinetic behavior of the agent was studied in normal Wistar rats. These kits were utilized for treating the patients suffering from various types of neuroendocrine cancers. The freeze-dried kits were used for the preparation of up to 7.4 GBq (200 mCi) therapeutic doses of (177)Lu- DOTA-TATE with a radiochemical purity of >99% and were found to have sufficiently long shelf-life. Biological studies carried out in normal Wistar rats exhibited no significant accumulation of activity in any of the vital organs/tissue except in kidneys and non-accumulated activity showed major renal clearance. Clinical studies carried out in cancer patients exhibited accumulation of activity in the cancerous lesions and metastatic sites. The kit was useful for the convenient preparation of therapeutic dose of (177)Lu-DOTA-TATE, suitable for human administration. The use of kit is expected to reduce the batch failure and radiation exposure to the working personnel.

  2. Occupational exposure to 99mTc and 131I in a radiopharmacy room

    International Nuclear Information System (INIS)

    Valle, Bruna P.; Cunha, Kenya Dias da; Sa, Lidia Vasconcellos de; Souza, Wanderson; Santos, Maristela; Medeiras, Geiza; Conceicao, Cirilo S.

    2009-01-01

    Brazil has about 310 nuclear medicine services and 90% of these services use Molybdenum/Technetium generators to prepare several radiopharmaceuticals to diagnostics; about 70% use also 131 I for diagnosis and therapy. These radionuclides are associated to compounds in liquid form and during the manipulation to prepare and administer the patient dose some radioactive airborne particle can be generated. As consequence the workers can be exposed to airborne particles in the respirable fraction containing 99m Tc and 131 I. The aim of this study is develop a simple and rapid method to verify if the exhaust systems installed in the SMN are efficient in preventing the inhalation of radionuclides airborne particles by workers. In order to estimate the occupational exposure a nuclear medicine service was selected and aerosol samples were collected using personal air sampler with a cyclone. The samples were analyzed using a germanium detector system and the 99m Tc and 131 I average concentrations were obtained as 16,6 ± 14,34 mBq/m 3 and 0.72 ± 0.36 mBq/m 3 , respectively. It was not observed a correlation among air concentration and total activity processed in laboratory. These results show that the worker inhales airborne particles containing 99m Tc and 131 I. (author)

  3. Occupational exposure to {sup 99m}Tc and {sup 131}I in a radiopharmacy room

    Energy Technology Data Exchange (ETDEWEB)

    Valle, Bruna P.; Cunha, Kenya Dias da; Sa, Lidia Vasconcellos de; Souza, Wanderson; Santos, Maristela; Medeiras, Geiza; Conceicao, Cirilo S. [Universidade do Estado, Nova Friburgo, RJ (Brazil). Inst. Politecnico. Dept. de Modelagem Computacional], e-mail: brunapvalle@gmail.com, e-mail: kenya@ird.gov.br, e-mail: lidia@ird.gov.br, e-mail: wander@ird.gov.br, e-mail: mstela@ird.gov.br; Abrantes, Marcio Borges de [Centro de Medicina Nuclear Guanabara, Rio de Janeiro, RJ (Brazil)], e-mail: marcioabrantes@pop.com.br

    2009-07-01

    Brazil has about 310 nuclear medicine services and 90% of these services use Molybdenum/Technetium generators to prepare several radiopharmaceuticals to diagnostics; about 70% use also {sup 131}I for diagnosis and therapy. These radionuclides are associated to compounds in liquid form and during the manipulation to prepare and administer the patient dose some radioactive airborne particle can be generated. As consequence the workers can be exposed to airborne particles in the respirable fraction containing {sup 99m}Tc and {sup 131}I. The aim of this study is develop a simple and rapid method to verify if the exhaust systems installed in the SMN are efficient in preventing the inhalation of radionuclides airborne particles by workers. In order to estimate the occupational exposure a nuclear medicine service was selected and aerosol samples were collected using personal air sampler with a cyclone. The samples were analyzed using a germanium detector system and the {sup 99m}Tc and {sup 131}I average concentrations were obtained as 16,6 {+-} 14,34 mBq/m{sup 3} and 0.72 {+-} 0.36 mBq/m{sup 3}, respectively. It was not observed a correlation among air concentration and total activity processed in laboratory. These results show that the worker inhales airborne particles containing {sup 99m}Tc and {sup 131}I. (author)

  4. Production of 131I gelatin capsules

    International Nuclear Information System (INIS)

    Freud, A.; Hirshfeld, N.; Canfi, A.; Melamud, Y.

    1997-01-01

    Radioiodine ( 131 I) hard-gelatin capsules are widely used for the diagnosis and treatment of various thyroid disorders. Until 1980 radioiodine was supplied by us as a liquid dosage. This proved to be a rather inconvenient form since it resulted in inaccurate dosing by the physicians and caused frequent contamination of the patients and the hospital personnel. In an attempt to overcome these problems we have designed and constructed a production facility for capsules in which 1311 is packaged. Because of the extreme precautions necessary in handling radioactive compounds, encapsulation of radioactive materials requires specifically designed production techniques, special instrumentation and unique quality control procedures that are not encountered in the standard capsule production processes in the pharmaceutical industry

  5. A new anticancer agent--131I BGTP

    International Nuclear Information System (INIS)

    He Jiaheng; Jiang Shubin; Wang Guanquan

    2007-12-01

    A new anticancer precursor, di-peptide[p-Boc-Gly-Tyr-NH(CH 2 ) 2 NH-PO (ONH 4 )-O-PhI*], was synthesized and labelled with 131 I using enveloped-tube technique, the labelling yield could reach 85%. Using cell coalescent method, the biological activity in vitro of the labelled compounds was evaluated, showing that the primary appetency was kept and not damaged obviously during labelling. Results on judgement of their stability, lipophilicity and toxicity demonstrated lower toxicity, higher lipophilicity and lower iodium disassociation percentage (<12% after 72 h); furthermore, a tumour-bearing animal model, was establishd successfully, on which, the biological properties of the labelled agent was studied. (authors)

  6. Behavior of medically-derived 131I in the tidal Potomac River

    International Nuclear Information System (INIS)

    Rose, Paula S.; Smith, Joseph P.; Cochran, J. Kirk; Aller, Robert C.; Swanson, R. Lawrence

    2013-01-01

    Iodine-131 (t 1/2 = 8.04 d) is administered to patients for treatment of thyroid disorders, excreted by patients and discharged to surface waters via sewage effluent. Radionuclides generally behave like their stable analogs; therefore, medically-derived 131 I is useful as a transport-reaction tracer of anthropogenic inputs and the aquatic biogeochemistry of iodine. Iodine-131 was measured in Potomac River water and sediments in the vicinity of the Blue Plains Water Pollution Control Plant (WPCP), Washington, DC, USA. Concentrations measured in sewage effluent from Blue Plains WPCP and in the Potomac River suggest a relatively continuous source of this radionuclide. The range of 131 I concentrations detected in surface water was 0.076 ± 0.006 to 6.07 ± 0.07 Bq L −1 . Iodine-131 concentrations in sediments ranged from 1.3 ± 0.8 to 117 ± 2 Bq kg −1 dry weight. Partitioning in the sewage effluent from Blue Plains and in surface waters indicated that 131 I is associated with colloidal and particulate organic material. The behavior of medically-derived 131 I in the Potomac River is consistent with the nutrient-like behavior of natural iodine in aquatic environments. After discharge to the river via sewage effluent, it is incorporated into biogenic particulate material and deposited in sediments. Solid phase sediment profiles of 131 I indicated rapid mixing or sedimentation of particulate debris and diagenetic remineralization and recycling on short time scales. - Highlights: ► Medically-derived 131 I was measured in sewage effluent, river water, and sediments. ► Sediment 210 Pb and 7 Be profiles help characterize the sedimentary environment. ► 131 I flux to sediments in study area is ∼ 1% of that discharged in sewage effluent. ► 131 I distributions constrain reaction-transport processes to weekly time scales. ► Collectively these data are used to better understand iodine biogeochemistry

  7. The intratumoral distribution of radiolabeled 177Lu-BR96 monoclonal antibodies changes in relation to tumor histology over time in a syngeneic rat colon carcinoma model.

    Science.gov (United States)

    Örbom, Anders; Eriksson, Sophie E; Elgström, Erika; Ohlsson, Tomas; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik

    2013-08-01

    The therapeutic effect of radioimmunotherapy depends on the distribution of the absorbed dose in relation to viable cancer cells within the tumor, which in turn is a function of the activity distribution. The aim of this study was to investigate the distribution of (177)Lu-DOTA-BR96 monoclonal antibodies targeting the Lewis Y antigen over 7 d using a syngeneic rat model of colon carcinoma. Thirty-eight tumor-bearing rats were intravenously given 25 or 50 MBq of (177)Lu-DOTA-BR96 per kilogram of body weight and were sacrificed 2, 8, 24, 48, 72, 96, 120, or 168 h after injection, with activity measured in blood and tumor samples. Adjacent cryosections of each tumor were analyzed in 3 ways: imaging using a silicon-strip detector for digital autoradiography, staining for histologic characterization, or staining to determine the distribution of the antigen, vasculature, and proliferating cells using immunohistochemistry. Absorbed-dose rate distribution images at the moment of sacrifice were calculated using the activity distribution and a point-dose kernel. The correlations between antigen expression and both activity uptake and absorbed-dose rate were calculated for several regions of interest in each tumor. Nine additional animals with tumors were given unlabeled antibody to evaluate possible immunologic effects. At 2-8 h after injection, activity was found in the tumor margins; at 24 h, in viable antigen-expressing areas within the tumor; and at 48 h and later, increasingly in antigen-negative areas of granulation tissue. The correlation between antigen expression and both the mean activity and the absorbed-dose rate in regions of interest changed from positive to negative after 24 h after injection. Antigen-negative areas also increased over time in animals injected with unlabeled BR96, compared with untreated tumors. The results indicate that viable Lewis Y-expressing tumor cells are most efficiently treated during the initial uptake period. The activity then seems

  8. Behavior of Na131I and meta(131I) iodobenzylguanidine (MIBG) in municipal sewerage.

    Science.gov (United States)

    Fenner, F D; Martin, J E

    1997-08-01

    Behavior of 131I activity in primary sludge at the Ann Arbor, Michigan, Municipal Waste Water Treatment Plant was studied in relation to known radioiodine therapy events at the University of Michigan Hospital complex. The principal compounds administered are Na131I, which has widespread use, and meta (131I) iodobenzylguanidine (MIBG), which is a compound unique to the University of Michigan, although labeled antibodies and other forms are also used in therapy and research. The objectives of the study were to determine the environmental fate of such discharges and to determine radiation exposures to workers and the public when sludges are incinerated. Approximately 17% of the MIBG activity administered in a therapy was found in the primary sludge, whereas only 1.1% of the Na131I was in sludge. When land applied, the short half life of 131I in the sludge presents few radiological health concerns; however, incineration, which is done in winter months, is assumed to release organically bound 131I to the atmosphere. Radiation doses due to incineration of sludge containing measured concentrations were calculated for a maximally exposed worker to be 1.7 microSv (0.17 mrem) of which 0.48 microSv (0.048 mrem) was due to a 2-d upset condition. For a more typically exposed worker, and a member of the public, the committed effective dose equivalents were 1.2 microSv (0.12 mrem) and 0.06 microSv (0.006 mrem), respectively, for a 22-wk incineration period with release of all radioiodine in the sludge. Transport time to the treatment plant for radioiodine was found to be much longer than that of normal sewage, possibly due to organic material in sewer lines that absorb iodine. The residence time of radioiodine in the sewer also appears to be longer than expected; whether other radioactive materials are held up the same way is not known but chemical form is surely a factor.

  9. Preliminary study of 7Be, 137Cs and 131I activity concentration distribution rule in Beijing aerosol

    International Nuclear Information System (INIS)

    Fan Yuanqing; Wang Shilian; Zhang Xinjun; Li Qi; Jia Huaimao; Zhao Yungang; Chen Zhanying; Chang Yinzhong; Liu Shujiang; Li Huijuan

    2013-01-01

    The process of aerosol sampling and measuring of Beijing Radionuclide Station and Beijing Radionuclide Laboratory of the Comprehensive Nuclear-Test-Ban Treaty (CTBT) International Monitoring System (IMS) was described. Long time aerosol monitoring data of the station and the laboratory were analyzed through statistic method and the characteristic and rule of the concentration distribution of nuclides 7 Be, 137 Cs and 131 I were obtained. The foundation was formed for further studying the rule of the radionuclide distribution in atmosphere. (authors)

  10. Investigation of efficient {sup 131}I production from natural uranium at Tehran research reactor

    Energy Technology Data Exchange (ETDEWEB)

    Khalafi, H. [Nuclear Research Center, AEOI, No. 54 North Kargar Avenue, P.O. Box 14155/1339, Tehran (Iran, Islamic Republic of)]. E-mail: hossein_khalafi@yahoo.com; Nazari, K. [Jaber-Ibne-Hayan Research laboratories, AEOI, P.O. Box 11365/8486, Tehran (Iran, Islamic Republic of); Ghannadi-Maragheh, M. [Jaber-Ibne-Hayan Research laboratories, AEOI, P.O. Box 11365/8486, Tehran (Iran, Islamic Republic of)

    2005-05-15

    Iodine-131, which has a half-life of 8.05 days, is the one of the most widely used radionuclides in medical diagnosis and treats some diseases of thyroid gland. Optimization of {sup 131}I production in Tehran research reactor (TRR) was studied by two different methods. Primarily, standard nuclear codes such as ORIGEN, WIMS and CITATION were applied and then analytical solutions technique was followed. Calculated results and experimental works in the bench scale indicate that, by irradiation of 100 g natural Uranium (UO{sub 2}) for 100 h at 3.5 x 10{sup 13} (n's/cm{sup 2} s) thermal neutron flux in the TRR, one can produce about 5 Ci of {sup 131}I for medical purposes, on the other hand can produce very useful radionuclides like {sup 99}Mo and {sup 133}Xe in one batch irradiation in the unique production line.

  11. Investigation of efficient 131I production from natural uranium at Tehran research reactor

    International Nuclear Information System (INIS)

    Khalafi, H.; Nazari, K.; Ghannadi-Maragheh, M.

    2005-01-01

    Iodine-131, which has a half-life of 8.05 days, is the one of the most widely used radionuclides in medical diagnosis and treats some diseases of thyroid gland. Optimization of 131 I production in Tehran research reactor (TRR) was studied by two different methods. Primarily, standard nuclear codes such as ORIGEN, WIMS and CITATION were applied and then analytical solutions technique was followed. Calculated results and experimental works in the bench scale indicate that, by irradiation of 100 g natural Uranium (UO 2 ) for 100 h at 3.5 x 10 13 (n's/cm 2 s) thermal neutron flux in the TRR, one can produce about 5 Ci of 131 I for medical purposes, on the other hand can produce very useful radionuclides like 99 Mo and 133 Xe in one batch irradiation in the unique production line

  12. /sup 131/I-Bromsulphalein in the evaluation of hepatic function during reconvalescence after viral hepatitis

    Energy Technology Data Exchange (ETDEWEB)

    Chernysheva, N N; Pal' tseva, T F; Nonikova, T B; Aleshkovich, T V; Kuandykova, S Zh; Rumyantseva, L A; Kal' nitskaya, E F [Tsentral' nyj Inst. Usovershenstvovaniya Vrachej, Moscow (USSR)

    1982-10-01

    The combined use of biochemical and radionuclide tests (the clearance of /sup 131/I-bromsulphalein) made it possible to reveal significant differences in 53 patients in the time of complete reparation of hepatic function and the period of reconvalescence after hepatitis A and B. The period of reconvalescence in patients with hepatitis B was more prolonged. Dynamic observation and appropriate treatment is recommended for these patients.

  13. Standardization of 131I therapy for Graves disease

    International Nuclear Information System (INIS)

    Tang Jianlin; Li Yuying; Gao Liuyan; Tang Xiuping; Hu Hongyong

    2011-01-01

    Objective: To establish the normative and standard measures, to ensure medical safety and quality of care of the patients with Graves disease treated by 131 I therapy. Methods: Formulating and strictly implementing the medical organizational and technical measures of 131 I therapy for Graves disease and regular follow-up. Results: Receiving 131 I treatment of 104 patients, follow-up 6-36 months, no adverse events, the cure rate of 59.6%, the efficient rate is 99.9%. Conclusion: It is important guarantee for the medical quality and safety to standardize the 131 I therapy of Graves disease. (authors)

  14. Analysis of 131I therapy in 71 patients with hyperthyroidism

    International Nuclear Information System (INIS)

    Wang Ping; Chen Zequan; Wang Yuanzhi; Ye Shiqing

    2001-01-01

    Objective: To evaluate the clinical significance of iodine-131 treatment in patients with hyperthyroidism. Methods: The dose of 131 I was determined according to thyroid absorption of 131 I at 24 hrs post administration and thyroid weight estimated in ECT examination. Results: One dose cure rate of 131 I treatment was 96% (68/71). Hypothyroidism occurred in 3 of 71 patients (4%) in one year after administration. No other serious complication was observed. Conclusion: The therapeutic effect of 131 I in treating hyperthyroidism was quite encouraging. The administration regime was also simple

  15. 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

  16. Treatment of hyperthyroidism with /sup 131/I

    Energy Technology Data Exchange (ETDEWEB)

    Nakamura, I [Kumamoto Univ. (Japan); Tsuchikame, N; Katayama, K

    1980-05-01

    /sup 131/I therapy for hyperthyroidism is limited to those over middle age, women who do not want to bear a child, those in whom drugs are ineffective, those who relapse after operation, and those with severe complications. As to young patients, this therapy is limited to those in whom drugs of operation is ineffective. Basic line of absorbed doses is 5,000 rad. As to histological and immunological changes in the thyroid gland after this therapy, a relationship between pathogenesis of hypothyroidism and immunological mechanism must be discussed in future. The recovery rate of hyperthyroidism by this therapy was high (60 - 95%). The reported incidences of hypothyroidism after this therapy for 10 years were 12%, 15%, 29% and 67%. The maximum fault in this therapy is to induce hypothyroidism. Though the incidences of thyroid cancer, leukemia, and malformation after this therapy are not different from their spontaneous occurrence rates, clinical cases must be followed and observed strictly in future. Excepting this therapy, antithyroid drugs and operation are effective for this disease. Therefore, the therapy which is the most advantageous for the patients must be performed.

  17. Internal dosimetry of nuclear medicine workers through the analysis of 131I in aerosols

    International Nuclear Information System (INIS)

    Gomes C, L.; Lucena, E. A.; Da Silva S, C.; Almeida D, A. L.; Oliveira S, W.; Souza S, M.; Maranhao D, B.

    2014-08-01

    131 I is widely used in nuclear medicine for diagnostic and therapy of thyroid diseases. Depending of workplace safety conditions, routine handling of this radionuclide may result in a significant risk of exposure of the workers subject to chronic intake by inhalation of aerosols. A previous study including in vivo and in vitro measurements performed recently among nuclear medicine personnel in Brazil showed the occurrence of 131 I incorporation by workers involved in the handling of solutions used for radioiodine therapy. The present work describes the development, optimization and application of a methodology to collect and analyze aerosol samples aiming to assess internal doses based on the activity of 131 I present in a radiopharmacy laboratory. Portable samplers were positioned at one meter distant from the place where non-sealed liquid sources of 131 I are handled. Samples were collected over one hour using high-efficiency filters containing activated carbon and analyzed by gamma spectrometry with a high purity germanium detection system. Results have shown that, although a fume hood is available in the laboratory, 131 I in the form of vapor was detected in the workplace. The average activity concentration was found to be of 7.4 Bq /m 3 . This value is about three orders of magnitude below the Derived Air Concentration (Dac) of 8.4 kBq/m 3 . Assuming that the worker is exposed by inhalation of iodine vapor during one hour, 131 I concentration detected corresponds to an intake of 3.6 Bq which results in a committed effective dose of 7.13 x 10 -5 mSv. These results show that the radiopharmacy laboratory evaluated is safe in terms of internal exposure of the workers. However it is recommended that the presence of 131 I should be periodically re-assessed since it may increase individual effective doses. It should also be pointed out that the results obtained so far reflect a survey carried out in a specific workplace. Thus, it is suggested to apply the

  18. Dose-specific transcriptional responses in thyroid tissue in mice after 131I administration

    International Nuclear Information System (INIS)

    Rudqvist, Nils; Schüler, Emil; Parris, Toshima Z.; Langen, Britta; Helou, Khalil; Forssell-Aronsson, Eva

    2015-01-01

    , intermediate, and high absorbed doses from 131 I exposure in vivo. Using this approach, we have identified novel biological responses and potential absorbed dose-related biomarkers to 131 I exposure. Our research shows the importance of embracing technological advances and multi-disciplinary collaboration in order to apply them in radiation therapy, nuclear medicine, and radiation biology. Implications on Patient Care: This work may contribute with new knowledge of potential normal tissue effects or complications that may occur after exposure to ionizing radiation in diagnostic and therapeutic nuclear medicine, and due to radioactive fallout or accident with radionuclide spread

  19. Internal dosimetry of nuclear medicine workers through the analysis of {sup 131}I in aerosols

    Energy Technology Data Exchange (ETDEWEB)

    Gomes C, L.; Lucena, E. A.; Da Silva S, C.; Almeida D, A. L.; Oliveira S, W.; Souza S, M.; Maranhao D, B., E-mail: carneiro@ird.gov.br [Instituto de Radioprotecao e Dosimetria - CNEN, Av. Salvador Allende s/n, 22783-127 Rio de Janeiro (Brazil)

    2014-08-15

    {sup 131}I is widely used in nuclear medicine for diagnostic and therapy of thyroid diseases. Depending of workplace safety conditions, routine handling of this radionuclide may result in a significant risk of exposure of the workers subject to chronic intake by inhalation of aerosols. A previous study including in vivo and in vitro measurements performed recently among nuclear medicine personnel in Brazil showed the occurrence of {sup 131}I incorporation by workers involved in the handling of solutions used for radioiodine therapy. The present work describes the development, optimization and application of a methodology to collect and analyze aerosol samples aiming to assess internal doses based on the activity of {sup 131}I present in a radiopharmacy laboratory. Portable samplers were positioned at one meter distant from the place where non-sealed liquid sources of {sup 131}I are handled. Samples were collected over one hour using high-efficiency filters containing activated carbon and analyzed by gamma spectrometry with a high purity germanium detection system. Results have shown that, although a fume hood is available in the laboratory, {sup 131}I in the form of vapor was detected in the workplace. The average activity concentration was found to be of 7.4 Bq /m{sup 3}. This value is about three orders of magnitude below the Derived Air Concentration (Dac) of 8.4 kBq/m{sup 3}. Assuming that the worker is exposed by inhalation of iodine vapor during one hour, {sup 131}I concentration detected corresponds to an intake of 3.6 Bq which results in a committed effective dose of 7.13 x 10{sup -5} mSv. These results show that the radiopharmacy laboratory evaluated is safe in terms of internal exposure of the workers. However it is recommended that the presence of {sup 131}I should be periodically re-assessed since it may increase individual effective doses. It should also be pointed out that the results obtained so far reflect a survey carried out in a specific

  20. Cohort study of somatostatin-based radiopeptide therapy with [(90)Y-DOTA]-TOC versus [(90)Y-DOTA]-TOC plus [(177)Lu-DOTA]-TOC in neuroendocrine cancers.

    Science.gov (United States)

    Villard, Linda; Romer, Anna; Marincek, Nicolas; Brunner, Philippe; Koller, Michael T; Schindler, Christian; Ng, Quinn K T; Mäcke, Helmut R; Müller-Brand, Jan; Rochlitz, Christoph; Briel, Matthias; Walter, Martin A

    2012-04-01

    Radiopeptide therapy is commonly performed with a single radioisotope. We aimed to compare the effectiveness of somatostatin-based radiopeptide therapy with a single versus a combination of radioisotopes. In a cohort study, patients with metastasized neuroendocrine cancer were treated with repeated cycles of (90)yttrium-labeled tetraazacyclododecane-tetraacetic acid modified Tyr-octreotide ([(90)Y-DOTA]-TOC) or with cycles alternating between [(90)Y-DOTA]-TOC and (177)lutetium-labeled DOTA-TOC ([(177)Lu-DOTA]-TOC) until tumor progression or permanent toxicity. Multivariable Cox regression and competing risk regression were used to study predictors of survival and renal toxicity in patients completing three or more treatment cycles. A total of 486 patients completed three or more treatment cycles; 237 patients received [(90)Y-DOTA]-TOC and 249 patients received [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC. Patients receiving [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC had a significantly longer survival than patients receiving [(90)Y-DOTA]-TOC alone (5.51 v 3.96 years; hazard ratio, 0.64; 95% CI, 0.47 to 0.88; P = .006). The rates of severe hematologic toxicities (6.3% v 4.4%; P = .25) and severe renal toxicity (8.9% v 11.2%; P = .47) were comparable in both groups. [(90)Y-DOTA]-TOC + [(177)Lu-DOTA]-TOC was associated with improved overall survival compared with [(90)Y-DOTA]-TOC alone in patients completing three or more cycles of treatment. Contrary to the current practice in radiopeptide therapy, our results suggest an advantage of using a combination of radioisotopes.

  1. Developing historical food production and consumption data for 131I dose estimates: The Hanford experience

    International Nuclear Information System (INIS)

    Anderson, D.M.; Marsh, T.L.; Deonigi, D.A.

    1996-01-01

    This paper describes the methods used to reconstruct the movement of commercial foods in and through the study area of the Hanford Environmental Dose Reconstruction Project. The most dose-relevant radionuclide released from Hanford separations plants was 131 I via the atmospheric pathway. As a result of atmospheric deposition of 131 I, commercial food supplies may have been contaminated. Because of the half-life of 131 I is relatively short, foods consumed soon after production, such as milk and produce, presented the highest risk. For that reason, this paper deals primarily with the reconstruction of milk and produce production, marketing, and consumption from 1945-1951, the period with the highest known 131 I releases. The reconstructed food production and consumption information was used as input to radiation dose estimates for representative individuals and as default values for real individuals who may not remember where they obtained food or how much they consumed during that period. Specific methods for tracing the movement of commercial milk and produce back from the point of human consumption, through commercial markets, to original production are presented. Results include the characteristics of food consumption exhibited by representative individuals, examples of commercial milk and produce market structures, and a review of commercial milk production and processing practices from 1945-1951

  2. Renal 131I-hippuran extraction in man

    DEFF Research Database (Denmark)

    Hutchings, M; Hesse, B; Grønvall, J

    2002-01-01

    This study examined the 131I-hippuran extraction fraction during baseline renal blood flow rates and at high flow rates induced by dopamine.......This study examined the 131I-hippuran extraction fraction during baseline renal blood flow rates and at high flow rates induced by dopamine....

  3. 131I-BSP liver function test by BSP tolerance

    International Nuclear Information System (INIS)

    Kanda, Koichi

    1974-01-01

    131 I-BSP liver function test after BSP intravenous tolerance was discussed, assuming that the reason why measurements of 131 I-BSP retention rate at 30 minutes and 131 I-BSP disappearance rate in blood showed respectable overlapping between normal group and group with slight liver disorders as compared with BSP test and the reason why differential diagnosis was difficult were due to underestimate of tolerance volume of 131 I-BSP. 131 I-BSP was observed with time as to 70 persons with normal liver function and 257 cases of liver diseases, using 5, 3 and 2 mg of non-radioactive BSP tolerance volume per kilogram of body weight. 131 I-BSP retention rate at 30 minutes and 131 I-BSP disappearance rate in blood are possible to separate overlapping over control in each measurement value at 3-5 mg/kg of tolerance, and in comparison of 3 mg and 5 mg, the latter showed a little excellent result. So, it was decided that tolerance of 3 mg/kg was a proper dose, considering tolerance to liver cells. 131 I-BSP retention rate at 30 minutes was a little excellent in accuracy and disappearance rate in blood after BSP tolerance is simple and profitable for practical use because collection of blood was only one time and measurement could be made with whole blood. As mentioned above, this method is seemed to be useful to practice of liver function test. (Kanao, N.)

  4. Chemical and physical quality control of the HIPPURAN-131I

    International Nuclear Information System (INIS)

    Morin Zorilla, J.; Olive, E.; Isaac, M.; Cruz, J.

    1989-01-01

    Some physico-chemical methods for analytical control of Hippuran- 131 I are compared. The most convenient to applicate in hospitals and in more specialized quality control laboratories are recommended. The quality of Hippuran- 131 I produced by ISOTOP (USSR) is also evaluated. The product met the requirement of the International Pharmacopeia

  5. 131I therapy of Graves' disease using lithium

    International Nuclear Information System (INIS)

    Sato, Kenshi

    1983-01-01

    Lithium is known to cause goiter and hypothyroidism. In the mechanism of goitrogenesis, there is general agreement that lithium inhibits the release of the thyroid hormones from the thyroid gland without significantly impairing other thyroid functions. The present study was undertaken, therefore, to investigate the usefulness of lithium in the radioiodine treatment of Graves' disease. Nine patients with Graves' disease who were all, except one, previously treated with antithyroid drugs were studied. 600 mg of lithium carbonate were administered daily to investigate the effects on thyroidal 131 I uptake, disappearance rate of 131 I from the prelabeled thyroid and the serum concentrations of thyroid hormones. Lithium showed no significant effect on the thyroidal 131 I uptake when the 24 hour thyroidal 131 I uptakes were determined both before and during lithium treatment in the five cases. On the other hand, lithium clearly prolonged the mean value of effective half-lives of 131 I to approximately 8 days vs. 5.1 days before lithium treatment (p 4 and T 3 levels significantly decreased during lithium treatment, from 21.3 to 12.4μg/dl (n=9, p 131 I for the Graves' disease can be reduced by using lithium, the radiation exposure to the total body is decreased. Moreover, it is possible to perform the 131 I therapy while improving the thyrotoxicosis with lithium. Finally, it is concluded that lithium is a very useful drug to be combined with the 131 I therapy of Graves' disease. (author)

  6. The determination and monitoring of 131I activity in sewage treatment plants based on A2/O processes

    International Nuclear Information System (INIS)

    Jimenez, Fernando; Lopez, Raul; Pardo, Rafael; Deban, Luis; Garcia-Talavera, Marta

    2011-01-01

    131 I, a radionuclide used in nuclear medicine facilities, is habitually dumped into domestic sewer systems, which causes its control in municipal sewage treatment plants (STP) to become necessary. In this paper, we describe a procedure for the determination of the 131 I activity based on its precipitation as silver (I) iodide, its dissolution with cyanide in ammonia medium and its measurement by the liquid scintillation counting technique (LSC). After optimization, this LSC procedure allows the determination of 131 I activities with a limit of detection (CCβ) of 11 mBq kg -1 . The procedure was successfully validated by comparison with the normative and requires both less sample volume and measurement time than the standard procedure. The method has been applied to the monitoring of 131 I in the STP of Valladolid (Spain), which found activities below the maximum allowed by legislation and showed a near constant background 131 I activity in the influents with punctual increases corresponding to authorized spills. The mean 131 I removing efficiency of the STP was 52%.

  7. Response of monitors of surface contamination to internal exposition control from 131I in the 'nuclear medicine services'

    International Nuclear Information System (INIS)

    Puerta, Nancy; Rojo, Ana M.; Villella, Adrian; Gossio, Sebastian; Parada, Ines Gomez; Acosta, Norma; Arenas, German

    2013-01-01

    The IAEA, in its publication RS-G-1.2, proposes individual control of workers occupationally exposed with risk of internal exposure when the potential exposure provided by incorporation leads to a value of annual committed effective dose equal to or greater than 1 mSv. Because the radionuclide 131 I is the most important to control internal exposure in Nuclear Medicine Services, it is evaluated if the surface contamination monitors, commonly used in nuclear medicine centers of Argentina, would implement individual control of internal exposure to 131 I. Selected detectors were calibrated with a dummy neck and thyroid with calibrated sources of 131 I and 133 Ba reference. For each detector is was estimated the detection efficiency for 131 I and its detection limit. Each instrument was evaluated for the lowest effective dose possible to detect compromised by individual routine monitoring with different measurement intervals . We analyzed the response of each team for determining conditions that may be effective for the control of internal exposure of 131 I. Finally , we conclude that the daily individual monitoring surface contamination detectors available in the Nuclear Medicine Services is feasible to implement and ensures detection of significant additions of 131 I

  8. [sup 131]I-metaiodobenzylguanidine therapy for malignant pheochromocytoma

    Energy Technology Data Exchange (ETDEWEB)

    Sakahara, Harumi; Saga, Tsuneo; Hosono, Makoto; Kobayashi, Hisataka; Konishi, Junji (Kyoto Univ. (Japan). Faculty of Medicine); Endo, Keigo

    1994-05-01

    [sup 131]I-metaiodobenzylguanidine (MIBG) therapy was given to five patients with malignant pheochromocytoma. The patients received 1-3 doses of 3.33-4.625 GBq (total dose: 3.7 to 10.73 GBq). Partial tumor regression was observed in two patients, the tumor was unchanged in two patients, and slow progression was noted in one patient. Marked improvement in clinical symptoms was achieved in four patients. The other patients had no symptoms before [sup 131]I-MIBG treatment, but the serum epinephrine and dopamine decreased. There were no severe untoward responses in four patients. However, one patient developed transient but severe orthostatic hypotension, hypertension, and hyperglycemia from 1 week to 1 month after [sup 131]I-MIBG administration. Although complete remission was not obtained, all the patients achieved some benefit from [sup 131]I-MIBG therapy. Thus, [sup 131]I-MIBG appears to be useful for the palliation of malignant pheochromocytoma. (author).

  9. Use of the GEANT4 Monte Carlo to determine three-dimensional dose factors for radionuclide dosimetry

    Energy Technology Data Exchange (ETDEWEB)

    Amato, Ernesto, E-mail: eamato@unime.it [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences (Italy); Italiano, Antonio [INFN – Istituto Nazionale di Fisica Nucleare, Gruppo Collegato di Messina (Italy); Minutoli, Fabio; Baldari, Sergio [University of Messina, Department of Biomedical Sciences and of Morphologic and Functional Imaging, Section of Radiological Sciences (Italy)

    2013-04-21

    The voxel-level dosimetry is the most simple and common approach to internal dosimetry of nonuniform distributions of activity within the human body. Aim of this work was to obtain the dose “S” factors (mGy/MBqs) at the voxel level for eight beta and beta–gamma emitting radionuclides commonly used in nuclear medicine diagnostic and therapeutic procedures. We developed a Monte Carlo simulation in GEANT4 of a region of soft tissue as defined by the ICRP, divided into 11×11×11 cubic voxels, 3 mm in side. The simulation used the parameterizations of the electromagnetic interaction optimized for low energy (EEDL, EPDL). The decay of each radionuclide ({sup 32}P, {sup 90}Y, {sup 99m}Tc, {sup 177}Lu, {sup 131}I, {sup 153}Sm, {sup 186}Re, {sup 188}Re) were simulated homogeneously distributed within the central voxel (0,0,0), and the energy deposited in the surrounding voxels was mediated on the 8 octants of the three dimensional space, for reasons of symmetry. The results obtained were compared with those available in the literature. While the iodine deviations remain within 16%, for phosphorus, a pure beta emitter, the agreement is very good for self-dose (0,0,0) and good for the dose to first neighbors, while differences are observed ranging from −60% to +100% for voxels far distant from the source. The existence of significant differences in the percentage calculation of the voxel S factors, especially for pure beta emitters such as {sup 32}P or {sup 90}Y, has already been highlighted by other authors. These data can usefully extend the dosimetric approach based on the voxel to other radionuclides not covered in the available literature.

  10. Use of the GEANT4 Monte Carlo to determine three-dimensional dose factors for radionuclide dosimetry

    International Nuclear Information System (INIS)

    Amato, Ernesto; Italiano, Antonio; Minutoli, Fabio; Baldari, Sergio

    2013-01-01

    The voxel-level dosimetry is the most simple and common approach to internal dosimetry of nonuniform distributions of activity within the human body. Aim of this work was to obtain the dose “S” factors (mGy/MBqs) at the voxel level for eight beta and beta–gamma emitting radionuclides commonly used in nuclear medicine diagnostic and therapeutic procedures. We developed a Monte Carlo simulation in GEANT4 of a region of soft tissue as defined by the ICRP, divided into 11×11×11 cubic voxels, 3 mm in side. The simulation used the parameterizations of the electromagnetic interaction optimized for low energy (EEDL, EPDL). The decay of each radionuclide ( 32 P, 90 Y, 99m Tc, 177 Lu, 131 I, 153 Sm, 186 Re, 188 Re) were simulated homogeneously distributed within the central voxel (0,0,0), and the energy deposited in the surrounding voxels was mediated on the 8 octants of the three dimensional space, for reasons of symmetry. The results obtained were compared with those available in the literature. While the iodine deviations remain within 16%, for phosphorus, a pure beta emitter, the agreement is very good for self-dose (0,0,0) and good for the dose to first neighbors, while differences are observed ranging from −60% to +100% for voxels far distant from the source. The existence of significant differences in the percentage calculation of the voxel S factors, especially for pure beta emitters such as 32 P or 90 Y, has already been highlighted by other authors. These data can usefully extend the dosimetric approach based on the voxel to other radionuclides not covered in the available literature

  11. The {sup 68}Ga/{sup 177}Lu theragnostic concept in PSMA targeting of castration-resistant prostate cancer: correlation of SUV{sub max} values and absorbed dose estimates

    Energy Technology Data Exchange (ETDEWEB)

    Scarpa, Lorenza; Buxbaum, Sabine; Kendler, Dorota; Decristoforo, Clemens; Uprimny, Christian; Virgolini, Irene [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Fink, Katharina [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Medical University of Innsbruck, Department of Radiotherapy / Radiation Oncology, Innsbruck (Austria); Bektic, Jasmin; Horninger, Wolfgang [Medical University of Innsbruck, Department of Urology, Innsbruck (Austria); Gruber, Leonhard [Medical University of Innsbruck, Department of Radiology, Innsbruck (Austria); Lukas, Peter [Medical University of Innsbruck, Department of Radiotherapy / Radiation Oncology, Innsbruck (Austria)

    2017-05-15

    A targeted theragnostic approach based on increased expression of prostate-specific membrane antigen (PSMA) on PC cells is an attractive treatment option for patients with metastatic castration-resistant prostate cancer (mCRPC). Ten consecutive mCRPC patients were selected for {sup 177}Lu-PSMA617 therapy on the basis of PSMA-targeted {sup 68}Ga-PSMA-HBED-CC PET/CT diagnosis showing extensive and progressive tumour load. Following dosimetry along with the first therapy cycle restaging ({sup 68}Ga-PSMA-HBED-CC and {sup 18}F-NaF PET/CT) was performed after 2 and 3 therapy cycles (each 6.1 ± 0.3 GBq, range 5.4-6.5 GBq) given intravenously over 30 minutes, 9 ± 1 weeks apart. PET/CT scans were compared to {sup 177}Lu-PSMA617 24-hour whole-body scans and contrast-enhanced dual-phase CT. Detailed comparison of SUVmax values and absorbed tumour doses was performed. {sup 177}Lu-PSMA617 dosimetry indicated high tumour doses for skeletal (3.4 ± 1.9 Gy/GBq; range 1.1-7.2 Gy/GBq), lymph node (2.6 ± 0.4 Gy/GBq; range 2.3-2.9 Gy/GBq) as well as liver (2.4 ± 0.8 Gy/GBq; range 1.7-3.3 Gy/GBq) metastases whereas the dose for tissues/organs was acceptable in all patients for an intention-to-treat activity of 18 ± 0.3 GBq. Three patients showed partial remission, three mixed response, one stable and three progressive disease. Decreased {sup 177}Lu-PSMA617 and {sup 68}Ga-PSMA-HBED-CC uptake (mean SUVmax values 20.2 before and 15.0 after 2 cycles and 11.5 after 3 cycles, p < 0.05) was found in 41/54 skeletal lesions, 12/13 lymph node metastases, 3/5 visceral metastases and 4/4 primary PC lesions. Due to substantial individual variance, dosimetry is mandatory for a patient-specific approach following {sup 177}Lu-PSMA617 therapy. Higher activities and/or shorter treatment intervals should be applied in a larger prospective study. (orig.)

  12. 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.

  13. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [{sup 177}Lu]Lu-PSMA-617

    Energy Technology Data Exchange (ETDEWEB)

    Ahmadzadehfar, Hojjat; Wegen, Simone; Yordanova, Anna; Kuerpig, Stefan; Eppard, Elisabeth; Wei, Xiao; Schlenkhoff, Carl; Essler, Markus [University Hospital Bonn, Department of Nuclear Medicine, Bonn (Germany); Fimmers, Rolf [University of Bonn, Institute for Medical Biometry, Informatics and Epidemiology, Bonn (Germany); Hauser, Stefan [University Hospital Bonn, Department of Urology, Bonn (Germany)

    2017-08-15

    Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [{sup 177}Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles. (orig.)

  14. 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)

    Kashyap, Raghava; Eu, Peter; Jackson, Price; Hofman, Michael S.; Hicks, Rodney J.; Beauregard, Jean-Mathieu; Zannino, Diana

    2013-01-01

    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 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.)

  15. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [177Lu]Lu-PSMA-617.

    Science.gov (United States)

    Ahmadzadehfar, Hojjat; Wegen, Simone; Yordanova, Anna; Fimmers, Rolf; Kürpig, Stefan; Eppard, Elisabeth; Wei, Xiao; Schlenkhoff, Carl; Hauser, Stefan; Essler, Markus

    2017-08-01

    Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [ 177 Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle. The tumour marker prostate-specific antigen (PSA) was used as the marker for response evaluation. Fifty-two patients underwent a total of 190 cycles of RLT (3-6 cycles per patient). Of these, 80.8% showed a decline in PSA 2 months after the first cycle, with 44.2% showing a PSA decline of ≥50%. When compared to baseline PSA, 73.1% showed a PSA decline after the third cycle. 50% of patients that did not show any response to the first cycle also did not respond to the second and third cycles. The median OS was 60 weeks in all patients. The median OS was significantly longer for patients that showed any PSA decline after the first cycle compared to patients without PSA decline (68 vs. 33 weeks). There was a significant difference in median OS between responders and non-responders for a change in PSA after the third cycle compared to baseline PSA. Patients with a positive response to RLT, regardless of the rate of decline, had a significantly longer median OS. Of the patients that did not show any response to the first cycle, 50% responded to the second or third cycles.

  16. 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.)

  17. Equipment and obtention process of 131I by dry distillation starting from TeO2

    International Nuclear Information System (INIS)

    Alanis M, J.

    2000-08-01

    The present invention refers to an equipment and process for the obtaining of 131 I by dry distillation starting from TeO 2 that has three interconnected systems, the manipulation system, the electric system and the distillation system, the combination of these systems, allows to improve the yield and the separation of the 131 I during the distillation process, since inside the electric system it is an oven that has a special design based on a temperature gradient. The more relevant aspects of the equipment its are the design of each one of its components that give as result the effectiveness of the production of 131 I in routinary form (industrial) whose final product can end up reaching a radiochemical purity up to 99% and a radionuclide purity of approximately 100%. The object of this invention is to provide a distillation equipment different to those that at the moment exist, thanks to its novel internal construction whose main characteristics already gather advantages on those existent. The reaction of obtaining of the TeO 2 , the development of the technique and studies of TeO 2 sintering and the irradiation experiments, its contributed to characterize with more precision the 'new process of obtaining of 131 I by dry via starting from the Te' developed in the ININ, and in this way it was achieved a more pure product, more economic, with less risks, from a point of view of Radiological Safety and mainly that it avoids the import to the country and it makes to self-sufficient Mexico in the production of 131 I. (Author)

  18. 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)

    Zhang, Hanwen; Maecke, Helmut R.; Schuhmacher, Jochen; Eisenhut, Michael; Waser, Beatrice; Reubi, Jean Claude; Wild, Damian

    2007-01-01

    We aimed at designing and developing a novel bombesin analogue, DOTA-PEG 4 -BN(7-14) (DOTA-PESIN), with the goal of labelling it with 67/68 Ga and 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 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 III /Lu III ]-DOTA-PESIN showed good affinity to GRP and neuromedin B receptors but no affinity to BB3. [ 67 Ga/ 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 [ 67 Ga/ 177 Lu]-DOTA-PESIN. [ 67 Ga/ 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 [ 68 Ga]-DOTA-PESIN was successful in visualising the tumour at 1 h post injection. Planar scintigraphic imaging showed that the 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 68/67 Ga and targeted radionuclide therapy with 177 Lu. (orig.)

  19. Quality control of 131I treatment of graves' disease

    International Nuclear Information System (INIS)

    Liu Zeng; Liu Guoqiang

    2009-01-01

    To make a preliminary quality control (QC) criteria and apply on the various stages of clinic 131 I treatment of Graves' disease in order to decrease the early happening of hypothyroidism and enhance the onetime 131 I cure rate of Graves' disease, the quality control criteria in the stochastic outpatient with 131 I treatment, such as plan of the indication, contraindication, method of treatment, matters needing attention, follow-up observation and curative effect appraisal, patient selection, RAIU, thyroid gland weight measurement and 131 I dose criteria for the various steps of 131 I medication were determined. The 131 I treatment effects of Graves' disease including the once-cure rate, the improving rate, duplicate cure rate and the early happening rate of hypothyroidism were analyzed in patients with applying QC and without QC ccriteria. The results showed that the oncecure rate in patients with applying QC criteria was increased from 76.6% to 90.9% (P≤0.01); the improving rate was decreased from 12.2% to 7.0% (P≤0.01); the duplicate cure rate was increased from 90.1% to 93.0% (P>0.05); the early happening rate of hypothyroidism was decreased from 11.0% to 2.1% (P≤0.01). The 131 I treatment of Graves' disease applying with QC criteria had tremendously improved the oncecure rate and decreased the early happening of hypothyroidism rate. (authors)

  20. Effect of 131I therapy on outcomes of Graves' ophthalmopathy

    International Nuclear Information System (INIS)

    Wang Renfei; Tan Jian; Zhang Guizhi; Yin Liang

    2011-01-01

    Objective: To analyze the correlation between the therapeutic effect of Graves' hyperthyroidism and the outcomes of Graves' ophthalmopathy after 131 I therapy, and to explore the effect of 131 I treatment on turnout of Graves' ophthalmopathy. Methods: Six hundreds and fifty-two patients of Graves' disease accompanied with Graves' ophthalmopathy, received one-time 131 I treatment according to routine procedure. We recorded exophthalmometer readings, the signs and symptoms of eyes before therapy. Regular follow-up and appraisal of curative effect were carried out. Results: At least six months after 131 I therapy, the effective rate of Graves' hyperthyroidism and Graves' ophthalmopathy were 94.3% and 73.3% respectively. The total effective rate of hyperthyroidism with ophthalmopathy was 71.2%. There was a significant correlation between the prognosis of Graves' ophthalmopathy and therapeutic efficacy of hyperthyroidism (r=0.302, P 131 I therapy (χ 2 =0.296, P>0.05). Conclusions: The key to treat Graves' ophthalmopathy is the cure of Graves' hyperthyroidism through 131 I therapy. The timely diagnosis and replacement treatment of hypothyroidism can effectively avoid the aggravation of Graves' ophthalmopathy after 131 I therapy. (authors)

  1. Improvement of the obtention process of 131 I of ININ through studies of equipment design and process parameters fitting in the simulator

    International Nuclear Information System (INIS)

    Zepeda M, M.C.

    2006-01-01

    The main objective of the work was to achieve a high yield of the reaction that happens among the vapors of 131 I and the NaOH to obtain sodium iodide (Na 131 I) in solution optimizing the contact time of the molecules in gaseous state of 131 I with the NaOH molecules through the bubbling velocity of the 131 I in the solution of NaOH 0.1 N, as well as the operation temperature during the distillation process by dry via starting from tellurium dioxide (TeO 2 ) with the purpose of that the 131 I that is obtained in the form of Na 131 I solution presents the necessary quality that allows to distribute it in the market. The particular objectives were: a) To improve the distillation equipment used for the obtaining of 131 I starting from irradiated tellurium dioxide redrawing the dilution system with the purpose of recovering the 131 I in a minimum volume of sodium hydroxide (NaOH). b) To achieve a bigger time of contact among the molecules of 131 I in gaseous state with the molecules of NaOH in solution through the bubbling velocity and of the redrawing of the dilution system. c) To implement the production of 131 I by dry distillation via starting from tellurium dioxide, obtaining it with a high radionuclide and radiochemical purity. d) To obtain 131 I with the necessary specifications that it marks the pharmacopoeia and it can be used with medical ends. (Author)

  2. Intercomparison measurements of activity of 99mTc and 131I in nuclear medicine services at Recife city, Pernambuco state, Brazil

    International Nuclear Information System (INIS)

    Barreto, F.C.P.; Santos, M.A.P dos; Oliveira, M.L.; Lima, F.F. de

    2007-01-01

    The aim of this work is to present the results of the first round of intercomparison measurements of activity of 99m Tc and 131 I. This round was carried out in Recife/PE. Six nuclear medicine services (NMS), public and private, participated in this intercomparison. Additionally to the activity measurement, some information about equipment (calibration and quality control program) and human resources was obtained. All NMS participants complied with the limit established by CNEN for the accuracy of measurement (+- 10%) for 99m Tc and 131 I. Measurements will be repeated for 99m Tc and 131 I, and additional rounds will be performed including different radionuclides. (author)

  3. Comparative study of 131I with 131I plus lithium carbonate in the treatment of Graves' hyperthyroidism

    International Nuclear Information System (INIS)

    Kang Yuguo; Kuang Anren; Guan Changtian

    2003-01-01

    Objective: To evaluate the effects of lithium carbonate on serum TSH, FT 3 , FT 4 and thyroid mass volume in patients with Graves' hyperthyroidism treated with 131 I. Methods: Thirty patients with newly diagnosed, untreated Graves' disease (GD) and nonsevere or absent Graves' ophthalmopathy, were randomly assigned to group 1 and group 2. The 1st group was treated with 131 I therapy only, the 2nd group with 131 I plus lithium carbonate. All subjects were evaluated for changes in serum TSH, FT 3 and FT 4 as well as thyroid mass volume at the 7, 14, 30 d after 131 I therapy. Differences between the two groups in thyroid mass volume, serum FT 4 , FT 3 , and TSH levels at each interval were evaluated by ANCOVA. Results: Serum FT 4 and FT 3 levels increased shortly after 131 I therapy only in group 1, and decreased in group 2. The differences of serum FT 3 and FT 4 levels between the two groups were significant. Conclusion: It is important for GD patients to accept lithium carbonate treatment and 131 I therapy simultaneously in order to decrease the serum FT 3 and FT 4 levels caused by 131 I therapy

  4. Analysis of pelvic 131I uptake after 131I whole body scan in patients with thyroid cancer

    International Nuclear Information System (INIS)

    Kou Ying; Liu Jianzhong; Hao Xinzhong; Wu Lixiang; Lu Keyi; Yang Suyun; Shi Xiaoli; Hu Tingting

    2014-01-01

    Objective: To analyze and explore the possible mechanism for pelvic 131 I uptake after 131 I post treatment whole body scan (Rx-WBS)in patients with differentiated thyroid cancer. Methods: (1) Data were retrospectively reviewed from 168 female patients with differentiated thyroid cancer (everyone has a Rx-WBS). (2) 46 patients were accepted by analyzing the characteristics of Rx-WBS and combing with some inclusion criteria,and then followed up. Results: Among the 46 patients (46 positions accumulated 131 I) with significant pelvic 131 I uptake, 6 patients had two reasons leading to pelvic 131 I uptake, and 2 patients had no specific reason. Among the 50 reasons for pelvic 131 I uptake, 41 reasons related with uterus, 3 reasons related to rectum, 5 related to bladder and 1 related to ovarian chocolate cyst. Among the 41 reasons related to uterus, by combining the examinations of SPECT/CT, ultrasound, CT and the follow-up results, 18 were uterine leiomyomas, 9 were intrauterine devices, 2 were endometrial thickening, 3 were uterine cavity effusion, 7 were menstrual periods, 1 were uterine adenomyosis, 1 were gestational sac. Conclusions: (1) In the Rx-WBS of female, the significant pelvic 131 I uptake is generally caused by uterus, but not bladder. And it usually means gynecological disease, especially uterine leiomyomas when excluding physiological factors. (2) It is generally easy to differentiate bladder from rectum because they have different characteristic features of the pelvic 131 I uptake. (3) SPECT/CT plays a very important role in locating 131 I uptake in uterus. (authors)

  5. Transient hypothyroidism after 131I treatment of Graves disease

    International Nuclear Information System (INIS)

    Liu Jianfeng; Fang Yi; Zhang Xiuli; Ye Genyao; Xing Jialiu; Zhang Youren

    2003-01-01

    Objective: To evaluate the results of the transient hypothyroidism after 131 I treatment of Graves disease. Methods: A total of 32 transient hypothyroidism patients treated with 131 I for Graves disease were studied and followed up. Results: Transient hypothyroidism occurred within 2-6 months after 131 I treatment and 19 patients were symptomatic. At diagnosis of transient hypothyroidism, T 3 and T 4 levels were decreased had normal, TSH levels were increased, normal or low. Follow-up examination found that 20 patients were normal and 12 patients had relapse of hyperthyroidism. Conclusions: Therapy of Graves disease with low doses of 131 I causes a high incidence of transient hypothyroidism. After recovery of transient hypothyroidism, some patients have relapse of hyperthyroidism

  6. Effficacy of 131I therapy hyperthyroidism in adolescent

    International Nuclear Information System (INIS)

    Qin Lan; Wang Junqi; Feng Xuemin; Yin Le

    2004-01-01

    To investigate the possibility of 131 I therapy hyperthyroidism in adolescent, 117 adolescent patients treated with 131 I are analyzed retrospectively. In the first treatment of 131 I, 76 patients gain with euthyroidism (65.0%), 28 patients have remission (23.9%), 13 patients have hypothyroidism (11.0%), the total efficacy is 88.9%. The administered dose to the patients with younger than 14 years is significantly lower than the patients aged from 15 years to 18 years. There is no significantly difference in cure rate or incidence of hypothyroidism between the two groups. The second treatment may improve the cure rate and not exert any significant impact to the incidence of hypothyroidism. Therefore, 131 I treatment hyperthyroidism in younger is efficacious, inexpensive and safe. The dosages given to patients are different between age groups. (authors)

  7. Clinical evaluation of 131I in treatment hyperthyroidism

    International Nuclear Information System (INIS)

    Wang Jing; Deng Jinglan; Qiao Hongqing

    2001-01-01

    The clinical value of 131 I in the treatment of hyperthyroidism is observed. The weight of the thyroid was evaluated by palpation, 131 I was taken orally by one dose method. The dose was calculated by actual absorption of 131 I/per gram of thyroid. 3 - 6 months after drug administration, the symptom, clinical manifestation and the serum hormone of the pituitary-hypothyroid axis were observed. In 105 cases, 80(76.2%) were nearly recovered, among them 16(15.2%) had hypothyroidism in the early period. The all over recovering rate was 91.4% in one dose, but 9(8.6%) were recurred and can be controlled at a second dose. Therefore 131 I for the hyperthyroidism had a high recovering rate, low recurring rate and was very convenient. If prospect on the Chinese effort the controlled, the occurrence of hypothyroidism can be reduced to the acceptable level

  8. {sup 131}I treatment of nodular non-toxic goitre

    Energy Technology Data Exchange (ETDEWEB)

    Nygaard, B.; Faber, J.; Hegdeues, L.; Hansen, J.M. [Herlev Hospital (Denmark)

    1996-01-01

    The traditional treatment of a growing nodular non-toxic goitre has for many years been surgical resection or levothyroxine suppressive treatment. During recent years, several studies have reported promising results of {sup 131}I treatment in terms of thyroid size reduction. This review outlines the different treatment modalities on non-toxic nodular goitre with special emphasis on {sup 131}I treatment. By the term nodular goitre the authors include glands with solitary or multiple thyroid nodules with uptake on a scintiscan. At what point of the natural history of non-toxic multinodular goitre {sup 131}I therapy should be used is not clear. In principle, the best result is obtained in smaller goitres and it is possible that the best effect of {sup 131}I is seen if treatment is given to patients with diffuse goitre before these become nodular. However, then there is a potential risk to swing in the direction to where {sup 131}I is used in an indiscriminate way, since the prevalence of non-toxic multinodular goitre is much higher than that of hyperthyroidism. Although we have data on the long-term hazards of {sup 131}I treatment in hyperthyroidism in terms of risk of cancer, we have only follow-up periods of 5 to 10 years for non-toxic goitres in small groups of patients and no data regarding the long-term risk of high-dose {sup 131}I treatment (>600 MBq) for this condition. Ideally, long term randomized studies comparing the effect, side effect and cost-benefit of surgery as opposed to {sup 131}I treatment should be performed. Awaiting this, it is at present mandatory that each individual patient be given a choice of treatment after proper information. 44 refs.

  9. 131I treatment in patients undergoing renal dialysis: our experience

    International Nuclear Information System (INIS)

    Tobarra, Bonifacio; Campos, Pedro A.; Gonzalez Lopez, Antonio; Palma, Juan D.

    2008-01-01

    Radiation Protection issues concerning patients, public and staff must be considered carefully in hemodialysis for chronic renal failure patients scheduled for 131 I high dose therapy. In order to assess the risks related to this medical procedure, hemodialysis clearance of 131 I and contamination measurements were carried out. We have studied 12 hemodialysis procedures corresponding to 2 cases of hyperthyroidism disease (555MBq of 131 I administered) and 3 patients with carcinoma of the thyroid (5550 MBq of 131 I administered). The arterio-venous difference of 131 I across the artificial kidney and dose rate reduction at one meter of patient were measured. Contamination levels of the dialyser machine, filters and tubes were measured after dialysis with a contamination monitor. Direct read-out dosimeters were used to assess the radiation doses to nursery staff involved. The result obtained for mean 131 I clearance in blood was 75±11%. The mean dose rate reduction at one meter of the patient was 58±18%. We also checked that contamination levels for the dialyser machine, filters, tubes and accessories were lower than 10Bq/cm 2 . For the nursery staff the radiation dose was found to be lower than 0.1mSv. (author)

  10. Breast cancer following 131I therapy for hyperthyroidism

    International Nuclear Information System (INIS)

    Hoffman, D.A.; McConahey, W.M.

    1983-01-01

    A retrospective cohort study of women treated for hyperthyroidism at the Mayo Clinic between 1946 and 1964 was conducted to determine if 1,005 women treated with ( 131 I) were at increased risk of breast cancer compared with 2,141 women traced, and a response (death certificate or questionnaire) was received for 99% of the traced women. The average duration of follow-up was 15 years for the 131 I-treated women and 21 years for women treated surgically. No increased risk of breast cancer was observed in the 131 I-treated women (adjusted relative risk . 0.8). No patterns were found of increased breast cancer risk by age at first treatment, by time since treatment, or by total exposure to 131 I. Failure to detect an increased risk of breast cancer in the 131 I-treated women was attributed to the moderately low doses from 131 I therapy and the relatively small number of exposed women. The study also failed to find any increased risk of breast cancer associated with hyperthyroidism

  11. Management of thyroid carcinoma with radioactive 131I

    International Nuclear Information System (INIS)

    Paryani, Shyam B.; Chobe, Rashmi J.; Scott, Walter; Wells, John; Johnson, Douglas; Kuruvilla, Anand; Schoeppel, Sonja; Deshmukh, Abhijit; Miller, Robert; Dajani, Lorraine; Montgomery, Charles Ted; Puestow, Eric; Purcell, John; Roura, Miguel; Sutton, David; Mallett, Ruth; Peer, Jan

    1996-01-01

    Purpose: To evaluate the role of radioactive 131 I in the management of patients with well differentiated carcinoma of the thyroid. Methods and Materials: Between 1965 and 1995, a total of 117 patients with well-differentiated carcinoma of the thyroid underwent either lobectomy or thyroidectomy followed by 100-150 mCi of 131 I. Results: With a median follow-up of 8 years, only four patients (3%) developed a recurrence of their disease. The 5-year actuarial survival was 97% with a 10-year survival of 91%. There were no severe side effects noted after 131 I therapy. Conclusions: Radioactive 131 I is a safe and effective procedure for the majority of patients with well-differentiated thyroid carcinoma. We currently recommend that all patients undergo a subtotal or total thyroidectomy followed by 131 I thyroid scanning approximately 4 weeks after surgery. If the thyroid scan shows no residual uptake and all disease is confined to the thyroid, we recommend following patients with annual thyroid scans and serum thyroglobulin levels. If there is any residual uptake detected in the neck or if the tumor extends beyond the thyroid, we recommend routine thyroid ablation of 100-150 mCi of radioactive 131 I

  12. Transfer of Chernobyl-derived 134Cs, 137Cs, 131I and 103Ru from flowers to honey and pollen

    International Nuclear Information System (INIS)

    Bunzl, K.; Kracke, W.

    1988-01-01

    The activity concentrations of 137 Cs, 134 Cs, 131 I and 103 Ru were determined separately in honey and pollen samples collected from a single bee colony during several months after the deposition of Chernobyl fallout. The source of each honey and pollen sample was determined by pollen analysis. Although the activity concentrations in honey and pollen varied with time, the concentrations of 137 Cs and 134 Cs were, in general, higher in pollen than in honey. For 103 Ru and 131 I, these differences were comparatively small. The mean 131 I/ 137 Cs and 103 Ru/ 137 Cs ratios were about one order of magnitude higher in honey than in pollen. The mean 131 I/ 103 Ru ratio was about the same for honey and pollen. This observation, in the light of the corresponding nuclide ratios found in the deposition, suggests that 137 Cs, 134 Cs, 131 I and 103 Ru were taken up by the plant leaves and transported to nectar and pollen. The higher activity concentrations of 137 Cs and 134 Cs in pollen, relative to honey, indicate that these radionuclides behave analogously to potassium, which is also found in higher quantities in pollen. (author)

  13. Evaluation of internal occupational exposure of workers from nuclear medicine services by aerosol analysis containing 131I

    International Nuclear Information System (INIS)

    Carneiro, Luana Gomes; Sampaio, Camilla da Silva; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto; Santos, Maristela Souza; Dantas, Bernardo Maranhao; Paula, Gustavo Affonso de

    2014-01-01

    This study evaluated the risk of internal occupational exposure associated with the incorporation of 131 I via inhalation, in Nuclear Medicine Services, using aerosol analysis techniques. Occupationally Exposed Individuals (IOE) involved in handling this radionuclide are subject to chronic exposure, which can lead to an increase in the committed effective dose. Results obtained in preliminary studies indicate the occurrence of incorporation of 131 I by workers involved in handling solutions for radioiodine therapy procedures. The evaluation was carried out in radiopharmacy lab (nuclear medicine service) of a public hospital located in the city of Rio de Janeiro. After confirmed the presence of the radioisotope, by a qualitative assessment, it was determined an experimental arrangement for sample collection and were detected and quantitated the presence of steam 131 I during routine work. The average concentration of activity obtained in this study was 3 Bq / m 3 . This value is below of Derived Concentration in Air (DCA) of 8.4 x 10 3 Bq of 131 I / m 3 corresponding to a committed effective dose of 1.76 x 10 -4 mSv. These results demonstrate that the studied area is safe in terms of internal exposure of workers. However, the presence of 131 I should be periodically reevaluated, since this type of exposure contributes to the increase of the individual effective doses. Based on the data obtained improvements were suggested in the exhaust system and the use of good work practices in order to optimize the exposures

  14. Development and calibration of a portable detection system for in vivo monitoring of {sup 131}I incorporation by humans

    Energy Technology Data Exchange (ETDEWEB)

    Lucena, Eder A.; Dantas, Ana Leticia A.; Dantas, Bernardo M. [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil)], e-mail: eder@ird.gov.br

    2009-07-01

    {sup 131}I is one of the most frequently used radionuclides for diagnosis and therapy of thyroid diseases in nuclear medicine. Its increasing use for medical purposes creates a demand for feasible methodologies applied to the control of internal exposure by workers. In vivo monitoring of {sup 131}I incorporation is of great value for the evaluation of occupational exposure during its medical application and also in the case of accidents and incidents in nuclear power plants for the monitoring of workers and population. This work presents the development of a portable device specially designed for in vivo measurement of {sup 131}I in the thyroid. It is also presented the results of the calibration performed in different nuclear medicine centers where {sup 131}I is routinely manipulated for therapeutic purposes. The equipment consists in a NaI(Tl)3''x3'' detector installed in a lead collimator and assembled on a tripod. The detection system was calibrated with the IRD-Neck-Thyroid phantom for the determination of the calibration factors for direct in vivo quantification of {sup 131}I in the thyroid. In order to evaluate the applicability and limitations of the system, committed effective doses associated to the minimum detectable activities were calculated using current biokinetic and dosimetric models available in the literature. Dose detection limits have shown to be far below 1 mSv for the most likely incorporation scenarios. (author)

  15. The analogy research study on gamma radiation dose rate of radioisotopes 131Ba and 131I

    International Nuclear Information System (INIS)

    Hu Youhua; Feng Guangwen

    2013-01-01

    Analogy is a inference method ,according some properties of a class of things to inferring the similar things should also have the similar properties. The analogy of same radionuclides is widely used in radioisotope logging environment impact assessment so far. This paper is to provide fFor future providing a theoretical calculation method and analogy method between different radionuclides in radioisotope logging environment impact assessment. In this paper, using the latest decay scheme, through theoretical modeling, the aim is the the establishment of 131 Ba and 131 I radioisotopes gamma radiation dose rate calculation method, and try to carry out analogy research on gamma radiation dose rate of different radioisotopes with the same activity. The results show that the analogy of different radionuclides is feasible, which provides the new method reference for carrying out such radiation environmental impact assessment in future. (authors)

  16. Radiological Risk for Patients Treated with 131I

    International Nuclear Information System (INIS)

    Chas, J.; Janiak, M.K.; Kowalczyk, A.; Siekierzynski, M.; Dziuk, E.

    2001-01-01

    Full text: Dose equivalents were measured during the three-day therapy with 131 I in patients treated at the Clinic of Endocrinology and Radioisotope Therapy, Central Clinical Hospital, Military University School of Medicine, Warsaw, Poland, for thyroid cancer (supplementary treatment; 21 cases), hyperthyroidism in the Graves-Basedov's disease (18 cases), and toxic nodular goiter (19 cases). The absorbed doses were measured with thermoluminescent dosimeters placed above the jugular incisure and above the pubic symphysis; the readings were used for calculation of the dose equivalent over the thyroid and in the ovaries. Following the radical treatment of thyroid cancer iodine uptake in the thyroid gland was very low and most of the applied 131 I was excreted within one to three days. In our 21 patients who were given on average 2.8 GBq (76 mCi) 131 I and stimulated with TSH (approx. 60 μIU/mL) the mean dose equivalents over the thyroid and in the ovaries were 115±123 mSv and 56±19 mSv, respectively. In comparison, the calculated dose equivalents in the Graves-Basedov's disease patients (424 MBq mean activity of the applied 131 I) and the goiter patients (544 MBq mean activity of the applied 131 I) were approx. 3.5 times higher over the thyroid and approx. 2.5 times lower in the ovaries. No disfunctions of the ovaries were detected in the treated young women. Based on these results it is recommended to stimulate diuresis during the first two-three days after the injection of 131 I. The results also indicate that exposure to ionising radiation of patients treated for various thyroid disorders with 131 I does not lead to the development of clinically detectable non-stochastic effects. (author)

  17. Improvement of the obtention process of {sup 131} I of ININ through studies of equipment design and process parameters fitting in the simulator; Perfeccionamiento del proceso de obtencion del {sup 131} I del ININ mediante estudios de diseno del equipo y ajustes de parametros del proceso en el simulador

    Energy Technology Data Exchange (ETDEWEB)

    Zepeda M, M C

    2006-07-01

    The main objective of the work was to achieve a high yield of the reaction that happens among the vapors of {sup 131} I and the NaOH to obtain sodium iodide (Na{sup 131} I) in solution optimizing the contact time of the molecules in gaseous state of {sup 131} I with the NaOH molecules through the bubbling velocity of the {sup 131} I in the solution of NaOH 0.1 N, as well as the operation temperature during the distillation process by dry via starting from tellurium dioxide (TeO{sub 2}) with the purpose of that the {sup 131} I that is obtained in the form of Na{sup 131} I solution presents the necessary quality that allows to distribute it in the market. The particular objectives were: a) To improve the distillation equipment used for the obtaining of {sup 131} I starting from irradiated tellurium dioxide redrawing the dilution system with the purpose of recovering the {sup 131} I in a minimum volume of sodium hydroxide (NaOH). b) To achieve a bigger time of contact among the molecules of {sup 131} I in gaseous state with the molecules of NaOH in solution through the bubbling velocity and of the redrawing of the dilution system. c) To implement the production of {sup 131} I by dry distillation via starting from tellurium dioxide, obtaining it with a high radionuclide and radiochemical purity. d) To obtain {sup 131} I with the necessary specifications that it marks the pharmacopoeia and it can be used with medical ends. (Author)

  18. Absorbed dose measurement by the MIRD system in the 131-I treated Thyroid Cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Hong, Seong Woon; Lim, Sang Mu; Kim, Chang Hui; Kim, Ki Sub; Cho, Jong Sio; Jeong, Jin Sung; Park, Heung Kyu; Kwon, Oh Jin [Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    1995-12-01

    Medical Internal Radiation Dose(MIRD) schema was developed for calculating the absorbed dose from the administrated radiopharmaceuticals. With the biological distribution data and physical properties of the radionuclide, we can estimated the absorbed dose by the MIRD schema. For the thyroid cancer patients received high dose 131-I therapy, the absorbed dose to the bone marrow is limiting factor to the administered dose and the duration of admission is determined by the retained activity in the whole body. To the monitoring of whole body radioactivity, we used Eberline Smart 200 system using ionization chamber as a detector. With the time activity (Author).

  19. Rapid measurement of 131I in the thyroid gland using a portable Ge system

    International Nuclear Information System (INIS)

    Kawamura, H.; Kimura, S.

    2000-01-01

    Rapid yet accurate measurement of the 131 I activity in the thyroid gland as well as in the air, water and vegetation may have an important role in obtaining quantitative information on internal doses for the people living in the vicinity of nuclear facilities shortly after an accidental release of radionuclides. Whole body counting technique is still the standard method for measuring radionuclides in the body while necessity for in situ measurement techniques has considerably increased especially after the Three Mile Island and Chernobyl accidents. For measurement of 131 I in the thyroid gland in emergency situations, NaI (Tl) detectors, as in a scintillation survey meter as in the simplest case, are most often used while measurement of urinary excretions for members of the public may also effective. The scintillation survey meter method, being easily implemented, may not have enough selectivity for radioiodine and even be liable to an elevated background radiation spectrum. This would possibly lead to higher detection limits and lower accuracy. A use of a laboratory Ge (Li) detector system in the thyroidal radioiodine measurement was suggested to overcome the problem. A real measurement with a similar instrument was reported for the residents in U.K. after the Chernobyl accident. A use of a scintillation spectro-survey meter with a NaI (Tl) probe with lead collimation to thyroidal radioiodine measurement was also reported to give satisfactorily accurate evaluation of the thyroidal 131 I burden. In this paper, a movable Ge system was developed for the above purpose and preliminarily evaluated particularly for counting efficiency. It is consisted of a portable high-purity Ge detector and a battery-operated MCA. It employs a laboratory made thin Pb shield with a collimation window and an elevator for the detector platform. The elevator was designed to adjust the height of the thyroid radioiodine probe in relation to the height and position of the neck of a subject

  20. Pharmacokinetics of gene recombined angiogenesis inhibitor Kringle 5 in vivo using 131I specific markers and SPECT/CT

    Directory of Open Access Journals (Sweden)

    Ge Yan

    2016-10-01

    Full Text Available The previous pharmacokinetic methods can be only limited to drug analysis in vitro, which provide less information on the distribution and metabolismof drugs, and limit the interpretation and assessment of pharmacokinetics, the determination of metabolic principles, and evaluation of treatment effect. The objective of the study was to investigate the pharmacokinetic characteristics of gene recombination angiogenesis inhibitor Kringle 5 in vivo. The SPECT/CT and specific 131I-Kringle 5 marked by Iodogen method were both applied to explore the pharmacokinetic characteristics of 131I-Kringle 5 in vivo, and to investigate the dynamic distributions of 131I-Kringle 5 in target organs. Labeling recombinant angiogenesis inhibitor Kringle 5 using 131I with longer half-life and imaging in vivo using SPECT instead of PET, could overcome the limitations of previous methods. When the doses of 131I-Kringle 5 were 10.0, 7.5 and 5.0 g/kg, respectively, the two-compartment open models can be determined within all the metabolic process in vivo. There were no significant differences in t1/2α, t1/2β, apparent volume of distribution and CL between those three levels. The ratio of AUC(0~∞ among three different groups of 10.0, 7.5 and 5.0 g/kg was 2.56:1.44:1.0, which was close to the ratio (2:1.5:1.0. It could be clear that in the range of 5.0–10.0 g/kg, Kringle 5 was characterized by the first-order pharmacokinetics. Approximately 30 min after 131I-Kringle 5 was injected, 131I-Kringle 5 could be observed to concentrate in the heart, kidneys, liver and other organs by means of planar imaging and tomography. After 1 h of being injected, more radionuclide retained in the bladder, but not in intestinal. It could be concluded that 131I-Kringle 5 is mainly excreted through the kidneys. About 2 h after the injection of 131I-Kringle 5, the radionuclide in the heart, kidneys, liver and other organs was gradually reduced, while more radionuclide was concentrated

  1. Visualization of adrenocortical carcinoma with 131I-Adosterol

    International Nuclear Information System (INIS)

    Maruoka, Shin; Nakamura, Mamoru

    1987-01-01

    There are very few literatures on successful visualization of adrenocortical carcinoma by means of 131 I-iodocholesterol scintigraphy, although many reports have referred to utility of 131 I-iodocholesterol scintigraphy for adrenal disorders. Since 1976, we have experienced 4 cases of adrenocortical carcinoma which were delineated by 131 I-6β-iodomethyl-19-norcholesterol ( 131 I-Adosterol). Three of 4 cases were adrenocortical carcinoma with Cushing's syndrome, and one was adrenocortical carcinoma with adrenogenital syndrome. In 3 cases of cortisol secreting adrenocortical carcinoma, uptake in the tumor and lack of uptake in the contralateral adrenal gland were seen. Faint to moderate uptakes were observed in the 2 cases, but another one showed as high uptake as seen in adenoma. Patient with androgen secreting adrenocortical carcinoma had increased uptake in the tumor and showed faint uptake in the contralateral adrenal gland. Intensity of 131 I-Adosterol uptake in adrenocortical carcinoma seems to depend on the extent of tumor necrosis, cell differentiation and function. (author)

  2. Visualization of adrenocortical carcinoma with /sup 131/I-Adosterol

    Energy Technology Data Exchange (ETDEWEB)

    Maruoka, Shin; Nakamura, Mamoru

    1987-01-01

    There are very few literatures on successful visualization of adrenocortical carcinoma by means of /sup 131/I-iodocholesterol scintigraphy, although many reports have referred to utility of /sup 131/I-iodocholesterol scintigraphy for adrenal disorders. Since 1976, we have experienced 4 cases of adrenocortical carcinoma which were delineated by /sup 131/I-6US -iodomethyl-19-norcholesterol (/sup 131/I-Adosterol). Three of 4 cases were adrenocortical carcinoma with Cushing's syndrome, and one was adrenocortical carcinoma with adrenogenital syndrome. In 3 cases of cortisol secreting adrenocortical carcinoma, uptake in the tumor and lack of uptake in the contralateral adrenal gland were seen. Faint to moderate uptakes were observed in the 2 cases, but another one showed as high uptake as seen in adenoma. Patient with androgen secreting adrenocortical carcinoma had increased uptake in the tumor and showed faint uptake in the contralateral adrenal gland. Intensity of /sup 131/I-Adosterol uptake in adrenocortical carcinoma seems to depend on the extent of tumor necrosis, cell differentiation and function.

  3. /sup 131/I-meta-iodobenzylguanidine scintigraphy of neuroblastomas

    International Nuclear Information System (INIS)

    Munkner, T.

    1986-01-01

    Sixteen neuroblastoma patients have been studied by /sup 131/I-meta-iodobenzylguanidine scintigraphy. Three patients were possibly cured, and their scintigraphy results were normal. Thirteen patients had tumors and metastases demonstrated by /sup 131/I-MIBG, two of these patients had a normal vanillylmandelic acid excretion levels. One patient has been treated by /sup 131/I-MIBG, but died. /sup 131/I-MIBG was concentrated in other cells too, e.g., in erythrocytes and platelets. Neuroblastoma is the most common solid malignant disease in children. It has a poor prognosis in patients more than one year old. Early detection and a display of the spread of the tumor is of utmost importance for planning and controlling the treatment. Mass screening for neuroblastoma in infants has been suggested and tried in Japan. Scintigraphy after injection of /sup 131/I-meta-iodobenzylguanidine has been used successfully for locating neuroblastomas. An initial study failed to demonstrate neuroblastoma by means of MIBG in two patients. Since the latter part of 1983, MIBG has been used in a number of European centers for imaging neuroblastomas with very promising results, and a multicenter investigation has been initiated. The Ann Arbor group has recently extended its studies to a group of ten patients and has confirmed the European results

  4. Clinical discussion of adrenal scan by 131I-adosterol

    International Nuclear Information System (INIS)

    Kubo, Atsushi

    1976-01-01

    131 I-adosterol adrenal scan was conducted to 31 patients. Clear positive images were obtained at the adrenal gland at the side of cortical adenoma on scintigram in all of 5 patients with primary aldosteronism and 5 patients with Cushing's syndrome. It was found that the quantitative measurements of 131 I-adosterol % uptake and of right-to-left uptake ratio do not only make a regional diagnosis of adrenocortical tumor more positive, but also they make the state of adrenocortical function known to an extent. Adrenal scan is easy to be used, and is non-invasive to patients. The obtained results are diagnostically valuable. It is considered that 131 I-Adosterol is an excellent radiopharmaceutical having the sufficient efficacy for adrenal diseases. (Ichikawa, K.)

  5. 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

  6. Experience by the use of /sup 131/I-19-iodocholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Kinoshita, H; Tsuru, Y; Inazuki, S; Fujimoto, S; Futagawa, S [Nagasaki Univ. (Japan). School of Medicine

    1975-01-01

    Clinical application of /sup 131/I-iodocholesterol to adrenal scintigraphy of the total 50 times was made in 36 patients suggestive of adrenal disease. The index and ratio of bilateral adrenal alands were calculated by ROI processing on the computer scintigram, which was assumed useful for diagnosis of adrenocortical hypofunction as well as its hyperfunction as formerly said. Adrenal scintigraphy with /sup 131/I-iodocholesterol is routine examination which should be positively applied to patients with adrenal cortex disease, because its exposure dose is as small as it matters little except for repeating frequently.

  7. Production technology of 131I-rose bengal

    International Nuclear Information System (INIS)

    Hradilek, P.; Miklik, M.; Kopicka, K.; Kronrad, L.

    1983-01-01

    A detailed description is presented of the production equipment and production process used for Rose Bengal labelled with 131 I designed for use in nuclear medicine. The apparatus was installed in the semi-hot cell laboratory of the Nuclear Research Institute at Rez. The processed activity is around 20 GBq, the average yield of the ion exchange reaction between non-radioactive Rose Bengal and 131 I-labelled sodium iodide is 90%. The unreacted active sodium iodide is separated and the resulting product is diluted and processed into a drug presentation, sterilized and after random control is distributed in 14 days intervals to medical workplaces. (M.D.)

  8. Synthesis and labelling of 19-iodocholesterol 131I

    International Nuclear Information System (INIS)

    Hamada, E.S.

    1979-01-01

    Considering the increasing interest in obtaining agents for vizualization of the adrenal gland with radioisotopic techniques, 19-iodocholesterol was prepared by means of chemical synthesis and radioiodine ( 131 I) introduced by isotopic exchange reaction. The reaction product was identified by determination of the melting point and elementary spectroscopic analysis (infra-red absorption and magnetic nuclear ressonance). Radiochemical analysis of the labelled compound was performed by means of then-layer cromatography in silica-gel. In order to confirm its capacity of concentration in the adrenal gland, the distribution of 19-iodocholesterol 131 I, after intravenous injection, was tested in rats. (Author) [pt

  9. 131I-19-iodocholesterol adrenal scanning in Cushing's syndrome

    International Nuclear Information System (INIS)

    Charbonnel, B.; Chatal, J.F.; Chupin, M.; Guillon, J.

    1976-01-01

    7 patients were investigated: 2 bilateral hyperplasia due to pituitary ACTH excess showed bilateral adrenal activity. 1 post-surgical remnant with recurrent Cushing's syndrome was detected. 1 adenoma showed unilateral intense activity and absent activity in the controlateral gland, even after ACTH treatment. 2 carcinomas were weakly imaged. In 1 case, hepatic metastasis showed 131 I-19-iodocholesterol uptake. Adrenal imaging with 131 I-19-iodocholesterol is not a good procedure for assessing hormonal function. It is a valuable and safe tool in the localization and diagnosis of adrenal lesions causing Cushing's syndrome, perhaps better than radiologic procedures. Radiation dosimetry is acceptable [fr

  10. 131I-6β-iodomethyl-19-norcholesterol scintigraphy in a patient with incidentally discovered adrenal tuberculosis

    International Nuclear Information System (INIS)

    Bardet, S.; Mallmann, V. de; Dupas, B.; Peltier, P.; Deumier, B.

    1994-01-01

    Adrenal tuberculosis is rare and usually diagnosed on clinical signs of adrenal deficiency. We report here the uncommon incidental finding of an adrenal tuberculosis which was investigated in this context by radionuclide imaging with 131 I-6β-iodomethyl-19-norcholesterol. Absence of adrenal uptake which has not yet been reported is discussed in terms of differential diagnosis with the CT scan results. (authors). 10 refs., 2 figs

  11. Stability studies of therapeutic 131I-meta-iodobenzylguanidine (131I-mIBG) using high performance liquid chromatography

    International Nuclear Information System (INIS)

    Murhekar, V.V.; Mathur, Anupam; Pilkhwal, Neelam S.; Prabhakar, G.; Padmanabhan, D.; Sachdev, S.S.

    2014-01-01

    BRIT is a manufacturer and supplier of therapeutic doses (100 mCi) of the radiopharmaceutical 131 I-mIBG to various nuclear medicine centers in India. The therapeutic formulation is of high radioactive concentration (>10 mCi/ml) and is thus prone to radiolytic damage during transport, storage until administration. Earlier stability studies at this laboratory were done using conventional methods like Thin Layer Chromatography (TLC) which has an inherent limitation in terms of resolution. In view of this, a suitable HPLC method has been developed and the stability of therapeutic 131 I-mIBG was monitored at various conditions

  12. Unremitted hyperthyroidism following 131I treatment: an analysis of clinical markers in 48 patients

    International Nuclear Information System (INIS)

    Fang Yi; Zhang Xiuli; Liu Jianfeng; Zhang Youren

    2002-01-01

    Objective: To evaluate changes in clinical markers of unremitted hyperthyroidism patients after the first 131 I treatment. Methods: Forth eight unremitted hyperthyroidism patients were selected. Their thyroid function, the peak of 131 I uptake rate and thyroid weight before and after 131 I treatment were compared. Results: TT 3 , TT 4 , TSH were relatively stable and the peak of 131 I uptake rate and thyroid weight were reduced after 131 I treatment. Conclusions: Thyroid volume was reduced after 131 I treatment even if patients' clinical symptoms still existed; the peak of 131 I uptake rate was reduced after 131 I treatment, suggesting that their sensibility to 131 I decreased, so the absorbed dose should be adjusted when the 131 I dosage of second treatment is calculated

  13. Synthesis and labelling of 131-I 19-iodocholesterol

    International Nuclear Information System (INIS)

    Barberio, J.C.

    1978-10-01

    The technique for the preparation of ( 131 I)-19-Iodocholesterol is described. The identification of the synthesized compound was made by spectroscopic, chemical and radiochemical techniques. Biological distribution studies in mice demonstrate that the compound can be used for the diagnosis of tumours and hyperplasia of suprarenal glands

  14. Therapeutic Effect of 131I for 230 Patients with Hyperthyroidism

    International Nuclear Information System (INIS)

    He Yujie; Zhang Chengxi; Hu Jiqing; Guo Sihui; Yuan Hui; Li Jing

    2009-01-01

    To evaluate the therapeutic effect of 131 I in treatment of patients with hyperthyroidism and analysis the factors that influence the effect, 230 cases of hyperthyroidism were treated with 131 I, and were followed-up at 1.5, 3, 6, 12 months and even longer time after 131 I radiotherapy. The serum levels of FT3, FT4 and TSH were detected in all cases. The results showed that 181 patients were cured (78.6%), 22 patients were improved (9.5%), 23 cases developed early hypothyroidism(10.0%),and 4 cases developed later hypothyroidism. 12 cases in 27 patients with hypothyroidism treated with thyroxin were recovered, but the other 15 cases need to be given permanent treatment. The factors which influence 131 I radiotherapeutic effect include the patient age, course of disease,application of ATD, size and quality of thyroid, and the level of thyroid hormone. The patients should be followed up to prevent occurrence of hypothyroidism. The early hypothyroidism should be treated in order to decrease the permanent hypothyroidism rate. (authors)

  15. Determination of 131I and thorium in urine

    International Nuclear Information System (INIS)

    Tomida, Rute Miwa

    1978-01-01

    Methods for the determination of 131 I and Thorium in urine have been developed taking into account the monitoring needs for people who handle with these radioisotopes. The method for determining 131 I is based in the use of silver chloride to separate iodine by precipitation from the sample; the detection was carried out in a Nal (Tl) well type scintillator connected to a single channel analyser. This method has the following advantages; it is easy and relatively fast as well as selective, showing a separation yield higher than 80%. Thorium in urine was determined by colorimetry after the mineralization of the sample using nitric acid, and sulphuric acid, and then oxygen peroxide. The chromophore reagent used was Thoron (disodium salt of 2-(2-hydroxy-3,6-disulfo-l-naphthylazo) benzenearsonic acid).The absorbance was measured in a spectro colorimeter at a fixed wavelength (530 nm). The method proved to be simple allowing a separation yield of about 80%. The most representative sample for a monitoring program in a 131 I production laboratory has been established. The 131 I concentration in urine of individuals with chronic contamination have also been measured; an interpretation of these results is discussed. (author)

  16. Longterm results of 131I treatment of hyperthyroidism

    International Nuclear Information System (INIS)

    Hamada, Noboru; Ito, Kunihiko; Mimura, Takashi; Nishikawa, Yoshihiko; Momotani, Naoko

    1979-01-01

    The results of 131 I treatment were analyzed in 512 out of 1,620 cases of hyperthyroid patients treated with 131 I from 1963 to 1967 at Ito Hospital, Tokyo. The incidence of hypothyroidism, diagnosed clinically referring serum T 3 , T 4 and metabolic index, was 28.5%, euthyroidism 66.4% and hyperthyroidism 5.1%. Fourty one percent of euthyroid cases had high levels of serum TSH. While TRH tests were performed in 11 euthyroid cases with normal TSH levels, TSH response was normal in only 3 of the cases. Since there was no difference in the incidence of hypothyroidism among patients receiving a single dose of 6,001 - 7,000, 7,001 - 8,000 and 8,001 - 9,000 rads, relationship between the results of therapy and various factors which might influence the outcome of therapy was investigated in these cases. The incidence of hypothyroidism was higher in patients with shorter period between the onset of hyperthyroid symptoms and 131 I therapy, previous therapy with external irradiation, small goiter, severe exophthalmus, and shorter effective half life of 131 I at the time of treatment. Three cases of thyroid cancer and 2 cases of leukemia were observed in 823 patients which included 311 cases followed up only by inquiry. (author)

  17. Fixed dose 131-I treatment in Basedow patients

    International Nuclear Information System (INIS)

    Klisarova, A; Bochev, P.; Hristosov, K.

    2003-01-01

    The choice of a treatment for Basedow patients is still unsolved problem. The treatment with 131-I has certain advantages but the determination of the individual therapeutic dose is impossible. The aim of the study is to assess the efficiency of the treatment with a fixed dose. 23 patient have been treated, 30 women and 3 men, age between 48 and 78. All patients are with chronic disease with relapses (1 to 4 relapses). 5 of the patients are with a thyrotoxic heart, 3 - with ophtalmopatia, 2 - with toxic medicamentous hepatitis and 2 with allergies to thyreostatics. Before the treatment with 131-I all patients have been in euthyroid state with normal levels of the peripheral hormones. All patients have received initial doses of 5 mCi 131-I. The hormone levels have been followed on 3rd, 6th, 12th and 24th month after the uptake. From a total of 23 patients, in 3 cases a transitional hypothyroidism has been found between 3th and 6th month, in 3 patients - permanent hypothyroidism. In 5 patients after the 6th month an additional dose of 5 mCi 131-I is given (in one woman a permanent hypothyroidism is reached). Four of the patients have been with a significant thyroid hyperplasia with volume above 60 ml. In three patients in the period between 6th and 12th month a slight hyperthyroidism is registered, which have been suppressed by a low dose thyreostatic. A year after the treatment they have been found euthyroid. The decision for giving a second dose have been based on the evident heptahydrate symptomatic s and the persisting increased thyroid volume. In one case it is observed an acute thyrotoxicosis for 3-5 days after the 131 I uptake. No cases of worsening of the eye symptoms are observed. In conclusion, the treatment with 131 I is a appropriate method for patients with cardiovascular complications, contraindication for surgery or side effects of the thyreostatic treatment. the dose od 5 mCi is sufficient for patients with mild to medium form of Basedow disease and a

  18. 131I therapy for hyperthyroidism with large goitre

    International Nuclear Information System (INIS)

    Zhang Chenggang

    2002-01-01

    Objective: This retrospective analysis is to study the effects of radioiodine in hyperthyroidism with large goitre and observe the possibility to take the place of surgery. Methods: 82 patients (pts) with hyperthyroidism including 51 female and 31 male, age ranging from 11 to 75 years old (mean 35.43 ± 12.14), were treated with 131 I. All patients presented with typical clinical and biochemical hyperthyroidism and were followed up for 3-38 months after 131 I treatment. Patients were categorized into 2 diagnostic groups: Graves disease (43 pts) and toxic multinodular goitres (39 pts). Gland weights were estimated by palpation and scintigraphy. Cold nodule had not been found in scintigraphy in all pts. The dose in mCi administered were determined according to therapeutic history, thyroid weight (g), rate of uptake 131 I, patient's symptoms and course of disease, etc. 76 pts (92.7%) had iII degree goitre. Goitre weight was stratified into 150-200 g (67 pts), 201-300 g (13 pts) and 400-500 g (2pts). 71 pts (86.6%) were given one dose of 131 I, 10 pts (12.2%) two doses, one patient had three doses. The mean first dose was 39.26 ± 19.63 mCi (14-130 mCi). The mean first μCi/g was 142.89±32.29 μCi (59-200). Results: 24 pts (29.3%) had complete remission (euthyroid), 19 pts (23.2%) had partial resolution. 39 (47.6%) pts had hypothyroidism (HP) including 8 permanent HP, 11 transient HP, 3 subclinical HP and 17 indeterminate HP. The later group had HP that could not be decided to be transient or permanent because the time of following up was less than one year. After 131 I therapy, goitres of 43 pts (52.4%) became 0 degree, 34 pts (41.5%) became I degree, 4 pts (4.9%) had II degree and only one pt still had a III degree goitre. Conclusions: 131 I therapy is a safe and effective method for treating hyperthyroidism with large goitre. If the large goitre does not have cold nodule in scintigraphy, 131 I treatment may replace surgery

  19. 131I intake survey and effective dose calculation for personnel in a nuclear medicine department; Vigilancia de incorporaciones de 131I y estimacion de dosis efectiva comprometida en el personal de un servicio de medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez-Laguna, A.; Estrada-Lobato, E.; Brandan, M.E.; Medina, L.A.

    2010-07-01

    The staff of a nuclear medicine department is subject to the risk of 131I intake as consequence of oversights in the radiation safety procedures, the occurrence of an accident, or malicious acts. The intake can be estimated by using a detection system based on NaI(Tl) or HpGe. This paper presents a methodological proposal for the use of a gammacamera for detection of occupational intakes of 131I in the Nuclear Medicine staff. We used a Siemens e.cam gamma camera (GC) as the radionuclide intake detection system. GC sensitivity and minimum detectable activity were determined to quantify activity retained in the thyroid gland. A whole-body anthropomorphic phantom REMCAL was also used to simulate and quantify the intake in the thyroid gland. To estimate the minimal uptake and the minimal committed effective dose E(50) that can be quantified with the gammacamera, the AIDE (Activity and Internal Dose Estimates) software was used. The gammacamera can detect 131I activity in thyroid, as low as 175 Bq without collimators, and 5948 Bq with high-energy collimators. The calculation of E(50) shows to be as low as 5% of the annual limit. This work has shown the utility of the gammacamera to detect intakes of 131I and to estimate the E(50). (Author).

  20. Evaluation of {sup 131}I retention in several adsorbers

    Energy Technology Data Exchange (ETDEWEB)

    Catanoso, Marcela F.; Osso Junior, Joao Alberto, E-mail: marcela.forli@gmail.co, E-mail: jaosso@ipen.b [Instituto de Pesquisas Energeticas e Nucleares (IPEN/CNEN-SP), Sao Paulo, SP (Brazil). Diretoria de Radiofarmacia

    2011-07-01

    Several iodine radioisotopes are used in nuclear medicine for treatment and diagnostic purposes. The radioisotope {sup 131}I is used both in diagnosis and therapy due to its physical characteristics of decay by {beta}{sup -} and its {gamma}-ray emissions suitable for diagnosis. It is routinely produced at IPEN through the irradiation of TeO{sub 2} targets in the IEA-R1m nuclear reactor. After the irradiation, the {sup 131}I is separated by dry distillation, where the targets are put in an oven, heated at 760 deg C for 2 hours and the {sup 131}I, volatile, is carried by an O{sub 2} gas stream. The aim of this work was to evaluate the retention and elution of {sup 131}I samples produced at IPEN in several adsorbers as part of a project aiming the purification of these radioisotopes, allowing the labeling of biomolecules. Samples of {sup 131}I were used for retention and elution studies with the following adsorbers: commercial cartridges, anionic resin columns and cationic resin column. The results showed that Ag cartridges and anionic resins Dowex 1X8, Dowex 3 and IRA 400 had a great iodine retention but no elution after using specific eluents. The QMA light, acid alumina, neutral alumina and cationic resin Dowex 50WX4 showed high retention and elution and QMA plus and cationic resin Dowex 50WX8 and Dowex 50WX12 had a good retention but lower elution. Regarding to the better retention and elution, Ag cartridges and resins showed a higher percentage of iodine retention but lower elution yield and QMA light, acid and neutral alumina cartridges showed better results. (author)

  1. Evaluation of 131I retention in several adsorbers

    International Nuclear Information System (INIS)

    Catanoso, Marcela F.; Osso Junior, Joao Alberto

    2011-01-01

    Several iodine radioisotopes are used in nuclear medicine for treatment and diagnostic purposes. The radioisotope 131 I is used both in diagnosis and therapy due to its physical characteristics of decay by β - and its γ-ray emissions suitable for diagnosis. It is routinely produced at IPEN through the irradiation of TeO 2 targets in the IEA-R1m nuclear reactor. After the irradiation, the 131 I is separated by dry distillation, where the targets are put in an oven, heated at 760 deg C for 2 hours and the 131 I, volatile, is carried by an O 2 gas stream. The aim of this work was to evaluate the retention and elution of 131 I samples produced at IPEN in several adsorbers as part of a project aiming the purification of these radioisotopes, allowing the labeling of biomolecules. Samples of 131 I were used for retention and elution studies with the following adsorbers: commercial cartridges, anionic resin columns and cationic resin column. The results showed that Ag cartridges and anionic resins Dowex 1X8, Dowex 3 and IRA 400 had a great iodine retention but no elution after using specific eluents. The QMA light, acid alumina, neutral alumina and cationic resin Dowex 50WX4 showed high retention and elution and QMA plus and cationic resin Dowex 50WX8 and Dowex 50WX12 had a good retention but lower elution. Regarding to the better retention and elution, Ag cartridges and resins showed a higher percentage of iodine retention but lower elution yield and QMA light, acid and neutral alumina cartridges showed better results. (author)

  2. Methods and results of reconstruction of 131I concentration in milk from total beta-activity measurements in Belarus after Chernobyl

    International Nuclear Information System (INIS)

    Savkin, Mikhail; Shinkarev, Sergey; Titov, Alexey

    2008-01-01

    Full text: During the first few weeks following the Chernobyl accident a large scale monitoring of radioactive contamination of foodstuffs locally produced was carried out in the most contaminated areas of Belarus. Due to a lack of spectrometric instruments, radiometric devices (DP-100) were used for beta activity measurements mostly of milk and milk products. Because the intake of 131 I with milk was the main contributor of the thyroid dose for the Belarus population, it is very important to reconstruct levels of 131 I in milk for Belarus settlements. The purpose of the paper is to present the methods and results of assessing the 13I concentration in milk based on historical records of total-beta activity measurements carried out in April-June 1986 in Belarus. The results of reconstruction of the 131 I concentration in milk will be used in on-going epidemiologic studies of a cohort of Belarus children. About 20,000 total-beta activity measurements were used in the analysis; for about 50% of those, the measurement result exceeded the minimum detectable activity. Estimates of 131 I concentration in milk at the date of sampling and of time-integrated milk concentrations were reconstructed for 482 settlements in Gomel Oblast and for 100 settlements in Mogilev Oblast, the most contaminated areas in Belarus, where at least one milk measurement was available. The assessment of the 131 I concentrations in milk involved: 1) An analysis of the calibration coefficients of the detectors for radionuclides available in milk (the main radionuclides were 131 I, 132 4Cs, 137 Cs, 89 Sr, 90 Sr); and 2) An assessment of the relative activity distribution of those radionuclides in milk. Only measurements made before 21 May 1986 were considered to be reliable, as the measurements conducted late May and in June were found to be unreliable because of the decrease in 131 I concentrations and the growing influence of other radionuclides with longer half-lives. Analysis of multiple

  3. Estimation of Speciation and Distribution of {sup 131}I in urban and natural Environments

    Energy Technology Data Exchange (ETDEWEB)

    Hormann, Volker; Fischer, Helmut W. [University of Bremen, Institute of Environmental Physics, Otto-Hahn-Allee 1, 28359 Bremen (Germany)

    2014-07-01

    {sup 131}I is a radionuclide that may be introduced into natural and urban environments via several pathways. As a result of nuclear accidents it may be washed out from air or settle onto the ground by dry deposition. In urban landscapes this is again washed out by rain, partly introduced into the sewer system and thus transported to the next wastewater plant where it may accumulate in certain compartments. In rural landscapes it may penetrate the soil and be more or less available to plant uptake depending on chemical and physical conditions. On a regular basis, {sup 131}I is released into the urban sewer system in the course of therapeutic and diagnostic treatment of patients with thyroid diseases. The speciation of iodine in the environment is complex. Depending on redox state and biological activity, it may appear as I{sup -}, IO{sub 3}{sup -}, I{sub 2} or bound to organic molecules (e.g. humic acids). Moreover, some of these species are bound to surfaces of particles suspended in water or present in soil, e.g. hydrous ferric oxides (HFO). It is to be expected that speciation and solid-liquid distribution of iodine strongly depends on environmental conditions. In this study, the speciation and solid-liquid distribution of iodine in environmental samples such as waste water, sewage sludge and soil are estimated with the help of the geochemical code PHREEQC. The calculations are carried out using chemical equilibrium and sorption data from the literature and chemical analyses of the media. We present the results of these calculations and compare them with experimental results of medical {sup 131}I in waste water and sewage sludge. The output of this study will be used in future work where transport and distribution of iodine in wastewater treatment plants and in irrigated agricultural soils will be modeled. (authors)

  4. Evaluation of internal occupational exposure of workers from nuclear medicine services by aerosol analysis containing {sup 131}I; Avaliacao da exposicao interna de trabalhadores em servicos de medicina nuclear atraves da analise de aerossois contendo {sup 131}I

    Energy Technology Data Exchange (ETDEWEB)

    Carneiro, Luana Gomes; Sampaio, Camilla da Silva; Dantas, Ana Leticia Almeida; Lucena, Eder Augusto; Santos, Maristela Souza; Dantas, Bernardo Maranhao, E-mail: carneiro@ird.gov.br [Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ),Rio de Janeiro, RJ (Brazil); Paula, Gustavo Affonso de [Escola SESC de Ensino Medio, Rio de Janeiro, RJ (Brazil)

    2014-07-01

    This study evaluated the risk of internal occupational exposure associated with the incorporation of {sup 131}I via inhalation, in Nuclear Medicine Services, using aerosol analysis techniques. Occupationally Exposed Individuals (IOE) involved in handling this radionuclide are subject to chronic exposure, which can lead to an increase in the committed effective dose. Results obtained in preliminary studies indicate the occurrence of incorporation of {sup 131}I by workers involved in handling solutions for radioiodine therapy procedures. The evaluation was carried out in radiopharmacy lab (nuclear medicine service) of a public hospital located in the city of Rio de Janeiro. After confirmed the presence of the radioisotope, by a qualitative assessment, it was determined an experimental arrangement for sample collection and were detected and quantitated the presence of steam {sup 131}I during routine work. The average concentration of activity obtained in this study was 3 Bq / m{sup 3}. This value is below of Derived Concentration in Air (DCA) of 8.4 x 10{sup 3} Bq of {sup 131}I / m{sup 3} corresponding to a committed effective dose of 1.76 x 10{sup -4} mSv. These results demonstrate that the studied area is safe in terms of internal exposure of workers. However, the presence of {sup 131}I should be periodically reevaluated, since this type of exposure contributes to the increase of the individual effective doses. Based on the data obtained improvements were suggested in the exhaust system and the use of good work practices in order to optimize the exposures.

  5. Equipment and obtention process of {sup 131}I by dry distillation starting from TeO{sub 2}; Equipo y proceso de obtencion de {sup 131}I por destilacion seca a partir de TeO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Alanis M, J [ININ, Departamento de Materiales Radiactivos, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2000-08-15

    The present invention refers to an equipment and process for the obtaining of {sup 131}I by dry distillation starting from TeO{sub 2} that has three interconnected systems, the manipulation system, the electric system and the distillation system, the combination of these systems, allows to improve the yield and the separation of the {sup 131}I during the distillation process, since inside the electric system it is an oven that has a special design based on a temperature gradient. The more relevant aspects of the equipment its are the design of each one of its components that give as result the effectiveness of the production of {sup 131}I in routinary form (industrial) whose final product can end up reaching a radiochemical purity up to 99% and a radionuclide purity of approximately 100%. The object of this invention is to provide a distillation equipment different to those that at the moment exist, thanks to its novel internal construction whose main characteristics already gather advantages on those existent. The reaction of obtaining of the TeO{sub 2}, the development of the technique and studies of TeO{sub 2} sintering and the irradiation experiments, its contributed to characterize with more precision the 'new process of obtaining of {sup 131}I by dry via starting from the Te' developed in the ININ, and in this way it was achieved a more pure product, more economic, with less risks, from a point of view of Radiological Safety and mainly that it avoids the import to the country and it makes to self-sufficient Mexico in the production of {sup 131}I. (Author)

  6. Equipment and obtention process of {sup 131}I by dry distillation starting from TeO{sub 2}; Equipo y proceso de obtencion de {sup 131}I por destilacion seca a partir de TeO{sub 2}

    Energy Technology Data Exchange (ETDEWEB)

    Alanis M, J. [ININ, Departamento de Materiales Radiactivos, 52045 Ocoyoacac, Estado de Mexico (Mexico)

    2000-08-15

    The present invention refers to an equipment and process for the obtaining of {sup 131}I by dry distillation starting from TeO{sub 2} that has three interconnected systems, the manipulation system, the electric system and the distillation system, the combination of these systems, allows to improve the yield and the separation of the {sup 131}I during the distillation process, since inside the electric system it is an oven that has a special design based on a temperature gradient. The more relevant aspects of the equipment its are the design of each one of its components that give as result the effectiveness of the production of {sup 131}I in routinary form (industrial) whose final product can end up reaching a radiochemical purity up to 99% and a radionuclide purity of approximately 100%. The object of this invention is to provide a distillation equipment different to those that at the moment exist, thanks to its novel internal construction whose main characteristics already gather advantages on those existent. The reaction of obtaining of the TeO{sub 2}, the development of the technique and studies of TeO{sub 2} sintering and the irradiation experiments, its contributed to characterize with more precision the 'new process of obtaining of {sup 131}I by dry via starting from the Te' developed in the ININ, and in this way it was achieved a more pure product, more economic, with less risks, from a point of view of Radiological Safety and mainly that it avoids the import to the country and it makes to self-sufficient Mexico in the production of {sup 131}I. (Author)

  7. Hypothyroidism caused by 131I treatment for Graves disease

    International Nuclear Information System (INIS)

    Deng Shouzhen; Lin Xiangtong; He Wanting; Zhang Kaili; Zhang Jinming; Kuai Dayu

    1991-01-01

    The refollow-up has been carried out in hypothyroidism caused by 131 I treatment for Graves disease. The serum HS-TSH(IRMA), FT3, TSH(RIA), TT3, TT4, FT4I, MCA, TGA, Cholesterol and Triglyceride has been measured in 26 patient after 131 I treatment for 9.5 years in average. At the same time TRH stimulation test was also performed, and the clinical symptoms and signs assessed. The results showed that TSH is the most sensitive criterion for hypothyroidism, followed by Cholesterol and FT 4 I. The occurence of hypothyroidism may be related to the presence of thyroid antibody as demonstrated by the elevation of serum MCA, TGA. Therefore measurement of serum TSH, FT 4 I and Cholesterol during long term follow-up is beneficial for early diagnosis of hypothyroidism and evaluating the effect of substitution treatment

  8. Hypothyroidism in patients after thyroid elimination by 131I

    International Nuclear Information System (INIS)

    Vana, S.; Nemec, J.; Reisenauer, R.

    1979-01-01

    Patients after elimination of the thyroid gland with radioiodine 131 I develop hypothyroidism only slowly, the peripheral parameters lagging behind the protein bound iodine especially till the fiftieth day after elimination. In young patients the Achilles tendon reflex and the preejection period lag behind symmetrically, in older patients the effect of the supply of thyroid hormones to the skeletal muscles disappear faster, whereas the heart retains the reserves of the thyroid hormones or systems dependent on thyroid hormones affecting the rapidity of myocardial contraction for a relatively longer period of time. Thus, in older patients after elimination of the thyroid gland with radioiodine 131 I the Achilles tendon reflex is a better criterion of hypothyroidism than the preejection period of heart contraction. (author)

  9. Synthesis labeling and biological studies of 16-131I

    International Nuclear Information System (INIS)

    Sato, M.K.

    1988-01-01

    The increasing interest in obtaining radiopharmaceuticals for metabolic imaging of heart muscle led us to prepare 16-IODINE HEXADECANOIC ACID by tosilation of the corresponding hydroxy acid, following iodination with NaI and finally, introducing radioiodine (Na 131 I) by isotopic exchange reaction. The reaction products were identified by determination of melting point, elementary and spectroscopic analysis such as infra-red absortion and magnetic nuclear resonance. The radiopharmaceutical after radiochemical and other specific control procedures for injetable such as sterility and apyrogenicity, was firstly utilized in dogs: preferencial uptake by the heart, as well as by the liver was confirmed. Then, studies in patients with or without heart diseases were performed. The biodistribution of 16- 131 I-HEXADECANOIC ACID was carried out in Wistar rats. The scintigraphic images in animals and in humans demonstrated that 16- 131 -HEXADECANOIC ACID is suitable for studying viable areas as well as energetic exchange of heart muscle. (author) [pt

  10. 131I release from a HTGR during the LOFC accident

    International Nuclear Information System (INIS)

    Foley, J.E.

    1975-03-01

    The time-dependent release of 131 I from both the core and the containment building of a high temperature gas-cooled (HTGR) reactor during the loss of forced coolant (LOFC) accident is studied. A simplified core release model is combined with a containment building release model so that the total amount of the isotope released to the environment can be calculated. The time-dependent release of 131 I from the core during the LOFC accident is primarily a function of the time-dependent core temperatures and the failed fuel release constants. The most important factor in calculating the amount of the isotope released to the environment is the total amount released into the containment building. (U.S.)

  11. 131I metabolism in the study of antithyroid drug

    International Nuclear Information System (INIS)

    Gagliardi, R.P.; Santalla de Pirovano, M. del C.; Kramar de Valmaggia, E.P.; Valsecchi, R.; Pisarev, Mario; Altschuler, Noe

    1977-11-01

    The main purpose of the present report was to study the action of antithyroid drugs on different parameters of thyroid activity utilizing 131 I, in the offsprings of rats treated during pregnancy and the perinatal period. Both PTU and MMI caused alterations in growth and thyroid activity, but they were more dramatic with the former. A significative increase in 131 I thyroid uptake and in circulating radioactivity was observed. When % uptake was expressed as a function of thyroidal and body weights, a significative decrease was noticed. The ratio T/S and the percentage of labelled iodothyronines in pancreatin digests were also decreased. Neuromuscular maturation was evaluated, by means of the test of Schapiro. A group of animals treated with PTU plus T 4 had a significant delay, reaching normal developement later than the controls or those treated with MMI. (author) [es

  12. Cancer of the thyroid and 131I fallout in Norway

    International Nuclear Information System (INIS)

    Oftedal, P.; Lund, E.

    1983-01-01

    From 1953 to 1962 Norway received relatively high levels of radioactive fallout. On the basis of extensive measurements in air, precipitation, food and humans, the dose to the thyroid due to 131 I has been calculated. Cancer registration in Norway is practically completely efficient because of obligatory notification of the Cancer Registry by physicians, pathology laboratories, and the Central Bureau of Statistics of all cases or death certificates concerning cancer. Analysis of the Cancer Registry data from 1953 to 1980 concerning birth cohorts 1936 to 1961 indicates an overall increasing trend in thyroid cancer morbidity, most pronounced in female cohorts born 1930-50. The highest, most abrupt irregularities reveal a coincidence of high numbers with high 131 I content in milk consumed during the years of prepuberty and puberty. Possible interpretations are discussed. (author)

  13. 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.)

  14. 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)

    Cheal, Sarah M.; Lee, Sang-gyu; Punzalan, Blesida; Larson, Steven M.; Xu, Hong; Guo, Hong-fen; Chalasani, Sandhya; Carrasquillo, Jorge A.; Fung, Edward K.; Jungbluth, Achim; Zanzonico, Pat B.; O'Donoghue, Joseph; Smith-Jones, Peter M.; Wittrup, K.D.; Cheung, Nai-Kong V.

    2016-01-01

    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 177 Lu-or 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 177 Lu-DOTA-Bn) were safe and effective, with a complete response of established s.c. tumors (100 - 700 mm 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 3 tumor recurrence. In addition, PRIT dosimetry/diagnosis was performed by PET imaging of the positron-emitting DOTA hapten 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.)

  15. Biological evaluation of 177Lu-labeled DOTA-Ala(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 for gastrin-releasing peptide receptor-positive prostate tumor targeting

    International Nuclear Information System (INIS)

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

    2015-01-01

    Bombesin binds with selectivity and high affinity to a Gastrin-releasing peptide receptor (GRPR), which is highly overexpressed in prostate cancer cells. The present study describes the in vitro and in vivo biological characteristics of DOTA-Ala(SO 3 H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH 2 (DOTA-sBBNA), an antagonist analogue of bombesin peptide for the targeting of GRPR. DOTA-sBBNA was synthesized and labeled with 177 Lu as previously published. A saturation assay on PC-3 human prostate cancer cells revealed that the Kd value of the radiolabeled peptide was 1.88 nM with a maximum binding capacity (Bmax) of 289.3 fmol/10 6 cells. The radio-peptide slowly internalized, and 24.4 ± 0.5% of the total binding was internalized in 4 hr. Biodistribution studies were conducted in healthy and PC-3 xenografted balb/c mice, which showed high uptake and retention of tumor-associated radioactivity in PC-3 xenografted mice. The tumor-to-blood ratio was 126.02 ± 9.36 at 1.5 hr p.i., and was increased to 216.33 ± 61.58 at 24 hr p.i., which means that the radiolabeled peptide was highly accumulated in a tumor and rapidly cleared from the blood pool. The GRPR is also over-expressed in Korean prostate cancer patients. These results suggest that this 177 Lu-labeled peptide has promising characteristics for application in nuclear medicine, namely for the diagnosis and treatment of GRPR over-expressing prostate tumors

  16. Hypertension complicating 131I-meta-iodobenzylguanidine therapy for neuroblastoma

    International Nuclear Information System (INIS)

    Kosmin, Michael A.; Cork, Nicholas J.; Gaze, Mark N.; Bomanji, Jamshed B.; Shankar, Ananth

    2012-01-01

    Radiolabelled meta-iodobenzylguanidine (mIBG), used as targeted therapy for neuroblastoma, is known to have effects on blood pressure (BP). In this study we audited BP changes in patients receiving 131 I-mIBG therapy for neuroblastoma to identify BP-related adverse events (AE) and possible predictive factors. Between 2003 and 2010, 50 patients with neuroblastoma received 110 131 I-mIBG administrations. BP measurements before and after administration were compared with age- and sex-matched centile values. AE were analysed, and possible predisposing factors identified. This population had a baseline BP distribution higher than that of their age- and sex-matched peers, with 16% of preadministration systolic BP values above the 95th centile. Changes in BP after administration showed an approximately normal distribution with similar numbers of reduced and increased values. Four AE, all related to hypertension, occurred with one patient having generalized seizures. One AE was immediate, others occurred between 20 and 25 h after administration. No significant association between AE and patient age or sex was demonstrated. However, a significant association between AE and high preadministration BP was shown, both above the 90th centile (p = 0.0022) and above the 95th centile (p = 0.0135). Clinically relevant hypertension following 131 I-mIBG therapy affected less than 5% of administrations, but was more common in those patients with preexisting hypertension. As hypertensive episodes may occur many hours after treatment, close monitoring of BP needs to be continued for at least 48 h after administration of 131 I-mIBG. (orig.)

  17. 131I albumin of patients carrying progressive systemic sclerosis study

    International Nuclear Information System (INIS)

    Cossermelli, W.; Carvalho, N.; Papaleo Netto, M.

    1974-01-01

    131 I albumin metabolic changes were studied in 14 female patients with progressive systemic sclerosis. A statistical study of the gathered data disclosed increased distribution and turnover half-life and diminished turnover rate of radioactive substance. Since T/2 of turnover and turnover rate are the result produced by the albumin synthesis and degradation, they are probably lowered during active disease causing hypoalbuminemia. The aminoacids also are probably absorbed by other protein like the gammaglobuline synthesis [pt

  18. 131I-19-iodocholesterol scintigraphy and suprarenal pathology

    International Nuclear Information System (INIS)

    Leger, F.A.; Baulieu, J.L.; Plouin, P.F.

    The methods used and results obtained by 131 I-19-iodocholesterol scintigraphy (dose 2mCi) are given for 24 patients with various kinds of suprarenal hyperactivity (primary hyperaldosteronism, Cushing's syndrome, malignant adrenocortical tumour, pheochromocytoma). The morphological and quantitative aspects of suprarenal scintigraphy are examined. A technique to determine the iodocholesterol uptake ratio of the two adrenal glands, considered more important than the fixation rate of each is described [fr

  19. The {sup 131}I cytogenetic effect preceded by the REC-HTSH administration in Wistar rats; Efeito citogenetico do {sup 131}I precedido por administracao de Rec-hTSH em ratos Wistar

    Energy Technology Data Exchange (ETDEWEB)

    Silva, Marcia Augusta da [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)]|[Centro Universitario Sao Camilo, Sao Paulo, SP (Brazil); Ribela, Maria Teresa Carvalho Pinto; Suzuki, Miriam Fussae; Bartolini, Paolo; Okazaki, Kayo [Instituto de Pesquisas Energeticas e Nucleares (IPEN), Sao Paulo, SP (Brazil)]. E-mail: kokazaki@ipen.br; Guimaraes, Maria Ines Calil Cury; Buchpiguel, Carlos Alberto [Sao Paulo Univ., SP (Brazil). Centro de Medicina Nuclear]. E-mail: maria.ins@hcnet.usp.br

    2005-07-01

    In nuclear medicine, the {sup 131}I is one of the most used radionuclides in thyroid disorders, for both diagnostic and therapeutic purposes. The target of the present study was to analyze the cytogenetic effects of the {sup 131}I, precede by stimulus with rec-hTSH, produced at IPEN/CNEN-SP, in an animal model by means of the chromosome aberration technique. The rec-hTSH is a glycoprotein administered in patients submitted to thyroidectomy as an alternative to the suspension of the hormone therapy for increasing the TSH level and, consequently, the {sup 131}I collection by the metastatic tissue, thus maintaining the euthyroid state. For this aim, Wistar rats were used (SPF, females, 200 g heavy), divided in 2 groups: animals treated only with {sup 131}I (G1) (11.1 MBq gastric gavage) and animals submitted to rec-hTSH-IPEN (1.2 {mu}g by intramuscular injection), 24 hours before the {sup 131}I (G2) administration. The blood samples were collected before (basal), 24 hours, 1 week and 1 month after the treatment, for cytogenetic evaluation. The cytogenetic data obtained showed an increase un the frequency of cells with chromosome aberration as well as the number of chromosome/cell aberrations, 24 hours after the {sup 131}I administration, when compared with the basal values, both for animals in group G1 and for in group G2. After 7 and 30 days of the radioiodine administration, a slight fall in the frequency of the chromosome aberrations was verified. The animals pre-treated with rec-hTSH-IPEN showed higher percentage of cells with chromosome aberration and chromosome/cell aberrations than the animals of group G1, in both de 24 hour-after administration of {sup 131}I samples and 7 day-sample, although the difference is not statistically significant (p>0,05). The results obtained allow the extrapolation for humans, in the more accurate evaluation of the biological risks involved by people exposed to the radioiodine, and also for the optimizations of a therapeutic

  20. Implementation of internal monitoring programs for workers occupationally exposed by 131I in nuclear medicine services in Brazil

    International Nuclear Information System (INIS)

    Oliveira, S.M.; Dantas, A.L.A.; Dantas, B.M.

    2017-01-01

    In nuclear medicine services (NMS), workers routinely handle radionuclides for diagnostic and therapy. This practice represents a risk of incorporation by these radionuclides. The International Atomic Energy Agency (IAEA) recommends the implementation of an internal monitoring program on workers exposed to annual effective doses greater than 1 mSv, as for example, those who handle 131 I for therapy in NMS. Currently, in Brazil, there are not enough available laboratories qualified to provide internal monitoring services to attend all possible demand of internal monitoring if it such regulation were applied by the Brazilian Nuclear Regulatory Board (CNEN). The objective of this work is to disseminate simple and inexpensive methods for in vivo routine thyroid monitoring of 131 I using equipment available in the NMS. Devices available in two public hospitals located in the city of Rio de Janeiro were calibrated for use in occupational internal monitoring. The equipment evaluated in this work presented enough sensitivity for such application, being suitable to access intakes of 131 I in the thyroid and able to estimate doses below 1 mSv. (author)

  1. Implementation of internal monitoring programs for workers occupationally exposed by {sup 131}I in nuclear medicine services in Brazil

    Energy Technology Data Exchange (ETDEWEB)

    Oliveira, S.M.; Dantas, A.L.A.; Dantas, B.M., E-mail: salomao.marques@ymail.com [Instituto de Radioproteção e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Dosimetria

    2017-07-01

    In nuclear medicine services (NMS), workers routinely handle radionuclides for diagnostic and therapy. This practice represents a risk of incorporation by these radionuclides. The International Atomic Energy Agency (IAEA) recommends the implementation of an internal monitoring program on workers exposed to annual effective doses greater than 1 mSv, as for example, those who handle {sup 131}I for therapy in NMS. Currently, in Brazil, there are not enough available laboratories qualified to provide internal monitoring services to attend all possible demand of internal monitoring if it such regulation were applied by the Brazilian Nuclear Regulatory Board (CNEN). The objective of this work is to disseminate simple and inexpensive methods for in vivo routine thyroid monitoring of {sup 131}I using equipment available in the NMS. Devices available in two public hospitals located in the city of Rio de Janeiro were calibrated for use in occupational internal monitoring. The equipment evaluated in this work presented enough sensitivity for such application, being suitable to access intakes of {sup 131}I in the thyroid and able to estimate doses below 1 mSv. (author)

  2. Vertical migration of 85Sr, 137Cs and 131I in various arable and undisturbed soils

    International Nuclear Information System (INIS)

    Palagyi, S.; Palagyiova, J.

    2002-01-01

    Vertical migration of 85 Sr, 137 Cs and 131 I in some arable and undisturbed single-contaminated soils was studied by gamma-spectrometry measurements in lysimetric laboratory conditions applying irrigation of the soil profiles with wet atmospheric precipitation for about one year (except radioiodine). A new simple exponential compartment (box) model was derived, allowing us to calculate the migration rate constants and migration rates in the individual soil layers (vertical sections) as well as the total vertical migration rate constants and total vertical migration rates of radionuclides in the bulk soil horizon. The data from the time dependence of the depth activity distribution (radionuclide concentration along the vertical soil profile) were used to test the model. The migration rate constants and migration rates were found to be affected by the contaminating radionuclides as well as by the site, type and depth of the soil. The relaxation times of the radionuclides in the soil horizons were calculated. The effects on the rate parameters of the permanent grass cover and the zeolite applied onto the arable soil surfaces were also investigated

  3. {sup 123}I and {sup 13I} purification for biomolecules labelling; Purificacao de {sup 123}I e {sup 131}I para marcacao de biomoleculas

    Energy Technology Data Exchange (ETDEWEB)

    Catanoso, Marcela Forli

    2011-07-01

    The {sup 123}I and {sup 131}I are iodine radioisotopes widely used in Nuclear Medicine. The radioisotope {sup 123}I is used in diagnosis through the SPECT technique and is routinely produced at IPEN in cyclotron through the reaction: '1{sup 24}Xe (p, 2n) '1{sup 23}Cs -> {sup 123}Xe -> {sup 123}I. The radioisotope {sup 131}I is used both in diagnosis and therapy due to its physical characteristics of decay by {beta}{sup -} and its {gamma}-ray emissions that are softened with the use of specific collimators for diagnosis. It is routinely produced at IPEN using the nuclear reactor through the indirect reaction: {sup 130}Te (n, {gamma}) ->{sup 131}Te -> {sup 131}I, irradiating compounds containing Te. The radiopharmaceuticals prepared with these radioisotopes go through rigorous quality control tests and the chemical purity of the primary radioisotopes {sup 123}I and {sup 131}I are within the permissible limits currently defined. However, the presence of some chemical contaminants can prejudice the biomolecules labeling (monoclonal antibodies and peptides), that will produce radiopharmaceuticals of first generation to the oncology area. The aim of this work was to obtain a new purification method of these radioisotopes, allowing the labeling of biomolecules and also to established a process control on those radioisotopes. The methodology was separated on 3 steps: Evaluation of '1{sup 23}I e {sup 131}I radionuclidic purity using a hyper pure germanium detector, chemical purity using ICP-OES and the retention and elution study of {sup 131}I in several absorbers to choose the most appropriate for the purification tests analyzing the behavior of the possible contaminants. The radionuclidic analyses showed the presence of Te and Co on {sup 131}I samples and Te, Tc e Co on {sup 123}I samples. The chemical purity analyses showed the presence of Al and Mo in {sup 123}I, coming from the window material of the target holder and the presence of Al and Te in {sup

  4. Model of metastatic growth valuable for radionuclide therapy

    International Nuclear Information System (INIS)

    Bernhardt, Peter; Ahlman, Haakan; Forssell-Aronsson, Eva

    2003-01-01

    The aim was to make a Monte Carlo simulation approach to estimate the distribution of tumor sizes and to study the curative potential of three candidate radionuclides for radionuclide therapy: the high-energy electron emitter 90 Y, the medium-energy electron emitter 177 Lu and the low-energy electron emitter 103m Rh. A patient with hepatocellular carcinoma with recently published serial CT data on tumor growth in the liver was used. From these data the growth of the primary tumor, and the metastatis formation rate, were estimated. Assuming the same tumor growth of the primary and all metastases and the same metastatis formation rate from both primary and metastases the metastatic size distribution was simulated for various time points. Tumor cure of the metastatic size distribution was simulated for uniform activity distribution of three radionuclides; the high-energy electron emitter 90 Y, the mean-energy electron emitter 177 Lu and the low-energy electron emitter 103m Rh. The simulation of a tumor cure was performed for various time points and tumor-to-normal tissue activity concentrations, TNC. It was demonstrated that it is important to start therapy as early as possible after diagnosis. It was of crucial importance to use an optimal radionuclide for therapy. These simulations demonstrated that 90 Y was not suitable for systemic radionuclide therapy, due to the low absorbed fraction of the emitted electrons in small tumors ( 103m Rh was slightly better than 177 Lu. For high TNC values low-energy electron emitters, e.g., 103m Rh was the best choice for tumor cure. However, the short half-life of 103m Rh (56 min) might not be optimal for therapy. Therefore, other low-energy electron emitters, or alpha emitters, should be considered for systemic targeted therapy

  5. International Comparability of 131I, 201TI and 99mTc Activity Measurements performed in Cuban Nuclear Medicine

    International Nuclear Information System (INIS)

    Oropesa, P; Serra, R; Hernandez, A.T.; Varela, C

    2006-01-01

    This paper refers about the International Comparability of 131 I, 201 TI and 99m Tc Activity Measurements performed in Cuban Nuclear Medicine. Traceability of activity measurements in nuclear medicine based in two aspects: Comparability of clinic results and the safe and effective use of drugs. A bilateral international comparison for activity measurements CIEMAT CENTIS DMR was done. 2000-2004 National Program for 99m Tc 201 TI, 131 I vial and syringe measurements in radionuclide calibrators including a simulated test for activity administration. It is employed the Cause Effect Diagram for the activity measurement result of a source in the calibrator and the statistical methods for comparing several characteristics of the obtained data. The result of the comparisons demonstrates that the measurement quality has increased from one year to another

  6. The clinical significance of measuring the thyroid 131I uptake rate to identify the type of premature hypothyroidism for hyperthyroid after 131I treatment

    International Nuclear Information System (INIS)

    Deng Bo; Chen Huaming; Zhu Tianfeng

    2001-01-01

    The 3 h thyroid 131 I uptake rate and the content of serum TT 3 , TT 4 , TSH are measured in 63 patients of premature hypothyroidism (consisting of 33 provisional hypothyroids and 30 perpetual hypothyroidism) before and after thyroxine substitutes treatment for six moths. The results show that there is obvious difference in 131 I uptake rate compared provisional hypothyroidism with perpetual hypothyroidism, and no difference in the content of serum TT 3 , TT 4 , TSH before the treatment. Compared with normal conditions, there is no difference in 131 I uptake rate of provisional hypothyroidism, but the 131 I uptake rate of perpetual hypothyroidism has obvious decrease before and after the treatment. Therefore the type of patients who suffer from premature hypothyroidism can be distinguished according to the 131 I uptake rate: if the 3 h thyroid 131 I uptake rate is normal, it is provisional hypothyroidism; if not, it is perpetual hypothyroidism

  7. Estimation of doses of ionizing radiation from patients treated with 131I

    International Nuclear Information System (INIS)

    Chaban, Y.; Matusevich, E.S.; Roziev, R.A.; Mileshin, O. A.; Shishkanov, N.G.; Klyopov, A.N.

    2001-01-01

    Radionuclide therapy currently is the principal direction of medical care delivered to population. Normative documents of the Russian Federation, that regulate radiation safety in nuclear medicine, govern the durable hospitalization of patients, undertaken the treatment with 131 I for thyroid gland disorders, such as diffuse toxic goitre and differentiated thyroid cancer. How showed the results of the processing of dosimetric information for 335 patients, at reasonable social behavior patients after radio-therapeutical procedures do not present real hazard for population and relatives. On the grounds of received data, authors came to the conclusion that, domestic norms are very strict, that can bring to rise of the cost of treatment, to reduction of the frequencies of radio-therapeutical procedures. (authors)

  8. Design and construction of a shielded process box for the production of radiopharmaceuticals labelled with 131I

    International Nuclear Information System (INIS)

    Bonetto, O.; Goso, R.; Guerrero, G.; Huala, H.E.; Logusso, N.A.; Marques, R.; Mitta, A.E.A.

    1976-07-01

    A leakproof process box, shielded with a 5 mm lead wall, for the labelling, purification, pH adjutment and dispensing of Rose Bengal 131 I, Hippuran 131 I, Diprocon 131 I, Hipaque 131 I, Bromosuphthalein 131 I, etc. is described. (author) [es

  9. The development and current status of 131I treatment for hyperthyroidism

    International Nuclear Information System (INIS)

    Wang Chunmei; Wang Xuemei

    2010-01-01

    Hyperthyroidism is an autoimmune diseasein which excessive amounts of thyroid hormones circulate in the blood. The treatments for hyperthyroidism mainly include antithyroid drugs, 131 I treatment, and surgery. 131 I had been verified as an effective, safe, simple method to treat adult and children hyperthyroidism. Current research trends of 131 I treatment mainly are problems of 131 I treatment of hyperthyroidism and its long-term security. (authors)

  10. 3D calculation of absorbed dose for 131I-targeted radiotherapy: A Monte Carlo study

    International Nuclear Information System (INIS)

    Saeedzadeh, E.; Sarkar, S.; Abbaspour Tehrani-Fard, A.; Ay, M. R.; Khosravi, H. R.; Loudos, G.

    2008-01-01

    Various methods, such as those developed by the Medical Internal Radiation Dosimetry (MIRD) Committee of the Society of Nuclear Medicine or employing dose point kernels, have been applied to the radiation dosimetry of 131 I radionuclide therapy. However, studies have not shown a strong relationship between tumour absorbed dose and its overall therapeutic response, probably due in part to inaccuracies in activity and dose estimation. In the current study, the GATE Monte Carlo computer code was used to facilitate voxel-level radiation dosimetry for organ activities measured in an. 131 I-treated thyroid cancer patient. This approach allows incorporation of the size, shape and composition of organs (in the current study, in the Zubal anthropomorphic phantom) and intra-organ and intra-tumour inhomogeneities in the activity distributions. The total activities of the tumours and their heterogeneous distributions were measured from the SPECT images to calculate the dose maps. For investigating the effect of activity distribution on dose distribution, a hypothetical homogeneous distribution of the same total activity was considered in the tumours. It was observed that the tumour mean absorbed dose rates per unit cumulated activity were 0.65 E-5 and 0.61 E-5 mGY MBq -1 s -1 for the uniform and non-uniform distributions in the tumour, respectively, which do not differ considerably. However, the dose-volume histograms (DVH) show that the tumour non-uniform activity distribution decreases the absorbed dose to portions of the tumour volume. In such a case, it can be misleading to quote the mean or maximum absorbed dose, because overall response is likely limited by the tumour volume that receives low (i.e. non-cytocidal) doses. Three-dimensional radiation dosimetry, and calculation of tumour DVHs, may lead to the derivation of clinically reliable dose-response relationships and therefore may ultimately improve treatment planning as well as response assessment for radionuclide

  11. Differentiated thyroid cancer following radioiodide 131I therapy of hyperthyroidism: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Nemec, J; Soumar, J; Zeman, V; Nahodil, V; Zamrazil, V; Smejkal, V Jr

    1978-01-01

    Differentiated (papillary) thyroid cancer was detected 17 years following radioiodide 131I treatment for toxic multinodular goiter. Twenty-one cases of thyroid cancers with previous 131I therapy for hyperthyroidism were summarized. This combination is rare compared to the incidence of thyroid cancers following external irradiation. This may be due to higher absorbed dose to thyroid in 131I treatment.

  12. Response of monitors of surface contamination to internal exposition control from {sup 131}I in the 'nuclear medicine services'; Respuesta de monitores de contaminacion superficial para el control de la exposicion interna a {sup 131}I en servicios de medicina nuclear

    Energy Technology Data Exchange (ETDEWEB)

    Puerta, Nancy; Rojo, Ana M.; Villella, Adrian; Gossio, Sebastian; Parada, Ines Gomez, E-mail: info@arn.gov.br [Autoridad Regulatoria Nuclear (ARN), Buenos Aires (Argentina); Acosta, Norma; Arenas, German, E-mail: nacosta@fuesmen.edu.ar [Fundacion Escuela de Medina Nuclear (FUESMEN), Mendoza (Argentina)

    2013-11-01

    The IAEA, in its publication RS-G-1.2, proposes individual control of workers occupationally exposed with risk of internal exposure when the potential exposure provided by incorporation leads to a value of annual committed effective dose equal to or greater than 1 mSv. Because the radionuclide {sup 131}I is the most important to control internal exposure in Nuclear Medicine Services, it is evaluated if the surface contamination monitors, commonly used in nuclear medicine centers of Argentina, would implement individual control of internal exposure to {sup 131}I. Selected detectors were calibrated with a dummy neck and thyroid with calibrated sources of {sup 131}I and {sup 133}Ba reference. For each detector is was estimated the detection efficiency for {sup 131}I and its detection limit. Each instrument was evaluated for the lowest effective dose possible to detect compromised by individual routine monitoring with different measurement intervals . We analyzed the response of each team for determining conditions that may be effective for the control of internal exposure of {sup 131}I. Finally , we conclude that the daily individual monitoring surface contamination detectors available in the Nuclear Medicine Services is feasible to implement and ensures detection of significant additions of {sup 131}I.

  13. Tumour control probability (TCP) for non-uniform activity distribution in radionuclide therapy

    International Nuclear Information System (INIS)

    Uusijaervi, Helena; Bernhardt, Peter; Forssell-Aronsson, Eva

    2008-01-01

    Non-uniform radionuclide distribution in tumours will lead to a non-uniform absorbed dose. The aim of this study was to investigate how tumour control probability (TCP) depends on the radionuclide distribution in the tumour, both macroscopically and at the subcellular level. The absorbed dose in the cell nuclei of tumours was calculated for 90 Y, 177 Lu, 103m Rh and 211 At. The radionuclides were uniformly distributed within the subcellular compartment and they were uniformly, normally or log-normally distributed among the cells in the tumour. When all cells contain the same amount of activity, the cumulated activities required for TCP = 0.99 (A-tilde TCP=0.99 ) were 1.5-2 and 2-3 times higher when the activity was distributed on the cell membrane compared to in the cell nucleus for 103m Rh and 211 At, respectively. TCP for 90 Y was not affected by different radionuclide distributions, whereas for 177 Lu, it was slightly affected when the radionuclide was in the nucleus. TCP for 103m Rh and 211 At were affected by different radionuclide distributions to a great extent when the radionuclides were in the cell nucleus and to lesser extents when the radionuclides were distributed on the cell membrane or in the cytoplasm. When the activity was distributed in the nucleus, A-tilde TCP=0.99 increased when the activity distribution became more heterogeneous for 103m Rh and 211 At, and the increase was large when the activity was normally distributed compared to log-normally distributed. When the activity was distributed on the cell membrane, A-tilde TCP=0.99 was not affected for 103m Rh and 211 At when the activity distribution became more heterogeneous. A-tilde TCP=0.99 for 90 Y and 177 Lu were not affected by different activity distributions, neither macroscopic nor subcellular

  14. Preparation of 131I-asialo-α1-acid glycoprotein

    International Nuclear Information System (INIS)

    Rijk, P.P. van

    1975-01-01

    α 1 -Acid glycoprotein (orosomucoid) was prepared from a byproduct of the ethanol plasma fractionation by means of ion-exchange procedures. Immunoelectrophoresis suggested a high degree of purity; the purified protein contained 13.5% sialic acid and 17.8% hexose. The α 1 -acid glycoprotein was modified by removal of sialic acid with neurominidase (E.C. 3.2.1.18) followed by iodination with 131 I. The purpose of the preparation, its potential use as a pharmacon for liver-function studies in nuclear medicine, is the subject of further study

  15. Treatment of hyperthyroidism: use of 131I and 125I

    International Nuclear Information System (INIS)

    Atkins, H.L.

    1977-01-01

    Factors related to late hypothyroidism following the use of 131 I for treatment of hyperthyroidism are discussed with regard to age of patient, size of dose, previous surgery, immune status, and others. Possible reasons for the post-therapeutic hypothyroidism are discussed with regard to effects of radiation on the reproductive capacity of thyroid cells, effects of radiation on blood vessels, and dose distribution of radioiodine. The following therapeutic strategies are discussed: reduction of initial dose; multiple small doses; high dose radioiodine followed by replacement therapy; the use of external beam irradiation; and the use of 125 I

  16. Effects of oral contraceptives on thyroid tests using 131I

    International Nuclear Information System (INIS)

    Carvalho, N.; Silva, W.N. da; Papaleo Netto, M.

    1973-01-01

    The effect of oral contraceptives on 131 I uptake, the depuration rate of this isotope and the PBI was studied in 24 euthyroid female patients. The dose administered was of 2.5 mg of norestinodrel and 0.05 mg of ethynil estradiol. The data were submitted to a statistical study applying analysis of variance, comparison of the means, determination of the standard deviations and the confidence interval. It is concluded that drug does affect thyroid function and that these effects may cause certain disturbances, as arterial hypertension, thrombosis, etc., in patients under prolonged contraceptive treatment [pt

  17. Treatments with radioactive iodine, 131 I. How, when and where?

    International Nuclear Information System (INIS)

    Ruiz J, A.; Gonzalez T, O.

    2006-01-01

    A great variety of approaches exists in the application of the treatments with radioactive materials, as the 131 I, but it is necessary to standardize them for the patient's benefit, because their doctor doesn't always know the principle that it bases this therapy, called metabolic therapy or radioiodine therapy (RYT). In this work the experience that was acquired by more of 50 years of RYT management in the Thyroid and Nuclear Medicine Clinic in patients with thyroid pathologies is informed, so that their management fulfills its function and it was carried out inside the corresponding juridical frame and the physicochemical and endocrinological principles that should take implicit. (Author)

  18. Evaluation of irradiation in patient's environment receiving 131I therapy

    International Nuclear Information System (INIS)

    Husar, J.; Fueriova, A.; Borovicova, F.

    1998-01-01

    This article describes measurements made in the bed station of Clinic of Nuclear Medicine in St. Elizabeth Oncological Institute in Bratislava. There are treated thyroid cancer and thyrotoxicosis with the use of 131 I. The aim of the measurements was to determine the possibility of the ambulation treatment of thyrotoxicosis or the possibility of shortening of the patient;s stay in the bed station that the effective dose would not be exceeded suggestions according to the publication of EURATOM. The measurements were made also with thyroid cancer patients but owing to clinical reasons the ambulation treating in this case is not permissible. Therefore this article does not describe the results of these measurements.The effective dose rates were measured in 0.25 m; 0.5 m; 1 m and 2 m distances from the patient's thyroid so the effective dose in the patient's surroundings could be determined. To the present time the results of effective dose rates measurements for 17 patients were evaluated by described way. The age of the patients was from 41 to 82 years, the administered quantity of 131 I was from 259 to 481 MBq, in fractions 37 MBq, 74 MBq, or 111 MBq. The calculated effective half-life of 131 I excretion from the patients body is crucial for the length of patient's necessary staying in the bed station, were from 4.2 days to 8 days. This great extend of values is given by by the different clinical parameters of the treated patients. After the analyse of them can be said that the effective half-life increases, when the patient is elder, has greater mass of thyroid and the accumulation is higher. At the present time authors don't suggest using the ambulation treatment of thyrotoxicosis by 131 I. For discharging the patient from the hospital authors suggest to think criteria according to the model of behaviour D with the effective dose limit 0.5 mSv. For the households with children up to 2 years and/or pregnant women according to the model B with effective dose limit 0

  19. Development of methodology for evaluation of {sup 99m}Tc and {sup 131}I incorporated activities during lactation; Desenvolvimento de metodologia para avaliacao da atividade de {sup 99m}Tc e {sup 131}I em lactantes

    Energy Technology Data Exchange (ETDEWEB)

    Santos, L. [Universidade Federal do Rio de Janeiro (IF/UFRJ), RJ (Brazil). Inst. de Fisica; Dantas, A.L.A.; Mesquita, S.A. [Universidade Federal do Rio de Janeiro (IF/UFRJ), RJ (Brazil). Inst. de Fisica; Oliveira, S.M.V., E-mail: adantas@ird.gov.br, E-mail: silvia@ird.gov.br [Universidade Federal do Rio de Janeiro (IF/UFRJ), RJ (Brazil). Inst. de Fisica; Instituto de Radioprotecao e Dosimetria (IRD/CNEN-RJ), Rio de Janeiro, RJ (Brazil). Div. de Dosimetria

    2012-07-01

    Internal contamination of babies may occur for milk ingestion or inhalation of mothers occupationally exposed to ionizing radiation with possible incorporation or mothers submitted to medical exposures during lactation. Radionuclide concentrations in the mother's milk may cause organ absorbed doses in the babies proportionally to the breast volumes. Milk analysis allow to determine activities ingested by the babies by determining the peak of mother's milk considering the decrease of the activity rate and the milk activities drunk at different time intervals. The work had the aim to develop simulators and methodology to evaluate {sup 99m}Tc and {sup 131}I in lactation, in the following steps: to prepare standard solution of contaminated milk separately with {sup 99m}Tc and {sup 131}I; to build four breast simulators (600 g and 800 g) and respective calibration for two geometries (breast and whole-body) in the Whole-Body Counter Unit in Instituto de Radioprotecao e Dosimetria. The results demonstrated the system efficiency to determine {sup 99m}Tc and {sup 131}I activities in breasts during the lactation period. The methodology for positioning in the 'breast geometry' seemed to be more efficient than the 'whole-body geometry' for different breast volumes. The experiment allows achieving better evaluation of internal dosimetry of mothers and their young children. (author)

  20. A Comparative Study of 131I-Hippuran Renogram, 131I-Hippuran Urinary Excretion Test and Intravenous Pyelogram in Obstructive Uropathy due to Cancerous Invasion

    International Nuclear Information System (INIS)

    Park, Kee Bok; Rhee, Chong Heon; Hong, Chang Gi; Park, Soo Seong; Koh, Chang Soon

    1968-01-01

    A comparative study of 131 I-hippuran renogram, 131 I-hippuran excretion test and intravenous pyelogram were performed in 61 cases of gynecological cancer. The following were the results: 1) Among 40 cases of cervix cancer showing normal excretory urography 7 cases (17.5%) were found to have unilateral or bilateral delayed excretory pattern on 131 I-hippuran renogram and on the contrary only 2 cases (5.7%) showed a mild caliectatic change on excretory urography among 35 cases of gynecological cancer showing normal pattern of 131 I-hippuran renogram. 2) In the group showing unilateral of bilateral delayed excretory pattern of 131 I-hippuran renogram there was a reduction of 131 I-hippuran excretion in the first 20 minutes, but there was no significant difference of 131 I-hippuran excretion in 60 minutes compared with that of normal renogram group. 3) In the group showing unilateral non-functioning pattern of 131 I-hippuran renogram in one side and normal pattern in the other side there was found to be no difference in 131 I-hippuran excretion amount compared with that of normal renogram group. 4) It was evident from these experimental study that 131 I-hippuran renogram was considered as a good examination method for the evaluation of obstructive uropathy, and if one side kidney was intact it might compensate for the other diseased kidney so far as to renal excretory function. It was also shown that the more severe the cancerous spread in the pelvic wall the more changes on 131 I-hippuran renogram.