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Sample records for 177lu radioisotope separation

  1. Specific radioactivity of neutron induced radioisotopes: assessment methods and application for medically useful 177Lu production as a case.

    PubMed

    Le, Van So

    2011-01-19

    The conventional reaction yield evaluation for radioisotope production is not sufficient to set up the optimal conditions for producing radionuclide products of the desired radiochemical quality. Alternatively, the specific radioactivity (SA) assessment, dealing with the relationship between the affecting factors and the inherent properties of the target and impurities, offers a way to optimally perform the irradiation for production of the best quality radioisotopes for various applications, especially for targeting radiopharmaceutical preparation. Neutron-capture characteristics, target impurity, side nuclear reactions, target burn-up and post-irradiation processing/cooling time are the main parameters affecting the SA of the radioisotope product. These parameters have been incorporated into the format of mathematical equations for the reaction yield and SA assessment. As a method demonstration, the SA assessment of 177Lu produced based on two different reactions, 176Lu (n,γ)177Lu and 176Yb (n,γ) 177Yb (β- decay) 177Lu, were performed. The irradiation time required for achieving a maximum yield and maximum SA value was evaluated for production based on the 176Lu (n,γ)177Lu reaction. The effect of several factors (such as elemental Lu and isotopic impurities) on the 177Lu SA degradation was evaluated for production based on the 176Yb (n,γ) 177Yb (β- decay) 177Lu reaction. The method of SA assessment of a mixture of several radioactive sources was developed for the radioisotope produced in a reactor from different targets.

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

    NASA Astrophysics Data System (ADS)

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

    2016-06-01

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

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

    NASA Astrophysics Data System (ADS)

    Danagulyan, A. S.; Hovhannisyan, G. H.; Bakhshiyan, T. M.; Avagyan, R. H.; Avetisyan, A. E.; Kerobyan, I. A.; Dallakyan, R. K.

    2015-06-01

    The possibility of the photonuclear production of radioisotopes 111In, 117 m Sn, 124Sb, and 177Lu is discussed. Reaction yields were measured by the gamma-activation method. The enriched tin isotopes 112, 118Sn and Te and HfO2 of natural isotopic composition were used as targets. The targets were irradiated at the linear electron accelerator of Alikhanian National Science Laboratory (Yerevan) at the energy of 40 MeV. The experimental results obtained in this way reveal that the yield and purity of radioisotopes 111In and 117 mSn are acceptable for their production via photonuclear reactions. Reactions proceeding on targets from Te and HfO2 of natural isotopic composition and leading to the formation of 124Sb and 177Lu have small yields and are hardly appropriate for the photoproduction of these radioisotopes even in the case of enriched targets.

  4. Half-life measurement of the medical radioisotope 177Lu produced from the 176Yb(n,γ) reaction

    NASA Astrophysics Data System (ADS)

    Ferreira, K. M.; Collins, S. M.; Fenwick, A. J.

    2017-09-01

    177Lu is a medium energy beta-emitter commonly used in Nuclear Medicine for radiotherapeutic applications. In this work, the half-life of 177Lu has been measured using a re-entrant ionisation chamber over a period of 82 days (approximately 12 half-lives). Unlike the majority of previous studies, the material used in this work was produced via the 176Yb(n,γ)177Yb reaction followed by the β-decay to 177Lu, producing insignificant quantities of 177mLu. This has resulted in the most precise half-life measurement of 177Lu to date. A half-life of 6.6430 (11) days has been determined. This value is in statistical agreement with the currently recommended half-life of 6.6463 (15) days (z-score = 1.8).

  5. Indirect Production of No Carrier Added (NCA) (177)Lu from Irradiation of Enriched (176)Yb: Options for Ytterbium/Lutetium Separation.

    PubMed

    Dash, Ashutosh; Chakravarty, Rubel; Knapp, Furn F Russ; Pillai, Ambikalmajan M R

    2015-01-01

    This article presents a concise review of the production of no-carrier-added (NCA) (177)Lu by the 'indirect' route by irradiating ytterbium-176 ((176)Yb)-enriched targets. The success of this production method depends on the ability to separate the microscopic amounts of NCA (177)Lu from bulk irradiated ytterbium targets. The presence of Yb(+3) from the target in the final processed (177)Lu will adversely affect the quality of (177)Lu by decreasing the specific activity and competing with Lu(+3) complexation since ytterbium will follow the same coordination chemistry. Ytterbium and lutetium are adjacent members of the lanthanide family with very similar chemical properties which makes the separation of one from the other a challenging task. This review provides a summary of the methods developed for the separation and purification of NCA (177)Lu from neutron irradiated (176)Yb-enriched targets, a critical assessment of recent developments and a discussion of the current status of this (177)Lu production method.

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

    SciTech Connect

    Danagulyan, A. S.; Hovhannisyan, G. H. Bakhshiyan, T. M.; Avagyan, R. H.; Avetisyan, A. E.; Kerobyan, I. A.; Dallakyan, R. K.

    2015-06-15

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

  7. Method for preparing high specific activity 177Lu

    DOEpatents

    Mirzadeh, Saed; Du, Miting; Beets, Arnold L.; Knapp, Jr., Furn F.

    2004-04-06

    A method of separating lutetium from a solution containing Lu and Yb, particularly reactor-produced .sup.177 Lu and .sup.177 Yb, includes the steps of: providing a chromatographic separation apparatus containing LN resin; loading the apparatus with a solution containing Lu and Yb; and eluting the apparatus to chromatographically separate the Lu and the Yb in order to produce high-specific-activity .sup.177 Yb.

  8. Quantitative SPECT/CT reconstruction for 177Lu and 177Lu/90Y targeted radionuclide therapies

    NASA Astrophysics Data System (ADS)

    Shcherbinin, S.; Piwowarska-Bilska, H.; Celler, A.; Birkenfeld, B.

    2012-09-01

    We investigated the quantitative accuracy of SPECT/CT imaging studies as would be performed before and after targeted radionuclide therapy (TRT) using phantom experiments with (i) 99mTc, (ii) 177Lu and (iii) 90Y/177Lu. While the experiment with 99mTc imitated a diagnostic scan, the experiments with 177Lu and 90Y/177Lu modeled post-therapy acquisitions. At the next stage, we reconstructed images from pre- and post-therapy patient studies. The data were first reconstructed using two methods with limited corrections for the physics effects. Then, to generate quantitatively accurate absolute activity distributions, we applied a hybrid (model-based and window-based) reconstruction strategy where some of the physics effects were accurately modeled while corrections for other effects were empirical and based on information obtained from the projection data. The accuracies of absolute activity recovered by the hybrid method from the six phantom experiments were very similar to each other and acceptable for potential use in TRT. When measured in identical regions of interest, the 99mTc activity was reconstructed with errors ranging between -3.3% and 2.9%, while the 177Lu activity was reconstructed from experiments with 177Lu and 90Y/177Lu with errors ranging between -1.6% and 1.6%. The reconstruction algorithms with limited corrections led to larger and case-specific errors as might have been expected. From a clinical prospective, our results showed that physics-based reconstructions improved resolution of images corresponding to both diagnostic scans with 99mTc and post-therapy scans with 177Lu. Our analysis of patient study demonstrated that lack of corrections led to overestimation of activities in organs and tumor by 29-39% for the diagnostic scan with 99mTc and by 105-218% for post-therapy scan with 177Lu.

  9. Synthesis and Evaluation of a New Bifunctional NETA Chelate for Molecular Targeted Radiotherapy Using 90Y or 177Lu

    PubMed Central

    Kang, Chi Soo; Chen, Yunwei; Lee, Hyunbeom; Liu, Dijie; Sun, Xiang; Kweon, Junghun; Lewis, Michael R.; Chong, Hyun-Soon

    2015-01-01

    Introduction Therapeutic potential of β-emitting cytotoxic radionuclides 90Y and 177Lu have been demonstrated in numerous preclinical and clinical trials. A bifunctional chelate that can effectively complex with the radioisotopes is a critical component for molecular targeted radiotherapy 90Y and 177Lu. A new bifunctional chelate 5p-C-NETA with a relatively long alkyl spacer between the chelating backbone and the functional unit for conjugation to a tumor targeting moiety was synthesized. 5p-C-NETA was conjugated to a model targeting moiety, a cyclic Arg-Gly-Asp-D-Tyr-Lys (RGDyK) peptide binding integrin αvβ3 protein overexpressed on various cancers. 5p-C-NETA was conjugated to c(RGDyK) peptide and evaluated for potential use in molecular targeted radiotherapy of 90Y and 177Lu. Methods 5p-C-NETA conjugated with c(RGDyK) was evaluated in vitro for radiolabeling, serum stability, binding affinity, and the result of the in vitro studies of 5p-C-NETA-c(RGDyK) was compared to that of 3p-CNETA-c(RGDyK). 177Lu-5p-C-NETA-c(RGDyK) was further evaluated for in vivo biodistribution using gliobastoma bearing mice. Result The new chelate rapidly and tightly bound to a cytotoxic radioisotope for cancer therapy, 90Y or 177Lu with excellent radiolabeling efficiency and maximum specific activity under mild condition (>99%, RT, <1 min). 90Y- and 177Lu-radiolabeled complexes of the new chelator remained stable in human serum without any loss of the radiolanthanide for 14 days. Introduction of the tumor targeting RGD moiety to the new chelator made little impact on complexation kinetics and stability with 90Y or 177Lu. 177Lu-radiolabeled 5p-C-NETA-c(RGDyK) conjugate was shown to target tumors in mice and produced a favorable in vivo stability profile. Conclusion The results of in vitro and in vivo evaluation suggest that 5p-C-NETA is an effective bifunctional chelate of 90Y and 177Lu that can be applied for generation of versatile molecular targeted radiopharmaceuticals. PMID

  10. Synthesis and evaluation of a new bifunctional NETA chelate for molecular targeted radiotherapy using(90)Y or(177)Lu.

    PubMed

    Kang, Chi Soo; Chen, Yunwei; Lee, Hyunbeom; Liu, Dijie; Sun, Xiang; Kweon, Junghun; Lewis, Michael R; Chong, Hyun-Soon

    2015-03-01

    Therapeutic potential of β-emitting cytotoxic radionuclides (90)Y and (177)Lu has been demonstrated in numerous preclinical and clinical trials. A bifunctional chelate that can effectively complex with the radioisotopes is a critical component for molecular targeted radiotherapy (90)Y and (177)Lu. A new bifunctional chelate 5p-C-NETA with a relatively long alkyl spacer between the chelating backbone and the functional unit for conjugation to a tumor targeting moiety was synthesized. 5p-C-NETA was conjugated to a model targeting moiety, a cyclic Arg-Gly-Asp-D-Tyr-Lys (RGDyK) peptide binding integrin αvβ3 protein overexpressed on various cancers. 5p-C-NETA was conjugated to c(RGDyK) peptide and evaluated for potential use in molecular targeted radiotherapy of (90)Y and (177)Lu. 5p-C-NETA conjugated with c(RGDyK) was evaluated in vitro for radiolabeling, serum stability, binding affinity, and the result of the in vitro studies of 5p-C-NETA-c(RGDyK) was compared to that of 3p-C-NETA-c(RGDyK). (177)Lu-5p-C-NETA-c(RGDyK) was further evaluated for in vivo biodistribution using gliobastoma bearing mice. The new chelate rapidly and tightly bound to a cytotoxic radioisotope for cancer therapy, (90)Y or (177)Lu with excellent radiolabeling efficiency and maximum specific activity under mild condition (>99%, RT, <1 min). (90)Y- and (177)Lu-radiolabeled complexes of the new chelator remained stable in human serum without any loss of the radiolanthanide for 14 days. Introduction of the tumor targeting RGD moiety to the new chelator made little impact on complexation kinetics and stability with (90)Y or (177)Lu. (177)Lu-radiolabeled 5p-C-NETA-c(RGDyK) conjugate was shown to target tumors in mice and produced a favorable in vivo stability profile. The results of in vitro and in vivo evaluation suggest that 5p-C-NETA is an effective bifunctional chelate of (90)Y and (177)Lu that can be applied for generation of versatile molecular targeted radiopharmaceuticals. Copyright © 2014

  11. H4octapa-Trastuzumab: Versatile Acyclic Chelate System for 111In and 177Lu Imaging and Therapy

    PubMed Central

    Price, Eric W.; Zeglis, Brian M.; Cawthray, Jacqueline F.; Ramogida, Caterina F.; Ramos, Nicholas

    2013-01-01

    A bifunctional derivative of the versatile acyclic chelator H4octapa, p-SCNBn- H4octapa, has been synthesized for the first time. The chelator was conjugated to the HER2/neu-targeting antibody trastuzumab and labeled in high radiochemical purity and specific activity with the radioisotopes 111In and 177Lu. The in vivo behavior of the resulting radioimmunoconjugates was investigated in mice bearing ovarian cancer xenografts and compared to analogous radioimmunoconjugates employing the ubiquitous chelator DOTA. The H4octapa-trastuzumab conjugates displayed faster radiolabeling kinetics with more reproducible yields under milder conditions (15 min, RT, ~94–95%) than those based on DOTA-trastuzumab (60 min, 37 °C ~50–88%). Further, antibody integrity was better preserved in the 111In- and 177Lu-octapatrastuzumab constructs, with immunoreactive fractions of 0.99 for each compared to 0.93–0.95 for 111In- and 177Lu-DOTA-trastuzumab. These results translated to improved in vivo biodistribution profiles and SPECT imaging results for 111In- and 177Lu-octapa-trastuzumab compared to 111In- and 177Lu-DOTA-trastuzumab, with increased tumor uptake and higher tumor-to-tissue activity ratios. PMID:23901833

  12. Synthesis and comparative biological evaluation of bifunctional ligands for radiotherapy applications of (90)Y and (177)Lu.

    PubMed

    Chong, Hyun-Soon; Sun, Xiang; Chen, Yunwei; Sin, Inseok; Kang, Chi Soo; Lewis, Michael R; Liu, Dijie; Ruthengael, Varyanna C; Zhong, Yongliang; Wu, Ningjie; Song, Hyun A

    2015-03-01

    Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope ((90)Y) that was approved for radioimmunotherapy (RIT) of B-cell non-Hodgkin's lymphoma. A bifunctional ligand that displays favorable complexation kinetics and in vivo stability is required for effective RIT. New bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA for potential use in RIT were efficiently prepared by the synthetic route based on regiospecific ring opening of aziridinium ions with prealkylated triaza- or tetraaza-backboned macrocycles. The new bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA along with the known bimodal ligands 3p-C-NETA and 3p-C-DEPA were comparatively evaluated for potential use in targeted radiotherapy using β-emitting radionuclides (90)Y and (177)Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with (90)Y and (177)Lu, and the corresponding (90)Y or (177)Lu-radiolabeled complexes were studied for in vitro stability in human serum and in vivo biodistribution in mice. The results of the comparative complexation kinetic and stability studies indicate that size of macrocyclic cavity, ligand denticity, and bimodality of donor groups have a substantial impact on complexation of the bifunctional ligands with the radiolanthanides. The new promising bifunctional chelates in the DE4TA and NE3TA series were rapid in binding (90)Y and (177)Lu, and the corresponding (90)Y- and (177)Lu-radiolabeled complexes remained inert in human serum or in mice. The in vitro and in vivo data show that 3p-C-DE4TA and 3p-C-NE3TA are promising bifunctional ligands for targeted radiotherapy applications of (90)Y and (177)Lu. Copyright © 2014 Elsevier Ltd. All rights reserved.

  13. Synthesis and Comparative Biological Evalution of Bifunctional Ligands for Radiotherapy Applications of 90Y and 177Lu

    PubMed Central

    Chong, Hyun-Soon; Sun, Xiang; Chen, Yunwei; Sin, Inseok; Kang, Chi Soo; Lewis, Michael R.; Liu, Dijie; Ruthengael, Varyanna C.; Zhong, Yongliang; Wu, Ningjie; Song, Hyun A

    2015-01-01

    Zevalin® is an antibody-drug conjugate radiolabeled with a cytotoxic radioisotope (90Y) that was approved for radioimmunotherapy (RIT) of B-cell non-Hodgkin’s lymphoma. A bifunctional ligand that displays favorable complexation kinetics and in vivo stability is required for effective RIT. New bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA for potential use in RIT were efficiently prepared by the synthetic route based on regiospecific ring opening of aziridinium ions with prealkylated triaza- or tetraaza-backboned macrocycles. The new bifunctional ligands 3p-C-DE4TA and 3p-C-NE3TA along with the known bimodal ligands 3p-C-NETA and 3p-C-DEPA were comparatively evaluated for potential use in targeted radiotherapy using β-emitting radionuclides 90Y and 177Lu. The bifunctional ligands were evaluated for radiolabeling kinetics with 90Y and 177Lu, and the corresponding 90Y or 177Lu-radiolabeled complexes were studied for in vitro stability in human serum and in vivo biodistribution in mice. The results of the comparative complexation kinetic and stability studies indicate that size of macrocyclic cavity, ligand denticity, and bimodality of donor groups have a substantial impact on complexation of the bifunctional ligands with the radiolanthanides. The new promising bifunctional chelates in the DE4TA and NE3TA series were rapid in binding 90Y and 177Lu, and the corresponding 90Y- and 177Lu-radiolabeled complexes remained inert in human serum or in mice. The in vitro and in vivo data show that 3p-C-DE4TA and 3p-C-NE3TA are promising bifunctional ligands for targeted radiotherapy applications of 90Y and 177Lu. PMID:25648683

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

    PubMed Central

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

    2015-01-01

    Over the past few decades, several bone-seeking radiopharmaceuticals including various bisphosphonate ligands and β-emitting radionuclides have been developed for bone pain palliation. Recently, 177Lu was successfully labeled with zoledronic acid (177Lu-ZLD) as a new generation potential bisphosphonate and demonstrated significant accumulation in bone tissue. In this work, the absorbed dose to each organ of human for 177Lu-ZLD and 177Lu-ethylenediaminetetramethylene phosphonic acid (177Lu-EDTMP;as the only clinically bone pain palliation agent) was investigated based on biodistribution data in rats by medical internal radiation dosimetry (MIRD) method. 177Lu-ZLD and 177Lu-EDTMP were prepared in high radiochemical purity (>99%, instant thin layer chromatography (ITLC)) at the optimized condition. The biodistribution of the complexes demonstrated fast blood clearance and major accumulation in the bone tissue. The highest absorbed dose for both 177Lu-ZLD and 177Lu-EDTMP is observed in trabecular bone surface with 12.173 and 10.019 mSv/MBq, respectively. The results showed that 177Lu-ZLD has better characteristics compared to 177Lu-EDTMP and can be a good candidate for bone pain palliation. PMID:26170557

  15. Characteristics of Bremsstrahlung emissions of (177)Lu, (188)Re, and (90)Y for SPECT/CT quantification in radionuclide therapy.

    PubMed

    Uribe, Carlos F; Esquinas, Pedro L; Gonzalez, Marjorie; Celler, Anna

    2016-05-01

    Beta particles emitted by radioisotopes used in targeted radionuclide therapies (TRT) create Bremsstrahlung (BRS) which may affect SPECT quantification when imaging these isotopes. The purpose of the current study was to investigate the characteristics of Bremsstrahlung produced in tissue by three β-emitting radioisotopes used in TRT. Monte Carlo simulations of (177)Lu, (188)Re, and (90)Y sources placed in water filled cylinders were performed. BRS yields, mean energies and energy spectra for (a) all photons generated in the decays, (b) photons that were not absorbed and leave the cylinder, and (c) photons detected by the camera were analyzed. Next, the results of simulations were compared with those from experiments performed on a clinical SPECT camera using same acquisition conditions and phantom configurations as in simulations. Simulations reproduced relatively well the shapes of the measured spectra, except for (90)Y which showed an overestimation in the low energy range. Detailed analysis of the results allowed us to suggest best collimators and imaging conditions for each of the investigated isotopes. Finally, our simulations confirmed that the BRS contribution to the energy spectra in quantitative imaging of (177)Lu and (188)Re could be ignored. For (177)Lu and (188)Re, BRS contributes only marginally to the total spectra recorded by the camera. Our analysis shows that MELP and HE collimators are the best for imaging these two isotopes. For (90)Y, HE collimator should be used. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  16. (177)Lu-PSMA Radioligand Therapy for Prostate Cancer.

    PubMed

    Fendler, Wolfgang P; Rahbar, Kambiz; Herrmann, Ken; Kratochwil, Clemens; Eiber, Matthias

    2017-08-01

    (177)Lu-prostate-specific membrane antigen (PSMA) radioligand therapy (RLT) using inhibitors of PSMA is a novel therapeutic option in patients with metastatic castration-resistant prostate cancer. The current literature suggests that this therapy is well tolerated and effective. On the basis of clinical need and current evidence, the therapy is being implemented in a growing number of centers worldwide. Here, we review important aspects of (177)Lu-PSMA RLT, including patient stratification, the therapy protocol, concomitant medication, and follow-up, to inform medical staff involved in the RLT and care of patients with metastatic castration-resistant prostate cancer. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

  17. 177Lu-labeled Gold Nanoparticles for Radiation Therapy of Locally Advanced Breast Cancer

    NASA Astrophysics Data System (ADS)

    Yook, Simmyung

    Locally advanced breast cancer (LABC) occurs in about 10-15% of patients diagnosed with breast cancer (BC) and 30% of these patients have triple negative breast cancer (TNBC) that are often epidermal growth factor receptor (EGFR)-positive. The goal of the proposed research was design and evaluate preclinically a novel radiation nanomedicine for LABC composed of EGFR-targeted gold nanoparticles (AuNP) by covalently conjugating panitumumab and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) complexing 177Lu incorporated into a metal-chelating polymer (MCP) (177 Lu-T-AuNP) which could be used as a neoadjuvant treatment to improve the outcome of patients with LABC. 177Lu-T-AuNP were efficiently internalized by EGFR-positive BC cells and were significantly more effective than 177Lu-labeled and non-targeted (NT)-AuNP for killing these cells. For radiation treatment of EGFR-positive tumours, both 177Lu-T-AuNP and 177Lu-NT-AuNP were intratumourally (i.t.) injected into athymic mice with MDA-MB-468 BC xenografts for comparison. Biodistribution studies showed that 177Lu-T-AuNPs exhibited 2-fold higher tumour retention than 177Lu-NT-AuNPs following i.t. injection at 48 h p.i. Both forms of radiolabeled AuNP were highly effective for inhibiting tumour growth without normal organ toxicity due to local tumour retention of both form of AuNP. To minimize the displacement of 177Lu-labeled MCP from AuNP, polyethylene glycol (PEG) ligands presenting a disulfide [ 177Lu-DOTA-PEG-ortho-pyridyl disulfide (OPSS)], a lipoic acid (LA) [177Lu-DOTA-PEG-lipoic acid (LA)] or multi-LA [PEG- pGlu(177Lu-DOTA)8-LA4] for multivalent binding were synthesized and the stability of MCP-AuNP complexes determined. In vitro challenge study with thiol-containing molecules or human plasma, PEG-pGlu(DOTA)8-LA4-AuNP were most stable. In whole body elimination study, elimination of radioactivity due to displacement of 177Lu-MCP from AuNP in mice injected with 177Lu-DOTA-PEG-OPSS-AuNP was more

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

    PubMed Central

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

    2013-01-01

    The biodistribution of the anti-CD37 radioimmunoconjugate 177Lu-tetraxetan-tetulomab (177Lu-DOTA-HH1) was evaluated. Biodistribution of 177Lu-tetraxetan-tetulomab was compared with 177Lu-tetraxetan-rituximab and free 177Lu in nude mice implanted with Daudi lymphoma xenografts. The data showed that 177Lu-tetulomab had a relevant stability and tumor targeting properties in the human lymphoma model. The half-life of 177Lu allowed significant tumor to normal tissue ratios to be obtained indicating that 177Lu-tetraxetan-tetulomab could be suitable for clinical testing. The biological and effective half-life in blood was higher for 177Lu-tetraxetan-tetulomab than for 177Lu-tetraxetan-rituximab. The biodistribution of 177Lu-tetraxetan-tetulomab did not change significantly when the protein dose was varied from 0.01 to 1 mg/kg. Dosimetry calculations showed that the absorbed radiation doses to normal tissues and tumor in mice were not significantly different for 177Lu-tetraxetan-tetuloma b and 177Lu-tetraxetan-rituximab. The absorbed radiation doses were extrapolated to human absorbed radiation doses. These extrapolated absorbed radiation doses to normal tissues for 177Lu-tetraxetan-tetulomab at an injection of 40 MBq/kg were significantly lower than the absorbed radiation doses for 15 MBq/kg Zevalin, suggesting that higher tumor radiation dose can be reached with 177Lu-tetraxetan-tetulomab in the clinic. PMID:23256748

  19. Consequences of meta-stable (177m)Lu admixture in (177)Lu for patient dosimetry.

    PubMed

    Konijnenberg, Mark W

    2015-01-01

    Lutetium-177 ((177)Lu) is a rare earth metal in the lanthanides series which decays by beta emission with a half life of 6.647 days to three excited states and the ground state of (177)Hf. When (177)Lu is produced by neutron capture in (176)Lu, inevitably an admixture is formed of the long-lived isomer (177)mLu. As its half-life of 160.4 days is so much longer than that of (177)Lu, concerns are raised on its possible enhancement in radiation dose to the patient treated with (177)Lu-DOTA-octreotate. This report evaluates this possible enhancement of the absorbed dose, based on the published pharmacokinetic profile of (177)Lu-DOTA-octreotate and assuming an admixture of 1 kBq (177)mLu /MBq (177)Lu (0.1%).

  20. Preparation of clinical-scale (177) Lu-Rituximab: Optimization of protocols for conjugation, radiolabeling and freeze-dried kit formulation.

    PubMed

    Guleria, Mohini; Das, Tapas; Kumar, Chandan; Amirdhanayagam, Jeyachitra; Sarma, Haladhar D; Banerjee, Sharmila

    2017-02-08

    Rituximab is a monoclonal chimeric antibody which has been approved by US FDA for immunotherapy of Non-Hodgkins' lymphoma (NHL). Bexxar and Zevalin are the two other approved radiolabeled antibodies for radioimmunotherapy of NHL; however the fact that they are of murine origin reduces their treatment efficacy. To circumvent this, efforts have been made to radiolabel Rituximab with various therapeutic radioisotopes. In the present study, an effort has been made to optimize the conjugation (BFCA and antibody) and radiolabeling procedures for the preparation of clinical-scale (177) Lu-labeled Rituximab. An attempt was also made to prepare the freeze-dried Rituximab kit for the easy and convenient clinical translation of the agent. Clinical-scale (177) Lu-Rituximab (40 mCi, 1.48 GBq) was prepared with >95% radiochemical purity using the kit. Biological evaluation of (177) Lu-Rituximab was carried out by in-vitro cell binding studies in Raji cell lines, which showed satisfactory binding at 4 and 37 °C. Pharmacokinetic behaviour of the agent, evaluated by biodistribution studies in normal Swiss mice, revealed high blood and liver uptake at the initial time points; although it exhibited slow and gradual clearance with time. The study indicates that clinical-scale (177) Lu-Rituximab could be conveniently formulated using the methodology described in the present article.

  1. Optimization of irradiation conditions for {sup 177}Lu production at the LVR-15 research reactor

    SciTech Connect

    Lahodova, Z.; Viererbl, L.; Klupak, V.; Srank, J.

    2012-07-01

    The use of lutetium in medicine has been increasing over the last few years. The {sup 177}Lu radionuclide is commercially available for research and test purposes as a diagnostic and radiotherapy agent in the treatment of several malignant tumours. The yield of {sup 177}Lu from the {sup 176}Lu(n,{gamma}){sup 177}Lu nuclear reaction depends significantly on the thermal neutron fluence rate. The capture cross-sections of both reaction {sup 176}Lu(n,{gamma}){sup 177}Lu and reaction {sup 177}Lu(n,{gamma}){sup 178}Lu are very high. Therefore a burn-up of target and product nuclides should be taken into account when calculating {sup 177}Lu activity. The maximum irradiation time, when the activity of the {sup 177}Lu radionuclide begins to decline, was found for different fluence rates. Two vertical irradiation channels at the LVR-15 nuclear research reactor were compared in order to choose the channel with better irradiation conditions, such as a higher thermal neutron fluence rate in the irradiation volume. In this experiment, lutetium was irradiated in a titanium capsule. The influence of the Ti capsule on the neutron spectrum was monitored using activation detectors. The choice of detectors was based on requirements for irradiation time and accurate determination of thermal neutrons. The following activation detectors were selected for measurement of the neutron spectrum: Ti, Fe, Ni, Co, Ag and W. (authors)

  2. Tumoral fibrosis effect on the radiation absorbed dose of (177)Lu-Tyr(3)-octreotate and (177)Lu-Tyr(3)-octreotate conjugated to gold nanoparticles.

    PubMed

    Azorín-Vega, E P; Zambrano-Ramírez, O D; Rojas-Calderón, E L; Ocampo-García, B E; Ferro-Flores, G

    2015-06-01

    The aim of this work was to evaluate the tumoral fibrosis effect on the radiation absorbed dose of the radiopharmaceuticals (177)Lu-Tyr(3)-octreotate (monomeric) and (177)Lu-Tyr(3)-octreotate-gold nanoparticles (multimeric) using an experimental HeLa cells tumoral model and the Monte Carlo PENELOPE code. Experimental and computer micro-environment models with or without fibrosis were constructed. Results showed that fibrosis increases up to 33% the tumor radiation absorbed dose, although the major effect on the dose was produced by the type of radiopharmaceutical (112Gy-multimeric vs. 43Gy-monomeric).

  3. Thermal neutron capture cross section for the K isomer {sup 177}Lu{sup m}

    SciTech Connect

    Belier, G.; Roig, O.; Daugas, J.-M.; Giarmana, O.; Meot, V.; Letourneau, A.; Marie, F.; Foucher, Y.; Aupiais, J.; Abt, D.; Jutier, Ch.; Le Petit, G.; Bettoni, C.; Gaudry, A.; Veyssiere, Ch.; Barat, E.; Dautremer, T.; Trama, J.-Ch.

    2006-01-15

    The thermal neutron radiative capture cross section for the K isomeric state in {sup 177}Lu has been measured for the first time. Several {sup 177}Lu{sup m} targets have been prepared and irradiated in various neutron fluxes at the Lauee Langevin Institute in Grenoble and at the CEA reactors OSIRIS and ORPHEE in Saclay. The method consists of measuring the {sup 178}Lu activity by {gamma}-ray spectroscopy. The values obtained in four different neutron spectra have been used to calculate the resonance integral of the radiative capture cross section for {sup 177}Lu{sup m}. In addition, an indirect method leads to the determination of the {sup 177}Lu{sup g} neutron radiative capture cross section.

  4. A potencial theranostic agent for EGF-R expression tumors: (177)Lu-DOTA-nimotuzumab.

    PubMed

    Calzada, Victoria; Zhang, Xiuli; Fernandez, Marcelo; Diaz-Miqueli, Arlhee; Iznaga-Escobar, Normando; Deutscher, Susan L; Balter, Henia; Quinn, Thomas P; Cabral, Pablo

    2012-10-01

    In this work Nimotuzumab (monoclonal antibody, recognizes the EGF-R) was radiolabeled with (177)Lu as a potential cancer therapy radiopharmaceutical. In-vitro cell binding studies and in-vivo biodistribution and imaging studies were performed to determine the radiochemical stability, targeting specificity and pharmacokinetics of the (177)Lu-labeled antibody. Nimotuzumab was derivatized with DOTA-NHS at room temperature for 2 hours. DOTA-Nimotuzumab was radiolabeled with (177)LuCl3 (15 MBq/mg) at 37°C for 1 h. The radiochemical purity was assessed by ITLC, silica gel and by RP-HPLC. Binding specificity studies were performed with EGF-R positive A431 human epithelial carcinoma and EGF-R negative MDA-MB-435 breast carcinoma cells. Biodistribution studies were performed in healthy female CD-1 mice at 1 h, 4 h, 24 h, and A431 xenografted nude mice at 10 min, 1 h, 4 h, 24 h, 48 h, and 96 h. SPECT-CT imaging studies were performed in A431 xenografted mice at 24 h post injection. DOTA-Nimotuzumab was efficiently labeled with (177) LuCl(3) at 37°C. The in vitro stability of labeled product was optimal over 24 h in buffered saline and mouse serum. Specific recognition of EGF-R by (177)Lu-DOTA-Nimotuzumab was observed in A431 cell binding studies. Biodistribution studies demonstrated increasing tumor uptake of (177)Lu-DOTA-Nimotuzumab over time, with tumor to muscle ratios of 6.26, 10.68, and 18.82 at 4 h, 24 h, and 96 h post injection. Imaging of A431 xenografted mice showed high uptake in the tumor. (177)Lu-DOTA-Nimotuzumab has the potential to be a promising therapy agent, which may be useful in the treatment of patients with EGF-R positive cancer.

  5. Phase 3 Trial of (177)Lu-Dotatate for Midgut Neuroendocrine Tumors.

    PubMed

    Strosberg, Jonathan; El-Haddad, Ghassan; Wolin, Edward; Hendifar, Andrew; Yao, James; Chasen, Beth; Mittra, Erik; Kunz, Pamela L; Kulke, Matthew H; Jacene, Heather; Bushnell, David; O'Dorisio, Thomas M; Baum, Richard P; Kulkarni, Harshad R; Caplin, Martyn; Lebtahi, Rachida; Hobday, Timothy; Delpassand, Ebrahim; Van Cutsem, Eric; Benson, Al; Srirajaskanthan, Rajaventhan; Pavel, Marianne; Mora, Jaime; Berlin, Jordan; Grande, Enrique; Reed, Nicholas; Seregni, Ettore; Öberg, Kjell; Lopera Sierra, Maribel; Santoro, Paola; Thevenet, Thomas; Erion, Jack L; Ruszniewski, Philippe; Kwekkeboom, Dik; Krenning, Eric

    2017-01-12

    Background Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ((177)Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. Methods We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either (177)Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) ((177)Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. Results At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the (177)Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the (177)Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the (177)Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the (177)Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame

  6. Evidence for inelastic neutron acceleration by the {sup 177}Lu isomer

    SciTech Connect

    Roig, O.; Belier, G.; Meot, V.; Daugas, J.-M.

    2006-11-15

    The neutron burnup cross section {sigma}{sub burnup}{sup m} on the long-lived metastable state of {sup 177}Lu has been measured from a specially designed isomeric target. The Maxwellian averaged cross section obtained for this reaction on {sup 177}Lu{sup m}(J{sup {pi}}=23/2{sup -}) is {sigma}{sub burnup}{sup 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 {sigma}{sub n,{gamma}} clearly shows a possible existence of {sup 177}Lu{sup m} deexcitation via (n,n{sup '}) inelastic neutron acceleration channels. The results are interpreted in terms of a statistical approach using parameters from a deformed optical potential calculation.

  7. Theranostic Radiopharmaceuticals Based on Gold Nanoparticles Labeled with (177)Lu and Conjugated to Peptides.

    PubMed

    Ferro-Flores, Guillermina; Ocampo-García, Blanca E; Santos-Cuevas, Clara L; de María Ramírez, Flor; Azorín-Vega, Erika P; Meléndez-Alafort, Laura

    2015-01-01

    Gold nanoparticles (AuNPs) have been proposed for a variety of medical applications such as localized heat sources for cancer treatment and drug delivery systems. The conjugation of peptides to AuNPs produces stable multimeric systems with target-specific molecular recognition. Lutetium- 177 ((177)Lu) has been successfully used in peptide radionuclide therapy. Recently, (177)Lu-AuNPs conjugated to different peptides have been proposed as a new class of theranostic radiopharmaceuticals. These radioconjugates may function simultaneously as molecular imaging agents, radiotherapy systems and thermal-ablation systems. This article covers advancements in the design, synthesis, physicochemical characterization, molecular recognition assessment and preclinical therapeutic efficacy of gold nanoparticles radiolabeled with (177)Lu and conjugated to RGD (-Arg-Gly-Asp-), Lys(3)-Bombesin and Tat(49-57) peptides.

  8. Evaluation of two intraoperative gamma detectors for assessment of (177)Lu activity concentration in vivo.

    PubMed

    Sandblom, Viktor; Ståhl, Ingun; Olofsson Bagge, Roger; Forssell-Aronsson, Eva

    2017-12-01

    Patients with somatostatin receptor-expressing neuroendocrine tumours can be treated with intravenously administered (177)Lu-octreotate. Few patients are cured with the present protocol due to the current dose limitation of normal organs at risk, such as the kidneys. By locally administering (177)Lu-octreotate to the liver for the purpose of treating liver metastases, a substantially reduced absorbed dose to organs at risk could be achieved. The development of such a technique requires the capability of measuring the (177)Lu activity concentration in tissues in vivo. The aim of this study was to evaluate different performance parameters of two commercially available intraoperative gamma detectors in order to investigate whether intraoperative gamma detector measurements could be used to determine (177)Lu activity concentration in vivo. Measurements were made using different sources containing (177)Lu. Response linearity, sensitivity, spatial resolution and its depth dependence, organ thickness dependence of the measured count rate and tumour detectability were assessed for two intraoperative gamma detectors. The two detectors (a scintillation and a semiconductor detector) showed differences in technical performance. For example, the sensitivity was higher for the scintillation detector, while the spatial resolution was better for the semiconductor detector. Regarding organ thickness dependence and tumour detectability, similar results were obtained for both detectors, and even relatively small simulated tumours of low tumour-to-background activity concentration ratios could be detected. Acceptable results were obtained for both detectors, although the semiconductor detector proved more advantageous for our purpose. The measurements demonstrated factors that must be corrected for, such as organ thickness or dead-time effects. Altogether, intraoperative gamma detector measurements could be used to determine (177)Lu activity concentration in vivo.

  9. [177Lu]Bz-DTPA-EGF: Preclinical characterization of a potential radionuclide targeting agent against glioma.

    PubMed

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

    2004-04-01

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

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

    PubMed

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

    2015-04-01

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

  11. 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.

    PubMed

    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.

  12. Camptothecin Enhances Cell Death Induced by (177)Lu-EDTMP in Osteosarcoma Cells.

    PubMed

    Kumar, Chandan; Vats, Kusum; Lohar, Sharad P; Korde, Aruna; Samuel, Grace

    2014-10-01

    Lutetium-177 is an assured therapeutic radionuclide with favorable half-life and suitable β(-) energy. Radiolabeled (177)Lu-EDTMP (Ethylenediamine tetramethylene phosphonic acid) is by and large used for bone pain palliation in cancer patients. In vitro cell studies are carried out in osteosarcoma cells MG-63 to evaluate the combined effect of anticancer drug camptothecin (CPT) and (177)Lu-EDTMP. Two concentrations of (177)Lu-EDTMP (3.7 and 37 MBq) were incubated with MG63 cell line for 48 hours with and without pretreatment of CPT (10 nM) for 1 hour. After completion of incubation, the cells were harvested and cellular toxicity was estimated by LDH, MTT, and trypan blue dye. Apoptotic DNA fragmentation was estimated by ELISA kit. The expression of proteins such as bcl2, PARP, and MAPK (mitogen-activated protein kinase) that were related to apoptotic signaling pathways was assessed by western blotting. The results indicated that cellular toxicity and apoptosis were relatively higher in MG63 cells that were treated with CPT prior to treating with (177)Lu-EDTMP in comparison with the corresponding individual controls.

  13. Dose response of pancreatic neuroendocrine tumors treated with peptide receptor radionuclide therapy using 177Lu-DOTATATE.

    PubMed

    Ilan, Ezgi; Sandström, Mattias; Wassberg, Cecilia; Sundin, Anders; Garske-Román, Ulrike; Eriksson, Barbro; Granberg, Dan; Lubberink, Mark

    2015-02-01

    Peptide receptor radionuclide therapy (PRRT) is a promising treatment for patients with neuroendocrine tumors, giving rise to improved survival. Dosimetric calculations in relation to PRRT have been concentrated to normal organ dosimetry in order to limit side effects. However, the relation between the absorbed dose to the tumor and treatment response has so far not been established. Better knowledge in this respect may improve the understanding of treatment effects, allow for improved selection of those patients who are expected to benefit from PRRT, and avoid unnecessary treatments. The aim of the present work was to evaluate the dose-response relationship for pancreatic neuroendocrine tumors treated with PRRT using (177)Lu-DOTATATE. Tumor-absorbed dose calculations were performed for 24 lesions in 24 patients with metastasized pancreatic neuroendocrine tumors treated with repeated cycles of (177)Lu-DOTATATE at 8-wk intervals. The absorbed dose calculations relied on sequential SPECT/CT imaging at 24, 96, and 168 h after infusion of (177)Lu-DOTATATE. The unit density sphere model from OLINDA was used for absorbed dose calculations. The absorbed doses were corrected for partial-volume effect based on phantom measurements. On the basis of these results, only tumors larger than 2.2 cm in diameter at any time during the treatment were included for analysis. To further decrease the effect of partial-volume effect, a subgroup of tumors (>4.0 cm) was analyzed separately. Tumor response was evaluated by CT using Response Evaluation Criteria In Solid Tumors. Tumor-absorbed doses until best response ranged approximately from 10 to 340 Gy. A 2-parameter sigmoid fit was fitted to the data, and a significant correlation between the absorbed dose and tumor reduction was found, with a Pearson correlation coefficient (R(2)) of 0.64 for tumors larger than 2.2 cm and 0.91 for the subgroup of tumors larger than 4.0 cm. The largest tumor reduction was 57% after a total absorbed dose

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

    DTIC Science & Technology

    2010-09-01

    hypothesis is that the addition of 177Lu- J591 to ketoconazole will improve time to radiographically apparent metastases in men with biochemically...endpoint will be to compare the percentage of men with metastases at 18 months receiving ketoconazole plus 177Lu-J591 vs ketoconazole plus trace...phase II trial of 177lu radiolabeled monoclonal antibody J591 (177Lu-J591) and ketoconazole in patients (pts) with high-risk castrate biochemically

  15. Reducing renal uptake of 90Y- and 177Lu-labeled alpha-melanocyte stimulating hormone peptide analogues

    SciTech Connect

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

    2006-06-15

    The purpose of this study was to improve the tumor-to-kidney uptake ratios of 90Y- and 177Lu-[1,2,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid-Re-Cys,D-Phe,Arg]alpha-melanocyte stimulating hormone (DOTA-RE(Arg)CCMSH), through coupling a negatively charged glutamic acid (Glu) to the peptide sequence. A new peptide of DOTA-Re(Glu,Arg)CCMSH was designed, synthesized and labeled with 90Y and 177Lu. Pharmacokinetics of 90Y- and 177Lu-DOTA-RE(Glu,Arg)CCNSH were determined in B16/F1 murine melanoma-bearing C57 mice. Both exhibited significantly less renal uptake than 90Y- and 177Lu-DOTA-Re(Arg)CCMSH at 30 min and at 2, 3, and 24 h after dose administration. The renal uptake values of 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH were 28.16% and 28.81% of those of 90Y- and 177Lu-DOTA-RE(Arg)CCMSH, respectively, at 4 hr post-injection. We also showed higher tumor-to-kidney uptake ratios 2.28 and 1.69 times that of 90Y- and 177Lu-DOTA-Re(Arg)CCMSH, respectively, at 4 h post-injection. The90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH activity accumulation was low in normal organs except for kidneys. 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 90Y- and 177Lu-DOTA-Re(Glu,Arg)CCMSH, facilitating their potential applications as radiopharmaceuticals for targeted radionuclide therapy of melanoma.

  16. Direct evidence for inelastic neutron 'acceleration' by {sup 177}Lu{sup m}

    SciTech Connect

    Roig, O.; Meot, V.; Rosse, B.; Belier, G.; Daugas, J.-M.; Morel, P.; Letourneau, A.; Menelle, A.

    2011-06-15

    The inelastic neutron acceleration cross section on the long-lived metastable state of {sup 177}Lu has been measured using a direct method. High-energy neutrons have been detected using a specially designed setup placed on a cold neutron beam extracted from the ORPHEE reactor in Saclay. The 146{+-}19 b inelastic neutron acceleration cross section in the ORPHEE cold neutron flux confirms the high cross section for this process on the {sup 177}Lu{sup m} isomer. The deviation from the 258{+-}58 b previously published obtained for a Maxwellian neutron flux at a 323 K temperature could be explained by the presence of a low energy resonance. Resonance parameters are deduced and discussed.

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

    PubMed

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

    2016-12-01

    Peptide receptor therapy with (177)Lu-labelled somatostatin analogues is a promising tool in the management of patients with inoperable or metastasized neuroendocrine tumours. The aim of this work was to perform accurate activity quantification of (177)Lu in complex anthropomorphic geometry using advanced correction algorithms. Acquisitions were performed on the higher (177)Lu photopeak (208keV) using a Philips IRIX gamma camera provided with medium-energy collimators. System calibration was performed using a 16mL Jaszczak sphere surrounded by non-radioactive water. Attenuation correction was performed using μ-maps derived from CT data, while scatter and septal penetration corrections were performed using the transmission-dependent convolution-subtraction method. SPECT acquisitions were finally corrected for dead time and partial volume effects. Image analysis was performed using the commercial QSPECT software. The quantitative SPECT approach was validated on an anthropomorphic phantom provided with a home-made insert simulating a hepatic lesion. Quantitative accuracy was studied using three tumour-to-background activity concentration ratios (6:1, 9:1, 14:1). For all acquisitions, the recovered total activity was within 12% of the calibrated activity both in the background region and in the tumour. Using a 6:1 tumour-to-background ratio the recovered total activity was within 2% in the tumour and within 5% in the background. Partial volume effects, if not properly accounted for, can lead to significant activity underestimations in clinical conditions. In conclusion, accurate activity quantification of (177)Lu can be obtained if activity measurements are performed with equipment traceable to primary standards, advanced correction algorithms are used and acquisitions are performed at the 208keV photopeak using medium-energy collimators. Copyright © 2016 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

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

    PubMed Central

    Bailey, Dale L; Hennessy, Thomas M; Willowson, Kathy P; Henry, E Courtney; Chan, David LH; Aslani, Alireza; Roach, Paul J

    2016-01-01

    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. PMID:27904871

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

    PubMed

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

    2010-01-01

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

  20. (177)Lu-DOTATATE treatment in neuroendocrine tumours. A preliminary study.

    PubMed

    Hervás, I; Bello, P; Falgas, M; Del Olmo, M I; Torres, I; Olivas, C; Vera, V; Oliván, P; Yepes, A M

    Therapy with radiolabelled somatostatin analogue peptides is a promising new therapy to treat neuroendocrine tumours. The aim of this preliminary study is to present our experience with (177)Lu-DOTATATE therapy, and evaluate tolerability and short-term efficacy in patients with tumours expressing somatostatin receptors. A total of 7 patients with metastatic neuroendocrine tumours were treated, each with 4 doses of (177)Lu-DOTATATE. The treatment response was evaluated in the form of biochemical response (tumour markers), imaging methods (somatostatin receptor scintigraphy, computed tomography, and magnetic resonance), and functional and quality of life responses using the Karnofsky performance status scale. Treatment toxicity was also evaluated. The results obtained were as follows: Biochemical response: 60% of patients showed tumour marker levels returning to normal, while they decreased significantly in the remaining 40%. Imaging response: 85.7% had a partial response, while 14.3% showed stable disease. All (100%) patients showed a significant improvement in quality of life, with increased Karnofsky scale scores. No patient had acute or chronic toxicity, and subacute transient haematological toxicity was observed in 42.8% of patients. Despite being a preliminary study, it was found that treatment with (177)Lu-DOTATATE is a safe treatment with few side effects, and an objective response was achieved in most patients. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  1. Radiolabeling of monoclonal anti-CD105 with (177)Lu for potential use in radioimmunotherapy.

    PubMed

    Lee, So-Young; Hong, Young-Don; Felipe, Penelope M; Pyun, Mi-Sun; Choi, Sun-Ju

    2009-01-01

    In this study, we carried out a radioimmunoconjugation using (177)Lu with anti-CD105 (endoglin) monoclonal antibody for an angiogenesis targeting. CD105 has been shown to be a more useful marker to identify proliferating endothelium involved in tumor angiogenesis than panendothelial markers. We optimized the labeling of the anti-CD105 monoclonal antibody with (177)Lu by using cysteine derivative isothiocyanatobenzyl-DTPA (DTPA-NCS) as BFCA. Under the optimal conditions, labeling yield was greater than 99%. Immunoactivity of the radioimmunoconjugate was investigated using combinations of radioanalytical and bioanalytical techniques (ITLC-SG, Cyclone phosphorimager, SDS-PAGE and ELISA). For the biological evaluations we carried out a cell binding assay and a biodistribution study using mice bearing Calu6 lung cancer cell xenografts. The tumor-to-blood ratio was 11.16:1 24h post-injection. In conclusion, the anti-CD105 monoclonal antibody for an angiogenesis targeting was effectively radioconjugated with (177)Lu. And the biodistribution study showed a high specificity for accumulating in tumor tissues. This radioimmunoconjugate is applicable to detect angiogenesis sites in various diseases and to treat tumors.

  2. [177Lu-PSMA-617 therapy, dosimetry and follow-up in patients with metastatic castration-resistant prostate cancer].

    PubMed

    Fendler, Wolfgang P; Kratochwil, Clemens; Ahmadzadehfar, Hojjat; Rahbar, Kambiz; Baum, Richard P; Schmidt, Matthias; Pfestroff, Andreas; Lützen, Ulf; Prasad, Vikas; Heinzel, Alexander; Heuschkel, Martin; Ruf, Juri; Bartenstein, Peter; Krause, Bernd J

    2016-06-28

    Radioligand therapy (RLT) using 177Lu labelled inhibitors of the prostate-specific membrane antigen (177Lu-PSMA) is performed in patients with metastatic castration-resistant prostate cancer (mCRPC) after exhaustion of other options. German University Clinics offer RLT since 2013 on a compassionate use basis. The present consensus document includes recommendations for RLT with 177Lu-PSMA-617. These consensus statements were developed by an expert panel formed by the German Society of Nuclear Medicine (DGN) in December 2015. Statements include recommendations for indication, baseline tests, therapy protocol, concomitant therapy, dosimetry, and follow-up. Consensus recommendations aim to inform the attending medical staff, standardize 177Lu-PSMA-617 RLT, and improve quality of individual patient care.

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

    NASA Astrophysics Data System (ADS)

    Wang, Hsin-Ell; Yu, Hung-Man; Lu, Yi-Ching; Heish, Ning-Ning; Tseng, Yun-Long; Huang, Kuang-Liang; Chuang, Kuo-Tang; Chen, Chin-Hsiung; Hwang, Jeng-Jong; Lin, Wuu-Jyh; Wang, Shyh-Jen; Ting, Gann; Whang-Peng, Jacqueline; Deng, Win-Ping

    2006-12-01

    In vivo characterization and dosimetric analysis has been performed to evaluate the potential of pegylated liposomes as carriers of radionuclides in tumor internal radiotherapy. MethodsThe DTPA/PEG-liposomes were synthesized with a medium size of 110 nm, conjugated with 111In/ 177Lu-(oxine) 3 to afford 111In/ 177Lu-liposome. The stability of 111In/ 177Lu-liposome in serum was investigated. The biodistribution, scintigraphic imaging and pharmacokinetics of 111In/ 177Lu-liposomes after intravenous(i.v.) injection into C-26 tumor-bearing BALB/cByJ mice were studied. Radiation dose was estimated by MIRD-III program. ResultsThe incorporation efficiency of 111In/ 177Lu into liposomes was 95%. After incubation at 37 °C for 72 h in serum, more than 83% of radioactivity was still retained in the intact 111In/ 177Lu-liposomes. The biodistribution of 111In-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 177Lu-liposomes. Scintigraphic imaging with 111In-liposomes showed unambiguous tumor images at 48 h p.i. Dose estimation showed that the absorbed dose in tumor from 177Lu-liposomes was 5.74×10 -5 Gy/MBq. ConclusionsThis 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.

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

    PubMed

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

    PubMed

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

    2016-06-01

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

  6. Biodistribution, Pharmacokinetics, and Dosimetry of (177)Lu-, (90)Y-, and (111)In-Labeled Somatostatin Receptor Antagonist OPS201 in Comparison to the Agonist (177)Lu-DOTATATE: The Mass Effect.

    PubMed

    Nicolas, Guillaume P; Mansi, Rosalba; McDougall, Lisa; Kaufmann, Jens; Bouterfa, Hakim; Wild, Damian; Fani, Melpomeni

    2017-09-01

    Radiolabeled somatostatin receptor (SSTR) antagonists have shown in vivo higher uptake in SSTR-expressing tumors than agonists. In this preclinical study, the SSTR2 antagonist OPS201 (DOTA-JR11; DOTA-[Cpa-c(DCys-Aph(Hor)-DAph(Cbm)-Lys-Thr-Cys)-DTyr-NH2]) labeled with (177)Lu, (90)Y, and (111)In was compared with the SSTR2 agonist (177)Lu-DOTATATE. Methods: Biodistribution, pharmacokinetics, SPECT/CT, and dosimetry studies were performed to assess the bioequivalence of all radiotracers. Use of escalated peptide mass and nephroprotective agents were systematically investigated. Results: The tumor residence time was 15.6 h (13.4-17.7) for (177)Lu-OPS201 (10 pmol) and 6.4 h (5.4-7.3) for (177)Lu-DOTATATE, resulting in a 2.5-times-higher tumor dose for the antagonist than for the agonist (0.854 vs. 0.333 mGy/MBq for a 4-cm tumor). The overall tumor-to-kidney dose ratio was approximately 24% and 32% higher for (177)Lu-OPS201 than for (90)Y-OPS201 and (177)Lu-DOTATATE, respectively. (111)In-OPS201 had a biodistribution significantly different from (90)Y-OPS201 and is therefore not a surrogate for (90)Y-OPS201 dosimetry studies. Importantly, and in contrast to (177)Lu-DOTATATE, injection of 10, 200, and 2,000 pmol of (177)Lu-OPS201 did not cause any relevant tumor saturation, with tumor uptake 4 h after injection: 23.9, 24.9, and 18.8 percentage of injected activity per gram of tissue (%IA/g), respectively, for the antagonist (P > 0.05), as compared with 17.8, 12.0, and 9.9 %IA/g for the agonist (P < 0.05). Increasing the peptide mass of (177)Lu-OPS201 from 10 to 200 pmol drastically decreased the effective dose from 0.0908 to 0.0184 mSv/MBq and decreased the uptake in the liver, bone marrow, and all SSTR2-expressing organs; thus, the therapeutic index improved considerably. Lysine and succinylated gelatine, alone or in combination, significantly reduced the renal dose of (177)Lu-OPS201 compared with the control group, by 45%, 25%, and 40%, respectively (P < 0.05). The

  7. 177Lu-labeled HPMA Copolymers Utilizing Cathepsin B and S Cleavable Linkers: Synthesis, Characterization and Preliminary In Vivo Investigation in a Pancreatic Cancer Model

    PubMed Central

    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 177Lu, the peptide-polymer conjugates were renamed 177Lu- metabolically active copolymers (177Lu-MACs) with the corresponding designation 177Lu-MAC0, 177Lu-MAC1 and 177Lu-MAC2. Results In vivo evaluation of the 177Lu-MACs was performed in a HPAC human pancreatic cancer xenograft mouse model. 177Lu-MAC1 and 177Lu-MAC2 demonstrated 3.1 and 2.1 fold lower liver retention, respectively, compared to control (177Lu-MAC0) at 72 h post-injection. With regard to spleen retention, 177Lu-MAC1 and 177Lu-MAC2 each exhibited a nearly fourfold lower retention, relative to control, at the 72 h time point. However, the tumor accumulation of the 177Lu-MAC0 was two to three times greater than 177Lu-MAC1 and 177Lu-MAC2 at the same time point. The MAL approach demonstrated the capability of substantially reducing the non-target retention of the 177Lu-labeled HPMA copolymers. Conclusions While further studies are needed to optimize the pharmacokinetics of the 177Lu

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

    PubMed

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

    2014-05-01

    Patient-specific dosimetry of lutetium-177 ((177)Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts and the 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. (177)Lu SPECT images of a phantom with known activity concentration ratio between the uniform background and filled hollow spheres were acquired for three different collimators: low-energy high resolution (LEHR), low-energy general purpose (LEGP) and medium-energy general purpose (MEGP). Counts were collected in several energy windows, and scatter correction was performed by applying different methods such as effective scatter source estimation (ESSE), triple-energy and dual-energy window, double-photopeak window and downscatter correction. The intensity ratio between the spheres and the background was measured and corrected for the partial volume effect and used to compare the performance of the methods. Low-energy collimators combined with 208 keV energy windows give rise to artefacts. For the 113 keV energy window, large differences were observed in the ratios for the spheres. For MEGP collimators with the ESSE correction technique, the measured ratio was close to the real ratio, and the differences between spheres were small. For quantitative (177)Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated and the real ratio is less than 10% for both energy windows.

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

    PubMed Central

    Lagerburg, Vera; Klausen, Thomas L.; Holm, Søren

    2014-01-01

    Purpose Patient-specific dosimetry of lutetium-177 (177Lu)-DOTATATE treatment in neuroendocrine tumours is important, because uptake differs across patients. Single photon emission computer tomography (SPECT)-based dosimetry requires a conversion factor between the obtained counts and the 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 177Lu SPECT images of a phantom with known activity concentration ratio between the uniform background and filled hollow spheres were acquired for three different collimators: low-energy high resolution (LEHR), low-energy general purpose (LEGP) and medium-energy general purpose (MEGP). Counts were collected in several energy windows, and scatter correction was performed by applying different methods such as effective scatter source estimation (ESSE), triple-energy and dual-energy window, double-photopeak window and downscatter correction. The intensity ratio between the spheres and the background was measured and corrected for the partial volume effect and used to compare the performance of the methods. Results Low-energy collimators combined with 208 keV energy windows give rise to artefacts. For the 113 keV energy window, large differences were observed in the ratios for the spheres. For MEGP collimators with the ESSE correction technique, the measured ratio was close to the real ratio, and the differences between spheres were small. Conclusion For quantitative 177Lu imaging MEGP collimators are advised. Both energy peaks can be utilized when the ESSE correction technique is applied. The difference between the calculated and the real ratio is less than 10% for both energy windows. PMID:24525900

  10. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients.

    PubMed

    Rahbar, Kambiz; Ahmadzadehfar, Hojjat; Kratochwil, Clemens; Haberkorn, Uwe; Schäfers, Michael; Essler, Markus; Baum, Richard P; Kulkarni, Harshad R; Schmidt, Matthias; Drzezga, Alexander; Bartenstein, Peter; Pfestroff, Andreas; Luster, Markus; Lützen, Ulf; Marx, Marlies; Prasad, Vikas; Brenner, Winfried; Heinzel, Alexander; Mottaghy, Felix M; Ruf, Juri; Meyer, Philipp Tobias; Heuschkel, Martin; Eveslage, Maria; Bögemann, Martin; Fendler, Wolfgang Peter; Krause, Bernd Joachim

    2017-01-01

    (177)Lu-labeled PSMA-617 is a promising new therapeutic agent for radioligand therapy (RLT) of patients with metastatic castration-resistant prostate cancer (mCRPC). Initiated by the German Society of Nuclear Medicine, a retrospective multicenter data analysis was started in 2015 to evaluate efficacy and safety of (177)Lu-PSMA-617 in a large cohort of patients. One hundred forty-five patients (median age, 73 y; range, 43-88 y) with mCRPC were treated with (177)Lu-PSMA-617 in 12 therapy centers between February 2014 and July 2015 with 1-4 therapy cycles and an activity range of 2-8 GBq per cycle. Toxicity was categorized by the common toxicity criteria for adverse events (version 4.0) on the basis of serial blood tests and the attending physician's report. The primary endpoint for efficacy was biochemical response as defined by a prostate-specific antigen decline ≥ 50% from baseline to at least 2 wk after the start of RLT. A total of 248 therapy cycles were performed in 145 patients. Data for biochemical response in 99 patients as well as data for physician-reported and laboratory-based toxicity in 145 and 121 patients, respectively, were available. The median follow-up was 16 wk (range, 2-30 wk). Nineteen patients died during the observation period. Grade 3-4 hematotoxicity occurred in 18 patients: 10%, 4%, and 3% of the patients experienced anemia, thrombocytopenia, and leukopenia, respectively. Xerostomia occurred in 8%. The overall biochemical response rate was 45% after all therapy cycles, whereas 40% of patients already responded after a single cycle. Elevated alkaline phosphatase and the presence of visceral metastases were negative predictors and the total number of therapy cycles positive predictors of biochemical response. The present retrospective multicenter study of (177)Lu-PSMA-617 RLT demonstrates favorable safety and high efficacy exceeding those of other third-line systemic therapies in mCRPC patients. Future phase II/III studies are warranted to

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

    PubMed Central

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

    2015-01-01

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in

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

    DOE PAGES

    Frost, Sofia H. L.; Frayo, Shani L.; Miller, Brian W.; ...

    2015-03-18

    Purpose Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targetingmore » either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Methods Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibodystreptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. Results The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTAbiotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. Conclusion 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT

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

    PubMed

    Frost, Sofia H L; Frayo, Shani L; Miller, Brian W; Orozco, Johnnie J; Booth, Garrett C; Hylarides, Mark D; Lin, Yukang; Green, Damian J; Gopal, Ajay K; Pagel, John M; Bäck, Tom A; Fisher, Darrell R; Press, Oliver W

    2015-01-01

    Pretargeted radioimmunotherapy (PRIT) is a multi-step method of selectively delivering high doses of radiotherapy to tumor cells while minimizing exposure to surrounding tissues. Yttrium-90 (90Y) and lutetium-177 (177Lu) are two of the most promising beta-particle emitting radionuclides used for radioimmunotherapy, which despite having similar chemistries differ distinctly in terms of radiophysical features. These differences may have important consequences for the absorbed dose to tumors and normal organs. Whereas 90Y has been successfully applied in a number of preclinical and clinical radioimmunotherapy settings, there have been few published pretargeting studies with 177Lu. We therefore compared the therapeutic potential of targeting either 90Y or 177Lu to human B-cell lymphoma xenografts in mice. Parallel experiments evaluating the biodistribution, imaging, dosimetry, therapeutic efficacy, and toxicity were performed in female athymic nude mice bearing either Ramos (Burkitt lymphoma) or Granta (mantle cell lymphoma) xenografts, utilizing an anti-CD20 antibody-streptavidin conjugate (1F5-SA) and an 90Y- or 177Lu-labeled 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA)-biotin second step reagent. The two radionuclides displayed comparable biodistributions in tumors and normal organs; however, the absorbed radiation dose delivered to tumor was more than twice as high for 90Y (1.3 Gy/MBq) as for 177Lu (0.6 Gy/MBq). More importantly, therapy with 90Y-DOTA-biotin was dramatically more effective than with 177Lu-DOTA-biotin, with 100% of Ramos xenograft-bearing mice cured with 37 MBq 90Y, whereas 0% were cured using identical amounts of 177Lu-DOTA-biotin. Similar results were observed in mice bearing Granta xenografts, with 80% of the mice cured with 90Y-PRIT and 0% cured with 177Lu-PRIT. Toxicities were comparable with both isotopes. 90Y was therapeutically superior to 177Lu for streptavidin-biotin PRIT approaches in these human lymphoma xenograft

  14. [(177)Lu-PSMA therapy : Current evidence for use in the treatment of patients with metastatic prostate cancer].

    PubMed

    Boegemann, M; Schrader, A J; Rahbar, K

    2017-10-06

    Despite significant progress in the treatment of metastatic castration-resistant prostate cancer (mCRPC) in recent years (including agents targeting androgen receptor signaling, chemotherapy, and (223)Ra), most of these patients still succumb to prostate cancer. Recently, (177)lutetium prostate-specific membrane antigen radioligand therapy ((177)Lu-PSMA-RLT) has been increasingly used within compassionate use provisions in these patients in Germany and showed promising efficacy. Establishment of the current position of (177)Lu-PSMA-RLT in mCRPC in 2017. Presentation of the therapy landscape in mCRPC and the current challenges within treatment and survey of the available data on (177)Lu-PSMA-RLT after PubMed-based research. In several larger retrospective studies, (177)Lu-PSMA-RLT seems to be an encouraging new option with the potential to extend overall survival while displaying a favorable toxicity profile. Prospective trials are urgently needed to confirm these encouraging results found in retrospective analyses with (177)Lu-PSMA-RLT in the treatment of mCRPC.

  15. (44)Sc-PSMA-617 for radiotheragnostics in tandem with (177)Lu-PSMA-617-preclinical investigations in comparison with (68)Ga-PSMA-11 and (68)Ga-PSMA-617.

    PubMed

    Umbricht, Christoph A; Benešová, Martina; Schmid, Raffaella M; Türler, Andreas; Schibli, Roger; van der Meulen, Nicholas P; Müller, Cristina

    2017-12-01

    The targeting of the prostate-specific membrane antigen (PSMA) is of particular interest for radiotheragnostic purposes of prostate cancer. Radiolabeled PSMA-617, a 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid (DOTA)-functionalized PSMA ligand, revealed favorable kinetics with high tumor uptake, enabling its successful application for PET imaging ((68)Ga) and radionuclide therapy ((177)Lu) in the clinics. In this study, PSMA-617 was labeled with cyclotron-produced (44)Sc (T 1/2 = 4.04 h) and investigated preclinically for its use as a diagnostic match to (177)Lu-PSMA-617. (44)Sc was produced at the research cyclotron at PSI by irradiation of enriched (44)Ca targets, followed by chromatographic separation. (44)Sc-PSMA-617 was prepared under standard labeling conditions at elevated temperature resulting in a radiochemical purity of >97% at a specific activity of up to 10 MBq/nmol. (44)Sc-PSMA-617 was evaluated in vitro and compared to the (177)Lu- and (68)Ga-labeled match, as well as (68)Ga-PSMA-11 using PSMA-positive PC-3 PIP and PSMA-negative PC-3 flu prostate cancer cells. In these experiments it revealed similar in vitro properties to that of (177)Lu- and (68)Ga-labeled PSMA-617. Moreover, (44)Sc-PSMA-617 bound specifically to PSMA-expressing PC-3 PIP tumor cells, while unspecific binding to PC-3 flu cells was not observed. The radioligands were investigated with regard to their in vivo properties in PC-3 PIP/flu tumor-bearing mice. (44)Sc-PSMA-617 showed high tumor uptake and a fast renal excretion. The overall tissue distribution of (44)Sc-PSMA-617 resembled that of (177)Lu-PSMA-617 most closely, while the (68)Ga-labeled ligands, in particular (68)Ga-PSMA-11, showed different distribution kinetics. (44)Sc-PSMA-617 enabled distinct visualization of PC-3 PIP tumor xenografts shortly after injection, with increasing tumor-to-background contrast over time while unspecific uptake in the PC-3 flu tumors was not observed. The in vitro

  16. 177Lu-DOTA-HH1, a Novel Anti-CD37 Radio-Immunoconjugate: A Study of Toxicity in Nude Mice

    PubMed Central

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

    2014-01-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-11-01

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

  19. Realistic multi-cellular dosimetry for (177)Lu-labelled antibodies: model and application.

    PubMed

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

    2016-10-07

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

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

    SciTech Connect

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

    2015-03-01

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

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

    PubMed

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

    2016-08-01

    This study aimed at the preparation and evaluation of (177)Lu-CHX-A''-DTPA-Bevacizumab for targeting VEGF over-expressing cancers. Bevacizumab conjugated to p-NCS-Bn-CHX-A''-DTPA was radiolabeled with (177)Lu. The radioimmunoconjugate characterized by SE-HPLC exhibited radiochemical purity of 98.0±0.6%. In vitro stability was retained upto 4 days at 37°C. In vitro cell binding studies showed good uptake by VEGF expressing U937 tumor cells. Biodistribution studies in melanoma model showed significant uptake and retention of (177)Lu-CHX-A''-DTPA-Bevacizumab in tumor with reduction in uptake in presence of cold Bevacizumab confirming its specificity to VEGF. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Preparation and Evaluation of (177)Lu-Labeled Gemcitabine: An Effort Toward Developing Radiolabeled Chemotherapeutics for Targeted Therapy Applications.

    PubMed

    Ghosh, Subhajit; Das, Tapas; Sarma, Haladhar D; Dash, Ashutosh

    2017-09-06

    Gemcitabine, a nucleoside analogue, is used as a chemotherapeutic drug for the treatment of a wide variety of cancers. Therefore, radiolabeled gemcitabine may have potential as a radiotherapeutic agent for the treatment of various types of cancers. In the present work, an attempt has been made to radiolabel gemcitabine with (177)Lu and study the preliminary biological behavior of (177)Lu-labeled gemcitabine in tumor-bearing animal model. Gemcitabine was coupled with p-NCS-benzyl-DOTA, a bifunctional chelating agent, to facilitate radiolabeling with (177)Lu. The p-NCS-benzyl-DOTA-gemcitabine conjugate was radiolabeled with (177)Lu, produced in-house and characterized by high-performance liquid chromatography. Tumor targeting potential of the radiolabeled agent was determined by biodistribution studies in Swiss mice bearing fibrosarcoma tumors. (177)Lu-gemcitabine was prepared with a radiochemical purity of 95.7% ± 0.3% under the optimized reaction conditions. The radiolabeled agent showed adequate in vitro stability in normal saline as well as in human blood serum. Preliminary biological studies revealed rapid and significant accumulation of the radiotracer in the tumorous lesions along with fast clearance of activity from blood and other vital organs/tissue. Although tumor uptake gradually reduced with time, tumor to blood and tumor to muscle ratios were improved due to the comparatively faster clearance of activity from the nontarget organs/tissue. The present study demonstrates the preliminary potential of (177)Lu-gemcitabine for targeted radiotherapy. However, further studies are warranted to assess its potential for radiotherapeutic applications.

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

    PubMed Central

    Schüler, Emil; Larsson, Maria; Parris, Toshima Z.; Johansson, Martin E.; Helou, Khalil; Forssell-Aronsson, Eva

    2015-01-01

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

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

    DTIC Science & Technology

    2014-09-01

    hypothesis is that the addition of 177Lu-J591 to ketoconazole will improve time to radiographically apparent metastases in men with biochemically...primary endpoint will be to compare the percentage of men with metastases at 18 months receiving ketoconazole plus 177Lu-J591 vs ketoconazole plus trace

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

    DTIC Science & Technology

    2015-09-01

    modalities). The hypothesis is that the addition of 177Lu-J591 to ketoconazole will improve time to radiographically apparent metastases in men with...The primary endpoint will be to compare the percentage of men with metastases at 18 months receiving ketoconazole plus 177Lu-J591 vs ketoconazole plus

  6. A systematic study on the utility of CHX-A''-DTPA-NCS and NOTA-NCS as bifunctional chelators for (177)Lu radiopharmaceuticals.

    PubMed

    Pandey, Usha; Gamre, Naresh; Lohar, Sharad Pandurang; Dash, Ashutosh

    2017-09-01

    This paper describes the evaluation of [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine-pentaacetic acid (CHX-A''-DTPA-NCS) and 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (NOTA-NCS) as bifunctional chelators for (177)Lu. While (177)Lu-CHX-A''-DTPA-NCS could be obtained in high yields at equimolar ratios of lutetium to CHX-A''-DTPA-NCS, >95% yield of (177)Lu-NOTA-NCS could be achieved at 1:2M ratio of lutetium to NOTA-NCS. Trace metals reduced the yields of (177)Lu-NOTA-NCS significantly as compared to (177)Lu-CHX-A''-DTPA-NCS. In vitro stability of (177)Lu-CHX-A''-DTPA-NCS was also superior to (177)Lu-NOTA-NCS. It could be concluded from this study that among the two chelators evaluated, CHX-A''-DTPA-NCS is more appropriate for preparation of (177)Lu radiopharmaceuticals. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Use of (177)Lu-dotatate in the treatment of iodine refractory thyroid carcinomas.

    PubMed

    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.

  8. Targeted Radionuclide Therapy with A 177Lu-labeled Anti-HER2 Nanobody

    PubMed Central

    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 (MW < 15 kDa) functional antigen-binding fragments that are derived from heavy chain-only camelid antibodies. Here, we show that the extend of kidney retention of nanobodies 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

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

    PubMed

    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 (MW<15 kDa) functional antigen-binding fragments that are derived from heavy chain-only camelid antibodies. Here, we show that the extend of kidney retention of nanobodies 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

  10. Aminocarboxylate complexes and octreotide complexes with no carrier added 177Lu, 166Ho and 149Pm.

    PubMed

    Li, Wen Ping; Smith, C Jeff; Cutler, Cathy S; Hoffman, Timothy J; Ketring, Alan R; Jurisson, Silvia S

    2003-04-01

    Several aminocarboxylate complexes of the "no carrier added" (NCA) radiolanthanides (149)Pm, (166)Ho and (177)Lu were evaluated using our in vitro hydroxyapatite and serum stability model and in vivo in normal CF-1 mice [10]. The aminocarboxylate chelates evaluated with the NCA radiolanthanides for in vitro stability were EDTA, CDTA, DTPA, MA-DTPA and DOTA. In addition, the NCA radiolanthanide complexes with DTPA-octreotide (DTPA-OCT) were synthesized and evaluated, as a model for a peptide conjugated aminocarboxylate complex. The biodistribution studies of the NCA complexes with DTPA, DOTA and DTPA-OCT showed that the in vitro model correctly predicted the in vivo stability of the radiolanthanide complexes, with Ln-DOTA > Ln-DTPA > Ln-DTPA-OCT.

  11. Assessment of cell death mechanisms triggered by (177)Lu-anti-CD20 in lymphoma cells.

    PubMed

    Azorín-Vega, E; Rojas-Calderón, E; Martínez-Ventura, B; Ramos-Bernal, J; Serrano-Espinoza, L; Jiménez-Mancilla, N; Ordaz-Rosado, D; Ferro-Flores, G

    2017-04-12

    The aim of this research was to evaluate the cell cycle redistribution and activation of early and late apoptotic pathways in lymphoma cells after treatment with (177)Lu-anti-CD20. Experimental and computer models were used to calculate the radiation absorbed dose to cancer cell nuclei. The computer model (Monte Carlo, PENELOPE) consisted of twenty spheres representing cells with an inner sphere (cell nucleus) embedded in culture media. Radiation emissions of the radiopharmaceutical located in cell membranes and in culture media were considered for nuclei dose calculations. Flow cytometric analyses demonstrated that doses as low as 4.8Gy are enough to induce cell cycle arrest and activate late apoptotic pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Measurement of reaction kinetics of [(177)Lu]Lu-DOTA-TATE using a microfluidic system.

    PubMed

    Liu, Z; Schaap, K S; Ballemans, L; de Zanger, R; de Blois, E; Rohde, M; Oehlke, E

    2017-09-12

    Microfluidic synthesis techniques can offer improvement over batch syntheses which are currently used for radiopharmaceutical production. These improvements are, for example, better mixing of reactants, more efficient energy transfer, less radiolysis, faster reaction optimization, and overall improved reaction control. However, scale-up challenges hinder the routine clinical use, so the main advantage is currently the ability to optimize reactions rapidly and with low reactant consumption. Translating those results to clinical systems could be done based on calculations, if kinetic constants and diffusion coefficients were known. This study describes a microfluidic system with which it was possible to determine the kinetic association rate constants for the formation of [(177)Lu]Lu-DOTA-TATE under conditions currently used for clinical production. The kinetic rate constants showed a temperature dependence that followed the Arrhenius equation, allowing the determination of Arrhenius parameters for a Lu-DOTA conjugate (A = 1.24 ± 0.05 × 10(19) M(-1) s(-1), EA = 109.5 ± 0.1 × 10(3) J mol(-1)) for the first time. The required reaction time for the formation of [(177)Lu]Lu-DOTA-TATE (99% yield) at 80 °C was 44 s in a microfluidic channel (100 μm). Simulations done with COMSOL Multiphysics® indicated that processing clinical amounts (3 mL reaction solution) in less than 12 min is possible in a micro- or milli-fluidic system, if the diameter of the reaction channel is increased to over 500 μm. These results show that a continuous, microfluidic system can become a viable alternative to the conventional, batch-wise radiolabelling technique.

  13. Predictors of Response to Radioligand Therapy of Metastatic Castrate-Resistant Prostate Cancer with 177Lu-PSMA-617.

    PubMed

    Ferdinandus, Justin; Eppard, Elisabeth; Gaertner, Florian C; Kürpig, Stefan; Fimmers, Rolf; Yordanova, Anna; Hauser, Stefan; Feldmann, Georg; Essler, Markus; Ahmadzadehfar, Hojjat

    2017-02-01

    Radioligand therapy (RLT) with (177)Lu-PSMA-617 (PSMA is prostate-specific membrane antigen) is a novel targeted therapy for metastatic prostate cancer. In this study, we evaluated the effect of different pretherapeutic parameters on the therapeutic response measured by prostate-specific antigen (PSA) 2 mo after RLT.

  14. Anti-EGFRvIII monoclonal antibody armed with 177Lu: in vivo comparison of macrocyclic and acyclic ligands

    PubMed Central

    Hens, Marc; Vaidyanathan, Ganesan; Zhao, Xiao-Guang; Bigner, Darell D.; Zalutsky, Michael R.

    2010-01-01

    Introduction Monoclonal antibody (mAb) L8A4 binds specifically to the epidermal growth factor receptor variant III (EGFRvIII) that is present on gliomas but not normal tissues, and is internalized rapidly after receptor binding. Because of the short range of its β-emissions, labeling this mAb with177Lu would be an attractive approach for the treatment of residual tumor margins remaining after surgical debulking of brain tumors. Materials and Methods L8A4 mAb was labeled with 177Lu using the acyclic ligands [(R)-2-Amino-3-(4-isothiocyanatophenyl)propyl]-trans-(S,S)-cyclohexane-1,2-diamine- pentaacetic acid (CHX-A″-DTPA) and 2-(4-Isothiocyanatobenzyl)-6-methyldiethylene- triaminepentaacetic acid (1B4M-DTPA), and the macrocyclic ligands S-2-(4- Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane-tetraacetic acid (C-DOTA) and α-(5-isothiocyanato-2-methoxyphenyl)-1,4,7,10-tetraazacyclododecane-1,4,7,10- tetraacetic acid (MeO-DOTA). Paired-label tissue distribution experiments were performed in athymic mice bearing subcutaneous EGFRvIII-expressing U87.)EGFR glioma xenografts over a period of 1 to 8 days to directly compare 177Lu-labeled L8A4 to L8A4 labeled with 125I using N-succinimidyl 4-guanidinomethyl-3-[125I]iodobenzoate ([125I]SGMIB). Results Except with C-DOTA, tumor uptake for the 177Lu-labeled mAb was significantly higher than the co-administered radioiodinated preparation; however, this was also the case for spleen, liver, bone and kidneys. Tumor:normal tissue ratios for 177Lu-1B4M-DTPA-L8A4 and to an even greater extent, 177Lu-MeO-DOTA-L8A4, were higher than those for [125I]SGMIB-L8A4 in most other tissues. Conclusions Tumor and normal tissue distribution patterns for this anti-EGFRvIII mAb were dependent on the nature of the bifunctional chelate used for 177Lu labeling. Optimal results were obtained with 1B4M-DTPA and MeO-DOTA, suggesting no clear advantage for acyclic vs. macrocyclic ligands for this application. PMID:20870149

  15. Therapeutic efficacy of 177Lu-CHX-A″-DTPA-hu3S193 radioimmunotherapy in prostate cancer is enhanced by EGFR inhibition or docetaxel chemotherapy

    PubMed Central

    Kelly, Marcus P; Lee, Sze Ting; Lee, F-T; Smyth, Fiona E; Davis, Ian D.; Brechbiel, Martin W; Scott, Andrew M

    2008-01-01

    Background This study investigated the biodistribution and therapeutic efficacy of Lutetium-177 (177Lu) radiolabeled anti-Lewis Y monoclonal antibody hu3S193 radioimmunotherapy (RIT) in mice bearing prostate cancer xenografts. The ability of Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor AG1478 and docetaxel chemotherapy to enhance the efficacy of RIT was also assessed in vivo. Methods The in vitro cytotoxicity of 177Lu labeled hu3S193 on Ley positive DU145 prostate cancer cells was assessed using proliferation assays, with induction of apoptosis measured by ELISA. The in vivo biodistribution and tumor localization of 177Lu-hu3S193 was assessed in mice bearing established DU145 tumor xenografts. The efficacy and maximum tolerated dose of 177Lu-hu3S193 RIT in vivo was determined by a dose escalation study. EGFR inhibitor AG1478 or docetaxel chemotherapy was administered at sub-therapeutic doses in conjunction with RIT in vivo. Results 177Lu-hu3S193 mediated significant induction of cytotoxicity and apoptosis in vitro. In vivo analysis of 177Lu-hu3S193 biodistribution demonstrated specific targeting of DU145 prostate cancer xenografts, with maximal tumor uptake of 33.2 ± 3.9 %ID/g observed at 120 hr post injection. In RIT studies, 177Lu-hu3S193 caused specific and dose-dependent inhibition of prostate cancer tumor growth. A maximum tolerated dose of 350μCi was determined for 177Lu-hu3S193. Combination of 177Lu-hu3S193 RIT with EGFR inhibitor AG1478 or docetaxel chemotherapy both significantly improved efficacy. Conclusions 177Lu-hu3S193 RIT is effective as a single agent in the treatment of Ley positive prostate cancer models. The enhancement of RIT by AG1478 or docetaxel indicates the promise of combined modality strategies. PMID:18942092

  16. Preclinical evaluation of (177)lu-nimotuzumab: a potential tool for radioimmunotherapy of epidermal growth factor receptor-overexpressing tumors.

    PubMed

    Vera, Denis Rolando Beckford; Eigner, Sebastian; Beran, Milos; Henke, Katerina Eigner; Laznickova, Alice; Laznicek, Milan; Melichar, Frantisek; Chinol, Marco

    2011-06-01

    The humanized monoclonal antibody Nimotuzumab (h-R3) has demonstrated an exceptional and better clinical profile than other monoclonal antibodies for immunotherapy of epidermal growth factor receptor-overexpressing tumors. This work deals with the preparation and radiolabeling optimization of (177)Lu-Nimotuzumab and their preclinical evaluation. Nimotuzumab was conjugated with S-2-(4-isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid (p-SCN-Bn-DOTA), testing different molar ratios. The immunoconjugates were characterized. The radiolabeling with (177)Lu was optimized. Radioimmunoconjugates stability was tested in 2-[bis[2-[bis(carboxymethyl)amino]ethyl]amino]acetic acid (DTPA) excess and human serum. In vitro studies were performed in tumor model cell lines. Receptor-specific binding was tested by competitive inhibition. (177)Lu-Nimotuzumab in vivo studies were conducted in healthy and xenograft animals. Nimotuzumab conjugates were obtained with high purity. Radiolabeling yield and specific activities ranged from 63.6% to 94.5% and from 748 to 1142 MBq/mg, respectively. The stability in DTPA excess and human serum was 95.9% and 93.2% after 10 days, respectively. The radioimmunoconjugate showed specific receptor binding in tumor cell lines. Biodistribution in healthy animals showed the typical behavior of the immunoconjugates based on monoclonal antibodies. The study in xenografts mice demonstrated uptake of (177)Lu-Nimotuzumab in the tumor and reticuloendothelial organs. (177)Lu-Nimotuzumab was obtained with high purity and specific activities under optimal conditions without significant loss in immunoreactivity and might be a potential radioimmunoconjugate for radioimmunotherapy of tumors with epidermal growth factor receptor overexpression.

  17. Biodistribution and dosimetry results from a phase 1 trial of (177)Lu-lilotomab satetraxetan antibody-radionuclide conjugate therapy.

    PubMed

    Blakkisrud, Johan; Holtedahl, Jon Erik; Løndalen, Ayca; Dahle, Jostein; Bach-Gansmo, Tore; Holte, Harald; Nygaard, Stine; Kolstad, Arne; Stokke, Caroline

    2017-08-28

    (177)Lu-lilotomab satetraxetan is a novel antibody radionuclide conjugate (ARC) currently in a phase 1/2a first-in-human dosage escalation trial for patients with relapsed CD37+ indolent non-Hodgkin lymphoma. The aim of this study was to investigate biodistribution and absorbed doses to organs at risk. Methods: A total of seven patients treated with (177)Lu-lilotomab satetraxetan were included for dosimetry. Patients were grouped based on two different pre-dosing regimens (with and without pre-dosing with 40 mg lilotomab) and were treated with different levels of activity per body weight (10, 15 and 20 MBq/kg). All patients were pre-treated with rituximab. Serial planar and SPECT/CT-images were used to determine time activity curves and patient specific masses for organs with (177)Lu-lilotomab satetraxetan uptake. Doses were calculated with OLINDA/EXM. Results: Organs with distinct uptake of (177)Lu-lilotomab satetraxetan, in addition to red bone marrow and tumors, were liver, spleen and kidneys. Largest uptake was found in the spleen, where doses ranged from 1.54 to 3.60 mGy/MBq. The liver received 0.70 to 1.15 mGy/MBq. The kidneys received the lowest dose of the source organs investigated; 0.16 to 0.79 mGy/MBq. No statistical significant differences in soft tissue absorbed doses for the two pre-dosing regimens were found. Whole body dose ranged from 0.08 to 0.17 mGy/MBq. Conclusion: The biodistribution study for patients treated with (177)Lu-lilotomab satetraxetan revealed highest physiological uptake in liver and spleen, besides red marrow. For all dosage levels investigated, doses were found modest when compared to commonly assumed tolerance limits. Copyright © 2017 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

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

    PubMed

    Cho, Eun-Ha; Lim, Jae Cheong; Lee, So-Young; Jung, Sung-Hee

    2016-07-01

    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 (177)Lu, 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 (177)Lu-labeling, in which the peptides were radiolabeled with (177)Lu by a high radiolabeling yield. A competitive displacement of (125)I-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 (177)Lu-DOTA-[Nle]-cCCK has higher binding affinity than (177)Lu-DOTA-glucose-CCK and can be a potential candidate as a targeting modality for a CCK receptor over-expressing tumors. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  19. Radiation Nanomedicine for EGFR-Positive Breast Cancer: Panitumumab-Modified Gold Nanoparticles Complexed to the β-Particle-Emitter, (177)Lu.

    PubMed

    Yook, Simmyung; Cai, Zhongli; Lu, Yijie; Winnik, Mitchell A; Pignol, Jean-Philippe; Reilly, Raymond M

    2015-11-02

    Our objective was to construct a novel radiation nanomedicine for treatment of breast cancer (BC) expressing epidermal growth factor receptors (EGFR), particularly triple-negative tumors (TNBC). Gold nanoparticles (AuNP; 30 nm) were modified with polyethylene glycol (PEG) chains (4 kDa) derivatized with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) chelators for complexing the β-emitter, (177)Lu and with PEG chains (5 kDa) linked to panitumumab for targeting BC cells expressing EGFR. The AuNP were further coated with PEG chains (2 kDa) to stabilize the particles to aggregation. The binding and internalization of EGFR-targeted AuNP ((177)Lu-T-AuNP) into BC cells was studied and compared to nontargeted (177)Lu-NT-AuNP. The cytotoxicity of (177)Lu-T-AuNP and (177)Lu-NT-AuNP was measured in clonogenic assays using BC cells with widely different EGFR densities: MDA-MB-468 (10(6) receptors/cell), MDA-MB-231 (10(5) receptors/cell), and MCF-7 cells (10(4) receptors/cell). Radiation absorbed doses to the cell nucleus of MDA-MB-468 cells were estimated based on subcellular distribution. Darkfield and fluorescence microscopy as well as radioligand binding assays revealed that (177)Lu-T-AuNP were specifically bound by BC cells dependent on their EGFR density whereas the binding and internalization of (177)Lu-NT-AuNP was significantly lower. The affinity of binding of (177)Lu-T-AuNP to MDA-MB-468 cells was reduced by 2-fold compared to (123)I-labeled panitumumab (KD = 1.3 ± 0.2 nM vs 0.7 ± 0.4 nM, respectively). The cytotoxicity of (177)Lu-T-AuNP was dependent on the amount of radioactivity incubated with BC cells, their EGFR density and the radiosensitivity of the cells. The clonogenic survival (CS) of MDA-MB-468 cells overexpressing EGFR was reduced to <0.001% at the highest amount of (177)Lu-T-AuNP tested (4.5 MBq; 6 × 10(11) AuNP per 2.5 × 10(4)-1.2 × 10(5) cells). (177)Lu-T-AuNP were less effective for killing MDA-MB-231 cells or MCF-7 cells with

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  1. Fast voxel-level dosimetry for (177)Lu labelled peptide treatments.

    PubMed

    Hippeläinen, E; Tenhunen, M; Sohlberg, A

    2015-09-07

    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

  2. Comparison of the Therapeutic Response to Treatment with a 177Lu-Labeled Somatostatin Receptor Agonist and Antagonist in Preclinical Models.

    PubMed

    Dalm, Simone U; Nonnekens, Julie; Doeswijk, Gabriela N; de Blois, Erik; van Gent, Dik C; Konijnenberg, Mark W; de Jong, Marion

    2016-02-01

    Peptide receptor scintigraphy and peptide receptor radionuclide therapy using radiolabeled somatostatin receptor (SSTR) agonists are successfully used in the clinic for imaging and treatment of neuroendocrine tumors. Contrary to the paradigm that internalization and the resulting accumulation of radiotracers in cells is necessary for efficient tumor targeting, recent studies have demonstrated the superiority of radiolabeled SSTR antagonists for imaging purposes, despite little to no internalization in cells. However, studies comparing the therapeutic antitumor effects of radiolabeled SSTR agonists versus antagonists are lacking. The aim of this study was to directly compare the therapeutic effect of (177)Lu-DOTA-octreotate, an SSTR agonist, and (177)Lu-DOTA-JR11, an SSTR antagonist. We analyzed radiotracer uptake (both membrane-bound and internalized fractions) and the produced DNA double-strand breaks, by determining the number of p53 binding protein 1 foci, after incubating SSTR2-positive cells with (177)Lu-diethylene triamine pentaacetic acid, (177)Lu-DOTA-octreotate, or (177)Lu-DOTA-JR11. Also, biodistribution studies were performed in tumor-xenografted mice to determine the optimal dose for therapy experiments. Afterward, in vivo therapy experiments comparing the effect of (177)Lu-DOTA-octreotate and (177)Lu-DOTA-JR11 were performed in this same animal model. We found a 5-times-higher uptake of (177)Lu-DOTA-JR11 than of (177)Lu-DOTA-octreotate. The major part (88% ± 1%) of the antagonist uptake was membrane-bound, whereas 74% ± 3% of the total receptor agonist uptake was internalized. Cells treated with (177)Lu-DOTA-JR11 showed 2 times more p53-binding protein 1 foci than cells treated with (177)Lu-DOTA-octreotate. Biodistribution studies with (177)Lu-DOTA-JR11 (0.5 μg/30 MBq) resulted in the highest tumor radiation dose of 1.8 ± 0.7 Gy/MBq, 4.4 times higher than the highest tumor radiation dose found for (177)Lu-DOTA-octreotate. In vivo therapy studies

  3. Distinct microRNA Expression Profiles in Mouse Renal Cortical Tissue after 177Lu-octreotate Administration

    PubMed Central

    Schüler, Emil; Parris, Toshima Z.; Helou, Khalil; Forssell-Aronsson, Eva

    2014-01-01

    Aim The aim of this study was to investigate the variation of the miRNA expression levels in normal renal cortical tissue after 177Lu-octreotate administration, a radiopharmaceutical used for treatment of neuroendocrine cancers. Methods Female BALB/c nude mice were i.v. injected with 1.3, 3.6, 14, 45, or 140 MBq 177Lu-octreotate, while control animals received saline. The animals were killed at 24 h after injection and total RNA, including miRNA, was extracted from the renal cortical tissue and hybridized to the Mouse miRNA Oligo chip 4plex to identify differentially regulated miRNAs between exposed and control samples. Results In total, 57 specific miRNAs were differentially regulated in the exposed renal cortical tissues with 1, 29, 21, 27, and 31 miRNAs identified per dose-level (0.13, 0.34, 1.3, 4.3, and 13 Gy, respectively). No miRNAs were commonly regulated at all dose levels. miR-194, miR-107, miR-3090, and miR-3077 were commonly regulated at 0.34, 1.3, 4.3, and 13 Gy. Strong effects on cellular mechanisms ranging from immune response to p53 signaling and cancer-related pathways were observed at the highest absorbed dose. Thirty-nine of the 57 differentially regulated miRNAs identified in the present study have previously been associated with response to ionizing radiation, indicating common radiation responsive pathways. Conclusion In conclusion, the 177Lu-octreotate associated miRNA signatures were generally dose-specific, thereby illustrating transcriptional regulation of radiation responsive miRNAs. Taken together, these results imply the importance of miRNAs in early immunological responses in the kidneys following 177Lu-octreotate administration. PMID:25386939

  4. [177Lu-DOTA]0-D-Phe1-Tyr3-Octreotide (177Lu-DOTATOC) For Peptide Receptor Radiotherapy in Patients with Advanced Neuroendocrine Tumours: A Phase-II Study

    PubMed Central

    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

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed

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

    2015-08-07

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

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

    NASA Astrophysics Data System (ADS)

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

    2015-08-01

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

  8. 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.

    PubMed

    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.

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

    DTIC Science & Technology

    2012-09-01

    The hypothesis is that the addition of 177Lu-J591 to ketoconazole will improve time to radiographically apparent metastases in men with...primary endpoint will be to compare the percentage of men with metastases at 18 months receiving ketoconazole plus 177Lu-J591 vs ketoconazole plus...J951 vs 111In-J591 (control) and undergo planar gamma camera imaging with SPECT following infusion. All pts receive ketoconazole plus hydrocortisone

  10. Therapeutic efficacy of a 177Lu-labeled DOTA conjugated alpha-melanocyte-stimulating hormone peptide in a murine melanoma-bearing mouse model.

    PubMed

    Miao, Yubin; Shelton, Tiffani; Quinn, Thomas P

    2007-06-01

    The aim of this study was to examine the therapeutic efficacy of (177)Lu-DOTA-Re(Arg(11))CCMSH in the B16/F1 murine melanoma-bearing mouse model. (177)Lu-DOTA-Re(Arg(11))CCMSH was prepared in 0.5 M NH(4)OAc at a pH of 5.4. Two (2) treatment groups of 10 melanoma-bearing C57 mice were administrated with 2 x 18.5 MBq and 1 x 37.0 MBq of (177)Lu-DOTA-Re(Arg(11))CCMSH through the tail vein, respectively. One (1) group of 10 melanoma-bearing C57 mice was injected with saline placebos as untreated melanoma-bearing controls. In contrast to the untreated melanoma-bearing control group, (177)Lu-DOTA-Re(Arg(11))CCMSH administration yielded rapid and lasting therapeutic effects in the treatment groups. (177)Lu-DOTA-Re(Arg(11))CCMSH treatment decreased the tumor growth rate and significantly (p > 0.05) prolonged the survival time of melanoma-bearing C57 mice. Treatment with 2 x 18.5 MBq or 1 x 37.0 MBq of (177)Lu-DOTA-Re(Arg(11))CCMSH significantly extended the mean survival of tumor-bearing mice from 13.3 to 15.1 and 16.2 days, respectively. (177)Lu-DOTA-Re(Arg(11))CCMSH treatment produced no observed acute renal toxicity. The therapy study results revealed that (177)Lu-DOTA-Re(Arg(11))CCMSH yielded quantitative therapeutic effects in B16/F1 melanoma-bearing mice and appeared to be a promising radiolabeled peptide for the targeted radionuclide therapy of melanoma.

  11. H6phospa-Trastuzumab: Bifunctional Methylenephosphonate-based Chelator with 89Zr, 111In and 177Lu

    PubMed Central

    Price, Eric W.; Zeglis, Brian M.

    2013-01-01

    The acyclic chelator H6phospa and the bifunctional derivative p-SCN-Bn-H6phospa have been synthesized using nosyl protection chemistry and evaluated with 89Zr, 111In, and 177Lu. The p-SCN-Bn-H6phospa derivative was successfully conjugated to trastuzumab with isotopic dilution assays indicating 3.3 ± 0.1 chelates per antibody and in vitro cellular binding assays indicating an immunoreactivity value of 97.9 ± 2.6%. Radiolabeling of the H6phospa-trastuzumab immunoconjugate was achieved with 111In in 70–90% yields at room temperature in 30 minutes, while 177Lu under the same conditions produced more inconsistent yields of 40–80%. Stability experiments in human serum revealed the 111In-phospa-trastuzumab complex to be 52.0 ± 5.3% intact after 5 days at 37 °C, while the 177Lu-phospa-trastuzumab to be only 2.0 ± 0.3% intact. Small animal SPECT/CT imaging using mice bearing subcutaneous SKOV-3 ovarian cancer xenografts was performed, and it was found that 111In-phospa-trastuzumab successfully identified and delineated small (~2 mm in diameter) tumors from surrounding tissues, despite visible uptake in the kidneys and bone due to moderate chelate instability. As predicted from stability assays in serum, the 177Lu-phospa-trastuzumab conjugate served as a negative control and displayed no tumor uptake, with high uptake in bones indicating rapid and complete radiometal dissociation and suggesting a potential application of H6phospa in transient lanthanide chelation for bone-delivery. Radiolabeling with 89Zr was attempted, but even with elevated temperatures of 37 °C, the maximum observed radiometal incorporation over 18 hours was 12%. It can be concluded from this work that H6phospa is not superior to the previously studied H4octapa for use with 111In and 177Lu, but improvements in 89Zr radiolabeling were observed over H4octapa, suggesting H6phospa to be an excellent starting point for elaboration of 89Zr-based radiopharmaceutical development. To our knowledge, H6

  12. Intratumorally Injected 177Lu-Labeled Gold Nanoparticles: Gold Nanoseed Brachytherapy with Application for Neoadjuvant Treatment of Locally Advanced Breast Cancer.

    PubMed

    Yook, Simmyung; Cai, Zhongli; Lu, Yijie; Winnik, Mitchell A; Pignol, Jean-Philippe; Reilly, Raymond M

    2016-06-01

    Improvements in the treatment of locally advanced breast cancer (LABC) are needed. Our objective was to study a radiation nanomedicine (gold nanoseeds) composed of 30-nm gold nanoparticles (AuNP) modified with polyethyleneglycol (PEG) chains linked to DOTA for complexing the β-particle emitter (177)Lu and to panitumumab for targeting epidermal growth factor receptors (EGFR) ((177)Lu-T-AuNP) as a novel neoadjuvant brachytherapy for LABC. Nontargeted gold nanoseeds ((177)Lu-NT-AuNP) were constructed without panitumumab for comparison. (177)Lu-T-AuNP or (177)Lu-NT-AuNP was injected intratumorally in CD-1 athymic mice bearing subcutaneous EGFR-positive MDA-MB-468 human breast cancer tumors. Biodistribution and small-animal SPECT/CT imaging studies were performed to evaluate tumor and normal organ localization. A short-term (15 d) study was conducted to select the most effective amount of (177)Lu-T-AuNP or (177)Lu-NT-AuNP for treatment with long-term observation (90-120 d). Normal organ toxicities were assessed by monitoring body weight, blood cell counts, and serum alanine aminotransferase and creatinine. Radiation-absorbed doses in the tumor and normal organs were estimated by Monte Carlo N-Particle version 5.0 modeling. Tumor radioactivity concentrations were high at 1 h after injection (>300-400 percentage injected dose per gram [%ID/g]) but decreased by 2-3-fold at 48 h after injection. Normal organ uptake was low (<0.5 %ID/g) except for the liver and spleen (<3 %ID/g), increasing by 2-5-fold at 48 h after injection. Treatment with 4.5 MBq (6 × 10(11) AuNP) of (177)Lu-T-AuNP or (177)Lu-NT-AuNP arrested tumor growth over 90 d without normal organ toxicity, whereas tumors continued to grow in mice treated with unlabeled T-AuNP or (177)Lu-labeled PEG polymer not linked to AuNP. Survival was prolonged up to 120 d in mice treated with (177)Lu-T-AuNP or (177)Lu-NT-AuNP. Radiation-absorbed doses to the tumor were 30 and 22 Gy for (177)Lu-T-AuNP and (177)Lu

  13. 177Lu-antibody conjugates for single-cell kill of B-lymphoma cells in vitro and for therapy of micrometastases in vivo.

    PubMed

    Michel, Rosana B; Andrews, Philip M; Rosario, Adriane V; Goldenberg, David M; Mattes, M Jules

    2005-04-01

    Antibodies (Abs) conjugated to 177Lu, a relatively low-energy beta-particle emitter, were evaluated in vitro for their cytotoxic activity and in vivo for their therapeutic activity against disseminated B-cell lymphoma xenografts in SCID mice. 177Lu was compared with other beta-particle emitters ((131)I and 90Y), and also with emitters of low-energy electrons (LEEs, meaning Auger and conversion electrons of < 50 keV). The Abs used reacted with CD20, CD74 or HLA-DR, and the target cell was the Raji B lymphoma. Like the other beta-particle emitters, 177Lu was a potent and specific toxic agent in vitro, when conjugated to Abs recognizing high-density antigens. It appeared to be slightly less potent than (131)I per decay, but this difference was relatively small, and would not be a major factor in the selection of the optimal radionuclide for clinical use. The nonspecific toxicity from 177Lu was less than from 90Y, but 177Lu still produced greater nonspecific toxicity in vitro than LEE emitters. The maximum tolerated dose (MTD) of 177Lu-anti-CD74 in SCID mice was 1.81 MBq (49 microCi)/mouse. When this dose was administered on day 5 after tumor inoculation, significant protection was obtained, but considerably less than the protection obtained in previous experiments with LEE emitters (111)In and 67Ga. In conclusion, 177Lu has advantages over other available beta-particle emitters as a therapeutic agent, but its efficacy in the treatment of micrometastases seems to be less than that of LEE emitters, due to greater nonspecific toxicity. This conclusion, however, may not apply to therapy of macroscopic tumors.

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

    PubMed

    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.

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

    PubMed

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

    2016-01-01

    The accuracy of absorbed dose calculations in personalized internal radionuclide therapy is directly related to the accuracy of the activity (or activity concentration) estimates obtained at each of the imaging time points. MIRD Pamphlet no. 23 presented a general overview of methods that are required for quantitative SPECT imaging. The present document is next in a series of isotope-specific guidelines and recommendations that follow the general information that was provided in MIRD 23. This paper focuses on (177)Lu (lutetium) and its application in radiopharmaceutical therapy. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  16. Dose Mapping after Endoradiotherapy with (177)Lu-DOTATATE/-TOC by One Single Measurement after Four Days.

    PubMed

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

    2017-06-06

    Dosimetry of organs and tumors helps to assess risks and benefit of treatment with (177)Lu-DOTATATE/ TOC. However, it is often not performed in clinical routine because of additional efforts, the complexity of data collection and analysis, and the additional burden for the patients. Aiming at a simplification of dosimetry, we analyzed the accuracy of a theoretically substantiated approximation, which allows to calculate absorbed doses from a single measurement of the abdominal activity distribution. Methods: Activity kinetics were retrospectively assessed from planar images in 29 patients with neuroendocrine tumors (NET, n = 21) or meningioma (n = 8) after the administration of (177)Lu-DOTATATE (n = 22) or (177)Lu-DOTATOC (n = 7). Mono- or bi-exponential functions were fitted to measured data in 54 kidneys, 25 livers, 27 spleens, and 30 NET lesions. It was evaluated for each fit function how well the integral over time was represented by an approximation calculated as the product of the time tl of a single measurement, the expected reading at time tl, and the factor 2/ln(2). Tissue specific deviations of the approximation from the time integral were calculated for time points tl = 24, 48, 72, 96, 120, and 144 hours. Results: Correlation between time integral and approximation improved with increasing time tl. Pearson's r exceeded 0.95 for tl ≥ 96 hours in all tissues. Lowest maximum errors were observed at tl = 96 hours with deviations of the approximation from the time integral of median +5% (range, -9% to +17%) for kidneys, +6% (range, -7% to +12%) for livers, +8% (range, +2% to +20%) for spleens, and +6% (range, -11% to +16%) for NET lesions. Accuracy is reduced for measurements after 72 or 120 hours. For measurements after 24, 48, and 144 hours, the approximation leads to large deviations for some of the patients, in particular unacceptable underestimates of the absorbed dose to the kidneys. Conclusion: A single quantitative measurement of the abdominal

  17. Evaluation of affibody molecule-based PNA-mediated radionuclide pretargeting: Development of an optimized conjugation protocol and (177)Lu labeling.

    PubMed

    Altai, Mohamed; Westerlund, Kristina; Velletta, Justin; Mitran, Bogdan; Honarvar, Hadis; Karlström, Amelie Eriksson

    2017-07-12

    We have previously developed a pretargeting approach for affibody-mediated cancer therapy based on PNA-PNA hybridization. In this article we have further developed this approach by optimizing the production of the primary agent, ZHER2:342-SR-HP1, and labeling the secondary agent, HP2, with the therapeutic radionuclide (177)Lu. We also studied the biodistribution profile of (177)Lu-HP2 in mice, and evaluated pretargeting with (177)Lu-HP2 in vitro and in vivo. The biodistribution profile of (177)Lu-HP2 was evaluated in NMRI mice and compared to the previously studied (111)In-HP2. Pretargeting using (177)Lu-HP2 was studied in vitro using the HER2-expressing cell lines BT-474 and SKOV-3, and in vivo in mice bearing SKOV-3 xenografts. Using an optimized production protocol for ZHER2:342-SR-HP1 the ligation time was reduced from 15h to 30min, and the yield increased from 45% to 70%. (177)Lu-labeled HP2 binds specifically in vitro to BT474 and SKOV-3 cells pre-treated with ZHER2:342-SR-HP1. (177)Lu-HP2 was shown to have a more rapid blood clearance compared to (111)In-HP2 in NMRI mice, and the measured radioactivity in blood was 0.22±0.1 and 0.68±0.07%ID/g for (177)Lu- and (111)In-HP2, respectively, at 1h p.i. In contrast, no significant difference in kidney uptake was observed (4.47±1.17 and 3.94±0.58%ID/g for (177)Lu- and (111)In-HP2, respectively, at 1h p.i.). Co-injection with either Gelofusine or lysine significantly reduced the kidney uptake for (177)Lu-HP2 (1.0±0.1 and 1.6±0.2, respectively, vs. 2.97±0.87%ID/g in controls at 4h p.i.). (177)Lu-HP2 accumulated in SKOV-3 xenografts in BALB/C nu/nu mice when administered after injection of ZHER2:342-SR-HP1. Without pre-injection of ZHER2:342-SR-HP1, the uptake of (177)Lu-HP2 was about 90-fold lower in tumor (0.23±0.08 vs. 20.7±3.5%ID/g). The tumor-to-kidney radioactivity accumulation ratio was almost 5-fold higher in the group of mice pre-injected with ZHER2:342-SR-HP1. In conclusion, (177)Lu-HP2 was shown to

  18. Radiolanthanide-labeled monoclonal antibody CC49 for radioimmunotherapy of cancer: biological comparison of DOTA conjugates and 149Pm, 166Ho, and 177Lu.

    PubMed

    Mohsin, Huma; Jia, Fang; Sivaguru, Geethapriya; Hudson, Michael J; Shelton, Tiffani D; Hoffman, Timothy J; Cutler, Cathy S; Ketring, Alan R; Athey, Phillip S; Simón, Jaime; Frank, R Keith; Jurisson, Silvia S; Lewis, Michael R

    2006-01-01

    The radiolanthanides 149Pm, 166Ho, and 177Lu have decay characteristics suitable for radioimmunotherapy (RIT) of cancer. N-Hydroxysulfosuccinimidyl DOTA (DOTA-OSSu) and methoxy-DOTA (MeO-DOTA) were conjugated to the anti-TAG-72 monoclonal antibody CC49 for radiolabeling with 149Pm, 166Ho, and 177Lu. While both DOTA conjugates could be labeled to high specific activity with 177Lu, MeO-DOTA afforded superior conjugate stability, radiolabeling, and radiochemical purity. Pilot biodistributions in nude mice bearing LS174T human colon carcinoma xenografts demonstrated that MeO-DOTA afforded higher tumor uptake and lower kidney retention of 177Lu than DOTA-OSSu. The in vitro stability of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 was evaluated using serum and hydroxyapatite assays. Serum stability of radiolanthanide-labeled MeO-DOTA-CC49 followed a trend based on the coordination energies of the radiometals, with 177Lu showing the highest stability after 96 to 168 h at 37 C. In contrast, MeO-DOTA-CC49 labeled with all three radiolanthanides was >92% stable to hydroxyapatite challenge for 168 h at 37 C. Comprehensive biodistributions of 149Pm-, 166Ho-, and 177Lu-MeO-DOTA-CC49 were obtained in LS174T-bearing nude mice. Maximum tumor uptakes were 100.0% ID/g for 149Pm at 96 h, 69.5% ID/g for 166Ho at 96 h, and 132.4% ID/g for 177Lu at 168 h. Normal organ uptakes were generally low, except in the liver, spleen, and kidney at early time points. By 96 to 168 h postinjection, nontarget organ uptake decreased to approximately 7% ID/g (kidney), 12% ID/g (spleen), and 20% ID/g (liver) for each radiolanthanide. When labeled with 149Pm, 166Ho, and 177Lu, MeO-DOTA-CC49 has potential for RIT of colorectal cancer and other carcinomas.

  19. Dosimetry for (177)Lu-DKFZ-PSMA-617: a new radiopharmaceutical for the treatment of metastatic prostate cancer.

    PubMed

    Delker, Andreas; Fendler, Wolfgang Peter; Kratochwil, Clemens; Brunegraf, Anika; Gosewisch, Astrid; Gildehaus, Franz Josef; Tritschler, Stefan; Stief, Christian Georg; Kopka, Klaus; Haberkorn, Uwe; Bartenstein, Peter; Böning, Guido

    2016-01-01

    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 (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) (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 (177)Lu-DKFZ-PSMA-617. We suggest that (177)Lu-DKFZ-PSMA-617 is suitable for

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

    PubMed

    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

    Introdução: O objetivo deste artigo é rever a experiência do Instituto Português de Oncologia do Porto na terapêutica de tumores neuroendócrinos gastroenteropancreáticos com 177Lu-DOTA-TATE, tendo como principais pontos de análise a segurança e eficáciaterapêutica. Material e Métodos: Foi realizada uma análise retrospetiva dos processos clínicos de doentes com tumores neuroendócrinos gastroenteropancreáticos, submetidos a terapêutica com 177Lu-DOTA-TATE entre abril de 2011 e novembro de 2013. Resultados: Dos 36 casos revistos, 30 completaram os três ciclos de 177Lu-DOTA-TATE (83,3%). Nesses doentes foram registados: efeitos colaterais agudos em 8,9% dos ciclos; toxicidade hepática grau 3 CTCAE em 13,3% dos doentes (todos com alterações prévias da função hepática); ausência de toxicidade renal ou hematológica significativa; melhoria sintomática em 71,4% dos doentes; tempo mediano global desde o início da terapêutica até progressão de doença de 25,6 meses; tempo mediano global de sobrevivência desde o diagnóstico de 121,7 meses. Verificou-se um maior tempo livre de progressão de doença e de sobrevivência nos doentes com expressão elevada de recetores da somatostatina (p < 0,05). Discussão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE apresenta respostas clínicas favoráveis com segurança e boa tolerabilidade terapêutica, conforme evidenciado no nosso estudo pelos seguintes achados: melhoria dos sintomas na maioria dos doentes e aumento significativo do tempo livre de progressão de doença e da sobrevivência (sobretudo nos doentes com expressão elevada de sstr), com efeitos colaterais agudos e subagudos/crónicos significativos numa minoria de doentes. Conclusão: A peptide receptor radionuclide therapy com 177Lu-DOTA-TATE é uma terapêutica promissora, com benefícios reais em termos de eficácia e segurança nos doentes com tumores neuroendócrinos gastroenteropancreáticos.

  1. Optimization of GATE simulations for whole-body planar scintigraphic acquisitions using the XCAT male phantom with (177)Lu-DOTATATE biokinetics in a Siemens Symbia T2.

    PubMed

    Costa, G C A; Bonifácio, D A B; Sarrut, D; Cajgfinger, T; Bardiès, M

    2017-07-20

    Simulations of planar whole body acquisitions in therapeutic procedures are often extensively time-consuming and therefore rarely used. However, optimising tools and variance reduction techniques can be employed to overcome this problem. In this paper, a variety of features available in GATE are explored and their capabilities to reduce simulation time are evaluated. For this purpose, the male XCAT phantom was used as a virtual patient with (177)Lu-DOTATATE pharmacokinetic for whole body planar acquisition simulations in a Siemens Symbia T2 model. Activity distribution was divided into 8 compartments that were simulated separately. GATE optimization techniques included reducing the amount of time spent in both voxel and detector tracking. Some acceleration techniques led to a decrease of CPU-time by a factor of 167, while image statistics were kept constant. In that context, the simulation of therapeutic procedure imaging would still require 46days on a single CPU, but this could be reduced to hours on a dedicated cluster. Copyright © 2017. Published by Elsevier Ltd.

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

    PubMed Central

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

    2016-01-01

    Radiolabeled antibodies (mAbs) provide efficient tools for cancer therapy. The combination of low energy β−-emissions (500 keVmax; 130 keVave) along with a γ-emission for imaging makes 177Lu (T1/2 = 6.7 day) a suitable radionuclide for radioimmunotherapy (RIT) of tumor burdens possibly too large to treat with α-particle radiation. RIT with 177Lu-trastuzumab has proven to be effective for treatment of disseminated HER2 positive peritoneal disease in a pre-clinical model. To elucidate mechanisms originating from this RIT therapy at the molecular level, tumor bearing mice (LS-174T intraperitoneal xenografts) were treated with 177Lu-trastuzumab comparatively to animals treated with a non-specific control, 177Lu-HuIgG, and then to prior published results obtained using 212Pb-trastuzumab, an α-particle RIT agent. 177Lu-trastuzumab induced cell death via DNA double strand breaks (DSB), caspase-3 apoptosis, and interfered with DNA-PK expression, which is associated with the repair of DNA non-homologous end joining damage. This contrasts to prior results, wherein 212Pb-trastuzumab was found to down-regulate RAD51, which is involved with homologous recombination DNA damage repair. 177Lu-trastuzumab therapy was associated with significant chromosomal disruption and up-regulation of genes in the apoptotic process. These results suggest an inhibition of the repair mechanism specific to the type of radiation damage being inflicted by either high or low linear energy transfer radiation. Understanding the mechanisms of action of β−- and α-particle RIT comparatively through an in vivo tumor environment offers real information suitable to enhance combination therapy regimens involving α- and β−-particle RIT for the management of intraperitoneal disease. PMID:27196891

  3. Immuno-PET Imaging and Radioimmunotherapy of 64Cu-/177Lu-Labeled Anti-EGFR Antibody in Esophageal Squamous Cell Carcinoma Model.

    PubMed

    Song, In Ho; Lee, Tae Sup; Park, Yong Serk; Lee, Jin Sook; Lee, Byung Chul; Moon, Byung Seok; An, Gwang Il; Lee, Hae Won; Kim, Kwang Il; Lee, Yong Jin; Kang, Joo Hyun; Lim, Sang Moo

    2016-07-01

    Immuno-PET provides valuable information about tumor location, phenotype, susceptibility to therapy, and treatment response, especially to targeted radioimmunotherapy. In this study, we prepared antiepidermal growth factor receptor (EGFR) antibody via identical chelator, 3,6,9,15-tetraazabicyclo[9.3.1]-pentadeca-1(15),11,13-trience-3,6,9,-triacetic acid (PCTA), labeled with (64)Cu or (177)Lu to evaluate the EGFR expression levels using immuno-PET and the feasibility of radioimmunotherapy in an esophageal squamous cell carcinoma (ESCC) model. Cetuximab was conjugated with p-SCN-Bn-PCTA and radiolabeled with (64)Cu or (177)Lu. In vitro EGFR expression levels were determined and compared using flow cytometry and cell binding assay. In vivo EGFR expression levels were evaluated via immuno-PET imaging of (64)Cu-cetuximab and biodistribution analysis. Micro-SPECT/CT imaging, biodistribution, and radioimmunotherapy studies of (177)Lu-cetuximab were performed in the ESCC model. Therapeutic responses were monitored using (18)F-FDG PET and immunohistochemical staining. (64)Cu- or (177)Lu-labeled antibodies showed high radiolabeling yield (>98%), stability (>90%), and favorable immunoreactivity. In vitro EGFR status measured by cell binding assay was correlated with the flow cytometry data. Immuno-PET, micro-SPECT/CT, and biodistribution demonstrated specific uptake in ESCC tumors depending on the EGFR expression levels. Tumor accumulation of (64)Cu- and (177)Lu-cetuximab was peaked at 48 and 120 h, respectively. Radioimmunotherapy with (177)Lu-cetuximab showed significant inhibition of tumor growth (P < 0.01) and marked reduction of (18)F-FDG SUV compared with that of control (P < 0.05). Terminal deoxynucleotidyl transferase dUTP nick-end labeling positivity and Ki-67 staining indices increased and decreased, respectively, in the radioimmunotherapy group compared with other groups (P < 0.01). (64)Cu-cetuximab immuno-PET represented EGFR expression levels in ESCC tumors, and

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

    DTIC Science & Technology

    2011-09-01

    3 mm tumors (those not seen on standard imaging modalities). The hypothesis is that the addition of 177Lu-J591 to ketoconazole will improve time...receiving ketoconazole plus 177Lu-J591 vs ketoconazole plus trace-labeled 111In-J591 (i.e. placebo). Secondary endpoints include PSA response...receive ketoconazole plus hydrocortisone. The primary endpoint of the study is 18-month met-free survival. 140 pts will be treated to allow 80% power with

  5. Pretargeted Radioimmunotherapy of Prostate Cancer with an Anti-TROP-2×Anti-HSG Bispecific Antibody and a 177Lu-Labeled Peptide

    PubMed Central

    Frielink, Cathelijne; Goldenberg, David M.; Sharkey, Robert M.; Lütje, Susanne; McBride, William J.; Oyen, Wim J.G.; Boerman, Otto C.

    2014-01-01

    Abstract TROP-2 is a pancarcinoma marker that is expressed at high levels in many epithelial cancers, including prostate cancer (PC). The trivalent bispecific antibody TF12 (anti-TROP2×anti-HSG [histamine-succinyl-glycine]) has shown to effectively target PC. In this study, the efficacy of pretargeted radioimmunotherapy (PRIT) with multiple cycles of TF12 and 177Lu-labeled diHSG-peptide (IMP288) in mice with s.c. PC3 tumors was investigated and compared with that of conventional RIT with 177Lu-labeled anti-TROP-2 mAb hRS7. Methods: The potential of one, two, and three cycles of PRIT using the TF12 pretargeted 177Lu-IMP288 (41 MBq per cycle) was determined in mice with s.c. PC3 tumors, and compared with the efficacy and toxicity of RIT with 177Lu-hRS7 dosed at the maximum tolerated dose (11 MBq). Results: PRIT of two and three cycles showed significantly higher median survival (>150 days) compared with PRIT of one cycle of TF12 and 177Lu-IMP288 (111 days, p<0.001) or the controls (76 days, p<0.0001). All mice treated with the mAb 177Lu-hRS7 survived at the end of the experiment (150 days), compared with 80% in the mice that were treated with three cycles of PRIT and 70% in the group that received two cycles of PRIT. Clinically significant hematologic toxicity was found only in the groups that received either three cycles of PRIT (p<0.0009) or RIT (p<0.0001). Conclusions: TROP-2-expressing PC can be targeted efficiently with TF12 and radiolabeled IMP288. 177Lu-IMP288 accumulated rapidly in the tumors. PRIT of multiple cycles inhibited the growth of s.c. PC3 tumors. Clinically relevant hematological toxicity was observed in the group that received three cycles of PRIT; however, conventional RIT with the parent mAb 177Lu-hRS7 was at least as effective with similar toxicity. PMID:25226447

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

    PubMed

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

    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 ttoxicity 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

  7. PSMA-Targeted Radionuclide Therapy of Metastatic Castration-Resistant Prostate Cancer with 177Lu-Labeled PSMA-617.

    PubMed

    Kratochwil, Clemens; Giesel, Frederik L; Stefanova, Melsa; Benešová, Martina; Bronzel, Marcus; Afshar-Oromieh, Ali; Mier, Walter; Eder, Matthias; Kopka, Klaus; Haberkorn, Uwe

    2016-08-01

    Prostate-specific membrane antigen (PSMA) is an excellent target for radionuclide therapy of metastasized castration-resistant prostate cancer (mCRPC). Besides high affinity and long tumor retention, the DOTA-conjugated ligand PSMA-617 has low kidney uptake, making it an excellent choice for therapeutic application. We retrospectively report our experience with (177)Lu-PSMA-617-targeted radionuclide therapy in a case series of mCRPC patients resistant to other treatments. Patients with PSMA-positive tumor phenotypes were selected by molecular imaging. Thirty patients received 1-3 cycles of (177)Lu-PSMA-617. During therapy, pharmacokinetics and radiation dosimetry were evaluated. Blood cell count was checked every 2 wk after the first and every 4 wk after succeeding cycles. Prostate-specific antigen (PSA) was determined every 4 wk. Radiologic restaging was performed after 3 cycles. Twenty-one of 30 patients had a PSA response; in 13 of 30 the PSA decreased more than 50%. After 3 cycles, 8 of 11 patients achieved a sustained PSA response (>50%) for over 24 wk, which also correlated with radiologic response (decreased lesion number and size). Normally, acute hematotoxicity was mild. Diffuse bone marrow involvement was a risk factor for higher grade myelosuppression but could be identified by PSMA imaging in advance. Xerostomia, nausea, and fatigue occurred sporadically (<10%). Clearance of non-tumor-bound tracer was predominantly renal and widely completed by 48 h. Safety dosimetry revealed kidney doses of approximately 0.75 Gy/GBq, red marrow doses of 0.03 Gy/GBq, and salivary gland doses of 1.4 Gy/GBq, irrespective of tumor burden and consistent on subsequent cycles. Mean tumor-absorbed dose ranged from 6 to 22 Gy/GBq during cycle 1. (177)Lu-PSMA-617 is a promising new option for therapy of mCRPC and deserves more attention in larger prospective trials. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  8. (177)Lu-PSMA-617 radioligand therapy and outcome in patients with metastasized castration-resistant prostate cancer.

    PubMed

    Bräuer, Axel; Grubert, Lena Sophie; Roll, Wolfgang; Schrader, Andres Jan; Schäfers, Michael; Bögemann, Martin; Rahbar, Kambiz

    2017-09-01

    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 (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 (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 (177)Lu

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

    NASA Astrophysics Data System (ADS)

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

    2016-03-01

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

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

    PubMed

    Eriksson, Sophie E; Elgström, Erika; Bäck, Tom; Ohlsson, Tomas; Jensen, Holger; Nilsson, Rune; Lindegren, Sture; Tennvall, Jan

    2014-08-01

    Alpha-particle emitters, such as astatine-211 (211At), are generally considered suitable for the treatment of small cell clusters due to their short path length, while beta-particle emitters, for example, Lutetium-177 (177Lu), have a longer path length and are considered better 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. Rats bearing solid colon carcinoma tumors were treated with 400 MBq/kg body weight 177Lu-BR96. After 25 days, three groups of animals were given either 5 or 10 MBq/kg body weight of 211At-BR96 simultaneously with or without a blocking agent reducing halogen uptake in normal tissues. Control animals were not given any 211At-BR96. Myelotoxicity, body weight, tumor size, and development of metastases were monitored for 120 days. Tumors were undetectable in 90% of the animals on day 25, independent of treatment. Additional treatment with 211At-labeled antibodies did not reduce the proportion of animals developing metastases. The rats suffered from reversible myelotoxicity after treatment. Sequential administration of 177Lu-BR96 and 211At-BR96 resulted in tolerable toxicity providing halogen blocking but did not enhance the therapeutic effect.

  11. Biodistributions of 177Lu- and 111In- labeled 7E11 Antibodies to Prostate-Specific Membrane Antigen in Xenograft Model of Prostate Cancer and Potential Use of 111In-7E11 as a Pretherapeutic Agent for 177Lu-7E11 Radioimmunotherapy

    PubMed Central

    Pan, Mei-Hsiu; Gao, Dong-Wei; Feng, Jinjin; He, Jiang; Seo, Youngho; Tedesco, John; Wolodzko, John G.; Hasegawa, Bruce H.; Franc, Benjamin L.

    2010-01-01

    Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein highly expressed in many prostate cancers, and can be targeted with radiolabeled antibodies for diagnosis and treatment of this disease. To serve as a radioimmunotherapeutic agent, a kinetically inert conjugate is desired to maximize tumor uptake and tumor radiation dose with minimal nonspecific exposure to bone marrow and other major organs. In this study, we assessed the pharmacokinetics and biodistribution of the 7E11 monoclonal antibody (MAb) radiolabeled with the lutetium-177 (177Lu) - tetraazacyclododecanetetraacetic acid (DOTA) conjugate system (177Lu-7E11) versus those of the 7E11 MAb radiolabeled with the indium-111 (111In) – glycyl-tyrosyl-(N,-diethylenetriaminepentaacetic acid)-lysine hydrochloride (DTPA) conjugate system (111In-7E11, also known as ProstaScint®), to determine the feasibility of using 111In-7E11 as a pretherapeutic agent for 177Lu-7E11 radioimmunotherapy. Pharmacokinetic and biodistribution studies of 177Lu-7E11 in LNCaP xenograft mice were performed at 2, 8, 12, 24, 72, and 168 hours after radiopharmaceutical administration. For 111In-7E11, pharmacokinetic and biodistribution studies were performed at 8, 24, and 72 hours. Parallel studies of 177Lu-7E11 in nontumor bearing mice at 8, 24, and 72 hours postinjection served as controls. Gamma scintigraphy was performed, followed by autoradiography and tissue counting to demonstrate and quantify the distributions of radioconjugated MAb in the tumor and normal tissues. Both 177Lu- and 111In- 7E11 conjugates demonstrated an early blood pool phase in which uptake was dominated by the blood, lung, spleen and liver, followed by uptake and retention of the radiolabeled antibody in the tumor which was most prominent at 24 h. Total accumulation of radioconjugated MAb in tumor at 24 h was greater in the case of 177Lu-7E11 in comparison to that of 111In-7E11. Continued accumulation in tumor was observed for the entire time

  12. Formulation, preclinical evaluation, and preliminary clinical investigation of an in-house freeze-dried EDTMP kit suitable for the preparation of 177Lu-EDTMP.

    PubMed

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

    2014-12-01

    The objective of the present work was to develop a freeze-dried ethylenediaminetetramethylene phosphonic acid (EDTMP) kit, suitable for the convenient and single-step preparation of (177)Lu-EDTMP, which is currently being evaluated as a promising radiopharmaceutical for providing palliative care to patients suffering from skeletal metastases and to assess the potential of the agent in human patients. Lyophilized EDTMP kits having identical composition with Quadramet(®) were prepared using EDTMP, NaOH, and anhydrous CaCO3. The (177)Lu-EDTMP patient dose was prepared by incubating the kit materials dissolved in 1 mL of water for injection and (177)LuCl3, produced in-house, at room temperature for 15 minutes. Pharmacokinetic behavior of the agent was studied by carrying out biodistribution and scintigraphic imaging studies in normal Wistar rats. Clinical studies were performed by administering the preparation in patients suffering from disseminated skeletal metastases. Five batches of freeze-dried EDTMP kits with 50 kit vials in each batch were prepared. Each kit vial comprised a lyophilized mixture of 35 mg EDTMP, 14.1 mg NaOH, and 5.8 mg of CaCO3. The (177)Lu-EDTMP complex was prepared with excellent radiochemical purity (>99%) and high stability (>98% until 9 days postpreparation) using these kits. Radiochemical studies showed that this kit could be used within a pH range of 6-9 and with (177)Lu having specific activity as low as 925 GBq · g(-1) (25 Ci · g(-1)) for the preparation of up to 3.7 GBq (100 mCi) of (177)Lu-EDTMP. Biodistribution studies in animals revealed selective accumulation of the agent in skeleton (∼ 60% of the injected activity) with major renal clearance. Preliminary clinical studies in 10 patients exhibited selective accumulation of the radiotracer in skeletal lesions and provided significant pain relief thereby improving the quality of life of the patients. Freeze-dried EDTMP kits, suitable for the preparation of patient doses of (177)Lu

  13. Targeted antisense radiotherapy and dose fractionation using a (177)Lu-labeled anti-bcl-2 peptide nucleic acid-peptide conjugate.

    PubMed

    Liu, Dijie; Balkin, Ethan R; Jia, Fang; Ruthengael, Varyanna C; Smith, C Jeffrey; Lewis, Michael R

    2015-09-01

    The overall goal of these studies was to test the hypothesis that simultaneous down-regulation of a tumor survival gene and delivery of internally emitted cytotoxic radiation will be more effective than either treatment modality alone. The objectives were to evaluate the therapeutic efficacy of a (177)Lu-labeled anti-bcl-2-PNA-Tyr(3)-octreotate antisense conjugate in a mouse model bearing human non-Hodgkin's lymphoma (NHL) tumor xenografts and to optimize targeted antisense radiotherapy by dose fractionation. In the initial therapy studies, tumor-bearing mice were given saline, nonradioactive DOTA-anti-bcl-2-PNA-Tyr(3)-octreotate, (177)Lu-DOTA-Tyr(3)-octreotate, (177)Lu-DOTA-PNA-peptide alone, or (177)Lu-DOTA-PNA-peptide followed by a chase dose of nonradioactive PNA-peptide. The MTD of (177)Lu-DOTA-anti-bcl-2-PNA-Tyr(3)-octreotate was then determined. Subsequently single dose MTD and four weekly fractionated doses were directly compared, followed by histopathologic evaluation. Antisense radiotherapy using 4.44 MBq of the (177)Lu-DOTA-PNA-peptide followed by nonradioactive PNA-peptide was significantly more effective than other low dose treatment regimens. A dose of 18.5 MBq of (177)Lu-DOTA-PNA-peptide was determined to be the approximate maximum tolerated dose (MTD). The median times to progression to a 1cm(3) tumor volume were 32 and 49 days for single dose MTD and fractionated dose (4 × 4.63 MBq) groups, respectively. Histopathology revealed metastases in the single dose groups, but not in the dose fractionation group. Targeted antisense radiotherapy using (177)Lu-DOTA-anti-bcl-2-PNA-Tyr(3)-octreotate and DOTA-PNA-peptide conjugate effectively inhibited tumor progression in a mouse model of NHL. Furthermore, a dose fractionation regimen had a significant advantage over a single high dose, in terms of tumor growth inhibition and prevention of metastasis. Down-regulating bcl-2, an anti-apoptotic proto-oncogene, is a mechanism to reverse chemotherapy resistance or

  14. Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases.

    PubMed

    Thapa, Pradeep; Nikam, Dilip; Das, Tapas; Sonawane, Geeta; Agarwal, Jai Prakash; Basu, Sandip

    2015-10-01

    This prospective study compared 177Lu-ethylene diamine tetramethylene phosphonate (EDTMP) with 153Sm-EDTMP for painful skeletal metastases. Half of the 32 patients were treated with 177Lu-EDTMP and half with 153Sm-EDTMP, at 37 MBq/kg of body weight. Analgesic, pain, and quality-of-life scores (EORTC, Karnofsky, ECOG) and bone proliferation marker were used to examine efficacy. Hematologic toxicity was evaluated using NCI-CTCAE and compared between groups at baseline and each month till 3 mo after therapy. Pain relief was categorized as complete, partial, minimal, or none. Pain relief with 177Lu-EDTMP was 80%: 50% complete, 41.67% partial, and 8.33% minimal. Pain relief with 153Sm-EDTMP was 75%: 33.33% complete, 58.33% partial, and 8.33% minimal. The difference was not significant (P=1.000). Quality of life at 3 mo after therapy improved significantly in both groups as per ECOG score (P=0.014 and 0.005 for 177Lu-EDTMP and 153Sm-EDTMP, respectively), Karnofsky index (P=0.007 and 0.023 for 177Lu-EDTMP and 153Sm-EDTMP, respectively), and EORTC score (P=0.004 and <0.001 for 177Lu-EDTMP and 153Sm-EDTMP, respectively). Bone proliferation marker in responders of both groups dropped significantly (P=0.008 for 177Lu-EDTMP and P=0.019 for 153Sm-EDTMP), parallel to clinical response. For 177Lu-EDTMP, anemia, leukopenia, and thrombocytopenia were nonserious (grade I/II) in 46.67%, 46.67%, and 20%, respectively, and serious (grade III/IV) in 20%, 6.67%, and 0%, respectively. For 153Sm-EDTMP, anemia, leukopenia, and thrombocytopenia were nonserious (grade I/II) in 62.5%, 31.25%, and 18.75%, respectively, and serious (grade III/IV) in 18.75%, 0%, and 6.25%, respectively. One patient treated with 153Sm-EDTMP had grade IV thrombocytopenia but required no blood transfusion. Differences between groups were not significant for either nonserious or serious toxicity. For 177Lu-EDTMP, 3 of 12 responders experienced the flare phenomenon on the third day after therapy and one on the fifth

  15. Dosimetry of [177Lu]-DO3A-VS-Cys40-Exendin-4 – impact on the feasibility of insulinoma internal radiotherapy

    PubMed Central

    Velikyan, Irina; Bulenga, Thomas N; Selvaraju, Ramkumar; Lubberink, Mark; Espes, Daniel; Rosenström, Ulrika; Eriksson, Olof

    2015-01-01

    [68Ga]-DO3A-VS-Cys40-Exendin-4 has been shown to be a promising imaging candidate for targeting glucagon like peptide-1 receptor (GLP-1R). In the light of radiotheranostics and personalized medicine the 177Lu-labelled analogue is of paramount interest. In this study we have investigated the organ distribution of [177Lu]-DO3A-VS-Cys40-Exendin-4 in rat and calculated human dosimetry parameters in order to estimate the maximal acceptable administered radioactivity, and thus potential applicability of [177Lu]-DO3A-VS-Cys40-Exendin-4 for internal radiotherapy of insulinomas. Nine male and nine female Lewis rats were injected with [177Lu]-DO3A-VS-Cys40-Exendin-4 for ex vivo organ distribution study at nine time points. The estimation of human organ/total body absorbed and total effective doses was performed using Organ Level Internal Dose Assessment Code software (OLINDA/EXM 1.1). Six more rats (male: n = 3; female: n = 3) were scanned by single photon emission tomography and computed tomography (SPECT-CT). The renal function and potential cell dysfunction were monitored by creatinine ISTAT and glucose levels. The fine uptake structure of kidney and pancreas was investigated by ex vivo autoradiography. Blood clearance and washout from most of the organs was fast. The kidney was the dose-limiting organ with absorbed dose of 5.88 and 6.04 mGy/MBq, respectively for female and male. Pancreatic beta cells demonstrated radioactivity accumulation. Renal function and beta cell function remained unaffected by radiation. The absorbed dose of [177Lu]-DO3A-VS-Cys40-Exendin-4 to kidneys may limit the clinical application of the agent. However, hypothetically, kidney protection and peptidase inhibition may allow reduction of kidney absorbed dose and amplification of tumour absorbed doses. PMID:25973333

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

    PubMed

    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.

  17. Influence of cations on the complexation yield of DOTATATE with yttrium and lutetium: a perspective study for enhancing the 90Y and 177Lu labeling conditions.

    PubMed

    Asti, Mattia; Tegoni, Matteo; Farioli, Daniela; Iori, Michele; Guidotti, Claudio; Cutler, Cathy S; Mayer, Pat; Versari, Annibale; Salvo, Diana

    2012-05-01

    The DOTA macrocyclic ligand can form stable complexes with many cations besides yttrium and lutetium. For this reason, the presence of competing cationic metals in yttrium-90 and lutetium-177 chloride solutions can dramatically influence the radiolabeling yield. The aim of this study was to evaluate the coordination yield of yttrium- and lutetium-DOTATATE complexes when the reaction is performed in the presence of varying amounts of competing cationic impurities. In the first set of experiments, the preparation of the samples was performed by using natural yttrium and lutetium (20.4 nmol). The molar ratio between DOTATATE and these metals was 1 to 1. Metal competitors (Pb(2+), Zn(2+), Cu(2+), Fe(3+), Al(3+), Ni(2+), Co(2+), Cr(3+)) were added separately to obtain samples with varying molar ratio with respect to yttrium or lutetium (0.1, 0.5, 1, 2 and 10). The final solutions were analyzed through ultra high-performance liquid chromatography with an UV detector. In the second set of experiments, an amount of (90)Y or (177)Lu chloride (6 MBq corresponding to 3.3 and 45 pmol, respectively) was added to the samples, and a radio-thin layer chromatography analysis was carried out. The coordination of Y(3+) and Lu(3+) was dramatically influenced by low levels of Zn(2+), Cu(2+) and Co(2+). Pb(2+) and Ni(2+) were also shown to be strong competitors at higher concentrations. Fe(3+) was expected to be a strong competitor, but the effect on the incorporation was only partly dependent on its concentration. Al(3+) and Cr(3+) did not compete with Y(3+) and Lu(3+) in the formation of DOTATATE complexes. Copyright © 2012 Elsevier Inc. All rights reserved.

  18. Mass selective separation applied to radioisotopes of cesium: Mass selective applied to radioisotopes

    SciTech Connect

    Dion, Michael; Eiden, Greg; Farmer, Orville; Finch, Zach; Liezers, Martin

    2016-07-22

    A developed technique that uses the intrinsic mass-based separation capability of a quadrupole mass spectrometer has been used to resolve spectral radiometric interference of two isotopes of the same element. In this work the starting sample was a combination of 137Cs and 134Cs and was (activity) dominated by 137Cs and this methodology separated and “implanted” 134Cs that was later quantified for spectral features and ac- tivity with traditional radiometric techniques. This work demonstrated a 134Cs/137Cs activity ratio enhancement of >4 orders of magnitude and complete removal of 137Cs spectral features from the implanted target mass (i.e., 134).

  19. Bone marrow dosimetry in peptide receptor radionuclide therapy with [177Lu-DOTA(0),Tyr(3)]octreotate.

    PubMed

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

    2009-07-01

    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<0.001). No correlation between the calculated absorbed dose in the bone marrow and the change in platelets was found. There was a considerable contribution from other organs and the remainder of the body to the bone marrow absorbed dose. (1) After PRRT with [(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

  20. 177Lu-DO3A-HSA-Z EGFR:1907: characterization as a potential radiopharmaceutical for radionuclide therapy of EGFR-expressing head and neck carcinomas.

    PubMed

    Hoppmann, Susan; Qi, Shibo; Miao, Zheng; Liu, Hongguang; Jiang, Han; Cutler, Cathy S; Bao, Ande; Cheng, Zhen

    2012-06-01

    Epidermal growth factor receptor 1 (EGFR) is an attractive target for radionuclide therapy of head and neck carcinomas. Affibody molecules against EGFR (Z(EGFR)) show excellent tumor localizations in imaging studies. However, one major drawback is that radiometal-labeled Affibody molecules display extremely high uptakes in the radiosensitive kidneys which may impact their use as radiotherapeutic agents. The purpose of this study is to further explore whether radiometal-labeled human serum albumin (HSA)-Z(EFGR) bioconjugates display desirable profiles for the use in radionuclide therapy of EGFR-positive head and neck carcinomas. The Z(EFGR) analog, Ac-Cys-Z(EGFR:1907), was site-specifically conjugated with HSA. The resulting bioconjugate 1,4,7,10-tetraazacyclododecane-1,4,7-triacetic acid (DO3A)-HSA-Z(EGFR:1907) was then radiolabeled with either (64)Cu or (177)Lu and subjected to in vitro cell uptake and internalization studies using the human oral squamous carcinoma cell line SAS. Positron emission tomography (PET), single photon emission computed tomography (SPECT), and biodistribution studies were conducted using SAS-tumor-bearing mice. Cell studies revealed a high (8.43 ± 0.55 % at 4 h) and specific (0.95 ± 0.09 % at 4 h) uptake of (177)Lu-DO3A-HSA-Z(EGFR:1907) as determined by blocking with nonradioactive Z(EGFR:1907). The internalization of (177)Lu-DO3A-HSA-Z(EGFR:1907) was verified in vitro and found to be significantly higher than that of (177)Lu-labeled Z(EFGR) at 2-24 h of incubation. PET and SPECT studies showed good tumor imaging contrasts. The biodistribution of (177)Lu-DO3A-HSA-Z(EGFR:1907) in SAS-tumor-bearing mice displayed high tumor uptake (5.1 ± 0.44 % ID/g) and liver uptake (31.5 ± 7.66 % ID/g) and moderate kidney uptake (8.5 ± 1.08 % ID/g) at 72 h after injection. (177)Lu-DO3A-HSA-Z(EGFR:1907) shows promising in vivo profiles and may be a potential radiopharmaceutical for radionuclide therapy of EGFR-expressing head and neck carcinomas.

  1. DOTA conjugate with an albumin-binding entity enables the first folic acid-targeted 177Lu-radionuclide tumor therapy in mice.

    PubMed

    Müller, Cristina; Struthers, Harriet; Winiger, Christian; Zhernosekov, Konstantin; Schibli, Roger

    2013-01-01

    The folate receptor (FR) has proven a valuable target for nuclear imaging using folic acid radioconjugates. However, using folate-based radiopharmaceuticals for therapy has long been regarded as an unattainable goal because of their considerable renal accumulation. Herein, we present a novel strategy in which a DOTA-folate conjugate with an albumin-binding entity (cm09) was designed with the aim of prolonging circulation in the blood and therewith potentially improving tumor-to-kidney ratios. The folate conjugate cm09 was radiolabeled with (177)LuCl(3), and stability experiments were performed in plasma. Cell uptake studies were performed on FR-positive KB tumor cells, and an ultrafiltration assay was used to determine the plasma protein-binding properties of (177)Lu-cm09. In vivo, (177)Lu-cm09 was tested in KB tumor-bearing mice using SPECT/CT. The therapeutic anticancer effect of (177)Lu-cm09 (20 MBq) applied as a single injection or as fractionated injections was investigated in different groups of mice (n = 5) by monitoring tumor size and the survival time of treated mice, compared with untreated controls. Compound cm09 was radiolabeled at a specific activity of 40 MBq/nmol, a radiochemical yield of more than 98%, and a stability of more than 99% over 5 d in plasma. Ultrafiltration revealed significant binding of (177)Lu-cm09 to serum proteins (∼91%) in plasma, compared with folate radioconjugate without an albumin-binding entity. Cell uptake and internalization of (177)Lu-cm09 was FR-specific and comparable to other folate radioconjugates. In vivo studies resulted in high tumor uptake (17.56 percentage injected dose per gram [%ID/g] at 4 h after injection), which was almost completely retained for at least 72 h. Renal accumulation was significantly reduced (28 %ID/g at 4 h after injection), compared with folate conjugates that lack an albumin-binding entity (∼70 %ID/g at 4 h after injection). These circumstances enabled SPECT imaging of excellent quality

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2015-01-01

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

  4. Experimental limits for heavy neutrino admixture deduced from 177Lu β decay and constraints on the life time of a radiative neutrino decay mode

    NASA Astrophysics Data System (ADS)

    Schönert, S.; Oberauer, L.; Hagner, C.; Feilitzsch, F. v.; Schreckenbach, K.; Declais, Y.; Mayerhofer, U.

    1996-05-01

    From cosmological constraints, the requirement for stable neutrinos is to have masses less than 30 eV. In the case that neutrino masses exceed this bound, neutrinos must decay sufficiently fast in order to satisfy the presently observed energy density of the universe. The experiments presented in this contribution consist of the complementary search for heavy neutrino admixture in nuclear beta decay of 177Lu and of the search for a radiative neutrino decay mode at the nuclear power station in Bugey, France. The data obtained from the 177Lu beta decay restrict the mixing probability of a heavy neutrino to the electron | U eh| 2 < 0.2 - 0.3% (90% Cl) for neutrino masses between 10 and 95 keV. The radiative lifetime is constrained to exceed t/ m > 180 × | U eh| 2 sec/eV which is one order of magnitude more restrictive than previous laboratory limits.

  5. Up-regulation of somatostatin receptor density on rat CA20948 tumors escaped from low dose [177Lu-DOTA0,Tyr3]octreotate therapy.

    PubMed

    Melis, M; Forrer, F; Capello, A; Bijster, M; Bernard, B F; Reubi, J C; Krenning, E P; De Jong, M

    2007-12-01

    Peptide receptor radionuclide therapy using the somatostatin analogue [(177)Lu-DOTA(0),Tyr(3)]octreotate is a convincing treatment modality for metastasized neuroendocrine tumors. Therapeutic doses are administered in 4 cycles with 6-10 week intervals. A high somatostatin receptor density on tumor cells is a prerequisite at every administration to enable effective therapy. In this study, the density of the somatostatin receptor subtype 2 (sst2) was investigated in the rat CA20948 pancreatic tumor model after low dose [(177)Lu-DOTA(0), Tyr(3)]octreotate administration resulting in approximately 20 Gy tumor radiation absorbed dose, whereas 60 Gy is needed to induce complete tumor regression in these and the majority of tumors. Sixteen days after inoculation of the CA20948 tumor, male Lewis rats were injected with 185 MBq [(177)Lu-DOTA(0),Tyr(3)]octreotate to initiate a decline in tumor size. Approximately 40 days after injection, tumors re-grew progressively after initial response. Quantification of sst2 expression was performed using in vitro autoradiography on frozen sections of three groups: control (not-treated) tumors, tumors in regression and tumors in re-growth. Histology and proliferation were determined using HE- and anti-Ki-67-staining. The sst2 expression on CA20948 tumor cells decreased significantly after therapy to 5% of control level. However, tumors escaping from therapy showed an up-regulated sst2 level of 2-5 times higher sst2 density compared to control tumors. After a suboptimal therapeutic dose of [(177)Lu-DOTA(0),Tyr(3)]octreotate, escape of tumors is likely to occur. Since these cells show an up-regulated sst2 receptor density, a next therapeutic administration of radiolabelled sst2 analogue can be expected to be highly effective.

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

    SciTech Connect

    Montégiani, Jean-François; Gaudin, Émilie; Després, Philippe; Jackson, Price A.; Beauregard, Jean-Mathieu

    2014-08-15

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

  7. Method for sequential injection of liquid samples for radioisotope separations

    DOEpatents

    Egorov, Oleg B.; Grate, Jay W.; Bray, Lane A.

    2000-01-01

    The present invention is a method of separating a short-lived daughter isotope from a longer lived parent isotope, with recovery of the parent isotope for further use. Using a system with a bi-directional pump and one or more valves, a solution of the parent isotope is processed to generate two separate solutions, one of which contains the daughter isotope, from which the parent has been removed with a high decontamination factor, and the other solution contains the recovered parent isotope. The process can be repeated on this solution of the parent isotope. The system with the fluid drive and one or more valves is controlled by a program on a microprocessor executing a series of steps to accomplish the operation. In one approach, the cow solution is passed through a separation medium that selectively retains the desired daughter isotope, while the parent isotope and the matrix pass through the medium. After washing this medium, the daughter is released from the separation medium using another solution. With the automated generator of the present invention, all solution handling steps necessary to perform a daughter/parent radionuclide separation, e.g. Bi-213 from Ac-225 "cow" solution, are performed in a consistent, enclosed, and remotely operated format. Operator exposure and spread of contamination are greatly minimized compared to the manual generator procedure described in U.S. patent application Ser. No. 08/789,973, now U.S. Pat. No. 5,749,042, herein incorporated by reference. Using 16 mCi of Ac-225 there was no detectable external contamination of the instrument components.

  8. 177Lu-octreotate, alone or with radiosensitising chemotherapy, is safe in neuroendocrine tumour patients previously treated with high-activity 111In-octreotide.

    PubMed

    Hubble, Daniel; Kong, Grace; Michael, Michael; Johnson, Val; Ramdave, Shakher; Hicks, Rodney John

    2010-10-01

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

  9. A simple and selective method for the separation of Cu radioisotopes from nickel.

    PubMed

    Fan, Xianfeng; Parker, David J; Smith, Mike D; Ingram, Andy; Yang, Zhufang; Seville, Jonathan P K

    2006-10-01

    Separation of copper radioisotopes from a nickel target is normally performed using solvent extraction or anion exchange rather than using cationic exchange. A commonly held opinion is that cationic exchangers have very similar thermodynamic complexation constants for metallic ions with identical charges, therefore making the separation very difficult or impossible. The results presented in this article indicate that the selectivity of Chelex-100 (a cationic ion exchanger) for Cu radioisotope and Ni ions not only depends on the thermodynamic complexation constant in the resin but also markedly varies with the concentration of mobile H+. In our developed method, separation of copper radioisotopes from a nickel target was fulfilled in a column filled with Chelex-100 via controlling the HNO3 concentration of the eluent, and the separation is much more effective, simple and economical in comparison with the common method of anion exchange. For an irradiated nickel target with 650 mg Ni, after separation, the loss of Cu radioisotopes in the nickel portion was reduced from 30% to 0.33% of the total initial radioactivity and the nickel mixed into the radioactive products was reduced from 9.5 to 0.5 mg. This significant improvement will make subsequent labeling much easier and reduce consumption of chelating agents and other chemicals during labeling. If the labeled agent is used in human medical applications, the developed method will significantly decrease the uptake of Ni and chelating agents by patients, therefore reducing both the stress on human body associated with clearing the chemicals from blood and tissue and the risk of various types of acute and chronic disorder due to exposure to Ni.

  10. Peptide receptor radionuclide therapy (PRRT) with [177Lu-DOTA0,Tyr3]octreotate in combination with RAD001 treatment: further investigations on tumor metastasis and response in the rat pancreatic CA20948 tumor model

    PubMed Central

    2014-01-01

    Background Previously, we reported on the unexpected development of distant metastases in the subcutaneous rat pancreas CA20948 tumor model after 4.5 weeks of treatment with RAD001-only or in combination with [177Lu-DOTA0,Tyr3]octreotate (177Lu-DOTATATE) (Cancer Res. 73:12-8, 2013). Moreover, the combination therapy was less effective compared to 177Lu-DOTATATE-only. In the current study, we address the following questions: (1) Why was the combination therapy less effective? Is 177Lu-DOTATATE tumor uptake affected by pretreatment with RAD001? (2) Could sudden cessation of RAD001 therapy cause the development of distant metastases? (3) Is 177Lu-DOTATATE an effective treatment option for these metastases? Methods Lewis rats (HanHsd or SsNHsd substrain with a slight difference in immune response) bearing subcutaneous CA20948 tumors were treated with either 125 or 275 MBq 177Lu-DOTATATE, RAD001, or their combination. RAD001 was given twice a week for 4.5 or 12 weeks, whereas 177Lu-DOTATATE was given as a single injection. When combined, RAD001 was started either 3 days prior to or 3 days post administration of 177Lu-DOTATATE. SPECT/CT was performed to quantify 177Lu-DOTATATE tumor uptake. Where indicated, primary tumors were surgically removed when tumor size is >6,000 mm3 to enable monitoring for possible metastasis. If metastases were suspected, an 111In-DTPA-octreotide SPECT/CT scan was performed. Seven rats with metastases were treated with 400 MBq 177Lu-DOTATATE. Results Lu-DOTATATE tumor uptake was not significantly affected by RAD001 pretreatment. The occurrence of metastases after RAD001 treatment was not dose dependent in the dose range tested, nor was it related to the duration of RAD001 treatment. In the experiment in which the LEW/SsNsd substrain was used, only 12.5% of RAD001-treated rats showed complete response (CR), compared to 50% tumor regression in the control group. Re-treatment with a high dose of 177Lu-DOTATATE resulted in CR in only two

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

    PubMed Central

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

    2016-01-01

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

  12. Effectiveness of radiolabelled somatostatin analogues ((90)Y-DOTATOC and (177)Lu-DOTATATE) in patients with metastatic neuroendocrine tumours: a single centre experience in Mexico.

    PubMed

    Medina-Ornelas, S S; García-Pérez, F O

    To determine the effectiveness of therapy with the radiolabelled somatostatin analogues, (90)Y-DOTATOC and (177)Lu-DOTATATE, in the treatment of metastatic neuroendocrine tumours with progression to first-line treatment. A study was conducted on 30 patients diagnosed with neuroendocrine tumours (gastroenteropancreatic, bronchopulmonary, MEN2A, MEN2B, phaeochromocytoma, and paraganglioma) with metastatic disease diagnosed by the pathology department, with progression to first-line treatment, and recruited from December 2014 to February 2016. Efficacy was analysed using computed tomography (CT) according RECIST 1.1 criteria, and the molecular changes using the SUVmax of PET/CT with (68)Ga-DOTATOC. Safety was carried out with a renal scan with (99m)Tc-MAG3. The 30 patients received a total of 49 cycles (90)Y-DOTATOC (21 doses) and (177) Lu-DOTATATE (28 doses), with a mean of 1.5 cycles per patient. Of these, 17 (56.7%) showed a partial morphological response, 22 (73.3%) molecular and biochemical response, and 23 (76.6%) clinical response. One patient died during the median follow-up of 13 months. The median overall survival from diagnosis was 54 months (95% CI; 31.18-76.81), and median progression-free survival was 32 months (95% CI; 15.00-48.99). Therapy with (90)Y-DOTATOC and (177)Lu-DOTATATE is a promising therapy for patients with well and moderately differentiated neuroendocrine tumours. The efficacy is better the larger the number of cycles administered, inversely proportional to the number of metastases (<10), and is associated with the level of uptake according to the SUVmax by the metastases, regardless of metabolically active tumour volume. Copyright © 2016 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

  13. Multimodal Somatostatin Receptor Theranostics Using [(64)Cu]Cu-/[(177)Lu]Lu-DOTA-(Tyr(3))octreotate and AN-238 in a Mouse Pheochromocytoma Model.

    PubMed

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

    2016-01-01

    Pheochromocytomas and extra-adrenal paragangliomas (PHEO/PGLs) are rare catecholamine-producing chromaffin cell tumors. For metastatic disease, no effective therapy is available. Overexpression of somatostatin type 2 receptors (SSTR2) in PHEO/PGLs promotes interest in applying therapies using somatostatin analogs linked to radionuclides and/or cytotoxic compounds, such as [(177)Lu]Lu-DOTA-(Tyr(3))octreotate (DOTATATE) and AN-238. Systematic evaluation of such therapies for the treatment of PHEO/PGLs requires sophisticated animal models. In this study, the mouse pheochromocytoma (MPC)-mCherry allograft model showed high tumor densities of murine SSTR2 (mSSTR2) and high tumor uptake of [(64)Cu]Cu-DOTATATE. Using tumor sections, we assessed mSSTR2-specific binding of DOTATATE, AN-238, and somatostatin-14. Therapeutic studies showed substantial reduction of tumor growth and tumor-related renal monoamine excretion in tumor-bearing mice after treatment with [(177)Lu]Lu-DOTATATE compared to AN-238 and doxorubicin. Analyses did not show agonist-dependent receptor downregulation after single mSSTR2-targeting therapies. This study demonstrates that the MPC-mCherry model is a uniquely powerful tool for the preclinical evaluation of SSTR2-targeting theranostic applications in vivo. Our findings highlight the therapeutic potential of somatostatin analogs, especially of [(177)Lu]Lu-DOTATATE, for the treatment of metastatic PHEO/PGLs. Repeated treatment cycles, fractionated combinations of SSTR2-targeting radionuclide and cytotoxic therapies, and other adjuvant compounds addressing additional mechanisms may further enhance therapeutic outcome.

  14. Radiolabeling of monoclonal anti-vascular endothelial growth factor receptor 1 (VEGFR 1) with (177)Lu for potential use in radioimmunotherapy.

    PubMed

    Lee, So-Young; Hong, Young-Don; Pyun, Mi-Sun; Felipe, Penelope M; Choi, Sun-Ju

    2009-01-01

    The main goal of this study was to optimize the radioimmunoconjugation of monoclonal anti-vascular endothelial growth factor receptor 1 (VEGFR 1) with (177)Lu as a potential angiogenic molecular tracer for radioimmunotherapy (RIT). For a successful radiolabeling, we chose cysteine derivative DTPA-NCS as the bifunctional chelating agent and optimized radiolabeling condition with modifications on the factors such as the reaction time and molar ratio which are known to be very critical in radiolabeling. Under the optimized conditions, radiolabeling yield was greater than 99%. Immunoactivity of the radioimmunoconjugate was investigated using combinations of radioanalytical and bioanalytical techniques (ITLC-SG, Cyclone phosphorimager, and SDS-PAGE). For biological evaluations we carried out the cell binding assay and biodistribution study using mice bearing Calu6 non-small cell lung cancer xenografts. The biodistribution study showed high specificity in accumulating in tumor tissues where the tumor-to-blood ratio was 3.25:1 24h post-injection. In conclusion, the anti-VEGFR1 monoclonal antibody for angiogenesis targeting was effectively radioconjugated with (177)Lu. This radioimmunoconjugate is applicable to detect of angiogenesis sites in various diseases and treat tumors overexpressing VEGFR 1.

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

    PubMed

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

    2016-10-28

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

  16. Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects.

    PubMed

    Bhardwaj, R; van der Meer, A; Das, S K; de Bruin, M; Gascon, J; Wolterbeek, H T; Denkova, A G; Serra-Crespo, P

    2017-03-13

    (177)Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β(-) emission results in very efficient energy deposition in small-size tumours. Because of this, (177)Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, (177m)Lu and (177)Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The (177m)Lu/(177)Lu radionuclide generator provides a new production route for the therapeutic radionuclide (177)Lu and can bring significant growth in the research and development of (177)Lu based pharmaceuticals.

  17. Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects

    PubMed Central

    Bhardwaj, R.; van der Meer, A.; Das, S. K.; de Bruin, M.; Gascon, J.; Wolterbeek, H. T.; Denkova, A. G.; Serra-Crespo, P.

    2017-01-01

    177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β− emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals. PMID:28287131

  18. Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects

    NASA Astrophysics Data System (ADS)

    Bhardwaj, R.; van der Meer, A.; Das, S. K.; de Bruin, M.; Gascon, J.; Wolterbeek, H. T.; Denkova, A. G.; Serra-Crespo, P.

    2017-03-01

    177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β‑ emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals.

  19. Biological comparison of 149Pm-, 166Ho-, and 177Lu-DOTA-biotin pretargeted by CC49 scFv-streptavidin fusion protein in xenograft-bearing nude mice.

    PubMed

    Lewis, Michael R; Zhang, Jiuli; Jia, Fang; Owen, Nellie K; Cutler, Cathy S; Embree, Mary F; Schultz, Jody; Theodore, Louis J; Ketring, Alan R; Jurisson, Silvia S; Axworthy, Donald B

    2004-02-01

    The radiolanthanides (149)Pm, (166)Ho, and (177)Lu possess a range of half-lives and alpha(-) beta(-) energies for targeted radiotherapy of cancer. (149)Pm-, (166)Ho-, and (177)Lu-DOTA-biotin were pretargeted to LS174T colorectal tumors in nude mice with CC49 scFvSA antibody-streptavidin fusion protein. Tumor uptakes of (149)Pm (22.9% ID/g), (166)Ho (30.2% ID/g), and (177)Lu (35.4% ID/g) peaked at 1-4 h. Rapid blood disappearance was accompanied by urinary excretion of 59-66% ID within 1 h. Biodistributions of these agents show promise for pretargeted radioimmunotherapy of cancer.

  20. Multifunctional targeted therapy system based on (99m) Tc/(177) Lu-labeled gold nanoparticles-Tat(49-57)-Lys(3) -bombesin internalized in nuclei of prostate cancer cells.

    PubMed

    Jiménez-Mancilla, Nallely; Ferro-Flores, Guillermina; Santos-Cuevas, Clara; Ocampo-García, Blanca; Luna-Gutiérrez, Myrna; Azorín-Vega, Erika; Isaac-Olivé, Keila; Camacho-López, Miguel; Torres-García, Eugenio

    2013-11-01

    Radiolabeled gold nanoparticles may function simultaneously as radiotherapy and thermal ablation systems. The gastrin-releasing peptide receptor (GRP-r) is overexpressed in prostate cancer, and Lys(3) -bombesin is a peptide that binds with high affinity to the GRP-r. HIV Tat(49-57) is a cell-penetrating peptide that reaches the DNA. In cancer cells, (177) Lu shows efficient crossfire effect, whereas (99m) Tc that is internalized in the cancer cell nuclei acts as an effective system of targeted radiotherapy because of the biological Auger effect. The aim of this research was to evaluate the in vitro potential of (99m) Tc-labeled and (177) Lu-labeled gold nanoparticles conjugated to Tat(49-57)-Lys(3) -bombesin peptides ((99m) Tc/(177) Lu-AuNP-Tat-BN) as a plasmonic photothermal therapy and targeted radiotherapy system in PC3 prostate cancer cells. Peptides were conjugated to AuNPs (5 nm) by spontaneous reaction with the thiol group of cysteine (Cys). The effect on PC3 cell viability after laser heating of the AuNP-Tat-BN incubated with the cancer cells was conducted using an Nd:YAG laser pulsed for 5 ns at 532 nm (0.65 W/cm(2) ). For the (99m) Tc/(177) Lu-AuNP-Tat-BN to be obtained, the (177) Lu-DOTA-Gly-Gly-Cys and (99m) Tc-HYNIC-octreotide radiopeptides were first prepared and added simultaneously to a solution of AuNP-Tat-BN. (99m) Tc/(177) Lu-AuNP-Tat-BN (20 Bq/cell) was incubated with PC3 cells, and the effect on the cell proliferation was evaluated after 3 days. Fluorescence images of (99m) Tc/(177) Lu-AuNP-Tat-BN internalized in nuclei of PC3 were also obtained. After laser irradiation, the presence of AuNP-Tat-BN caused a significant increase in the temperature of the medium (46.4 vs 39.5 °C of that without AuNP) resulting in a significant decrease in PC3 cell viability down to 1.3%. After treatment with (99m) Tc/(177) Lu-AuNP-Tat-BN, the PC3 cell proliferation was inhibited. The nanosystem exhibited properties suitable for plasmonic

  1. Comparative analysis of 11 different radioisotopes for palliative treatment of bone metastases by computational methods

    SciTech Connect

    Guerra Liberal, Francisco D. C. E-mail: adriana-tavares@msn.com; Tavares, Adriana Alexandre S. E-mail: adriana-tavares@msn.com; Tavares, João Manuel R. S.

    2014-11-01

    Purpose: Throughout the years, the palliative treatment of bone metastases using bone seeking radiotracers has been part of the therapeutic resources used in oncology, but the choice of which bone seeking agent to use is not consensual across sites and limited data are available comparing the characteristics of each radioisotope. Computational simulation is a simple and practical method to study and to compare a variety of radioisotopes for different medical applications, including the palliative treatment of bone metastases. This study aims to evaluate and compare 11 different radioisotopes currently in use or under research for the palliative treatment of bone metastases using computational methods. Methods: Computational models were used to estimate the percentage of deoxyribonucleic acid (DNA) damage (fast Monte Carlo damage algorithm), the probability of correct DNA repair (Monte Carlo excision repair algorithm), and the radiation-induced cellular effects (virtual cell radiobiology algorithm) post-irradiation with selected particles emitted by phosphorus-32 ({sup 32}P), strontium-89 ({sup 89}Sr), yttrium-90 ({sup 90}Y ), tin-117 ({sup 117m}Sn), samarium-153 ({sup 153}Sm), holmium-166 ({sup 166}Ho), thulium-170 ({sup 170}Tm), lutetium-177 ({sup 177}Lu), rhenium-186 ({sup 186}Re), rhenium-188 ({sup 188}Re), and radium-223 ({sup 223}Ra). Results: {sup 223}Ra alpha particles, {sup 177}Lu beta minus particles, and {sup 170}Tm beta minus particles induced the highest cell death of all investigated particles and radioisotopes. The cell survival fraction measured post-irradiation with beta minus particles emitted by {sup 89}Sr and {sup 153}Sm, two of the most frequently used radionuclides in the palliative treatment of bone metastases in clinical routine practice, was higher than {sup 177}Lu beta minus particles and {sup 223}Ra alpha particles. Conclusions: {sup 223}Ra and {sup 177}Lu hold the highest potential for palliative treatment of bone metastases of all

  2. Response and Tolerability of a Single Dose of 177Lu-PSMA-617 in Patients with Metastatic Castration-Resistant Prostate Cancer: A Multicenter Retrospective Analysis.

    PubMed

    Rahbar, Kambiz; Schmidt, Matthias; Heinzel, Alexander; Eppard, Elisabeth; Bode, Axel; Yordanova, Anna; Claesener, Michael; Ahmadzadehfar, Hojjat

    2016-09-01

    Radiolabeled prostate-specific membrane antigen (PSMA) ligands represent a true theranostic concept for diagnosis and therapy in patients with relapsed or metastatic prostate cancer. The aim of this study was to evaluate the response to and tolerability of a single dose of (177)Lu-PSMA-617 in a large cohort of patients with metastatic castration-resistant prostate cancer (mCRPC). The data of 82 consecutive patients (median age, 73 y; range, 43-87 y) with mCRPC who received a single dose of (177)Lu-PSMA-617 (mean, 5.9 ± 0.5 GBq) were retrospectively analyzed. Data were collected at baseline and 8 wk after therapy. (68)Ga-PSMA-11 PET/CT was performed on all patients to verify sufficient PSMA expression. Bone, lymph node, liver, and lung metastases were present in 99%, 65%, 17%, and 11% of the patients, respectively. Tolerability and response were evaluated using hematologic parameters, renal scintigraphy, clinical data, and the prostate-specific antigen (PSA) level at baseline and 8 wk after therapy application. Six patients died, and 2 patients dropped out because they were not willing to continue therapy and follow-up. The complete dataset of 74 patients was available for analysis. Forty-seven patients (64%) showed a PSA decline, including 23 (31%) with a decline by more than 50%. Thirty-five patients (47%) had stable disease: the change in their PSA level ranged from less than a 50% decline to less than a 25% rise. Seventeen patients (23%) had progressive disease: their PSA level rose by more than 25%. There were no significant changes in hemoglobin, white blood cells, creatinine, or tubular extraction rates indicative of toxicity. There was a significant but mild decrease in platelets, but the median value was still within the reference range. This retrospective multicenter analysis suggests that radioligand therapy with (177)Lu-PSMA-617 is safe and well tolerated and has a considerable effect on PSA level. Therefore, it offers an additional therapeutic option

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

    PubMed Central

    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

  4. Evaluation of Beta-Absorbed Fractions in a Mouse Model for 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177Lu Radionuclides

    SciTech Connect

    Miller, William H.; Hartmann-Siantar, Christine; Fisher, Darrell R.; Descalle, Marie-Anne; Daly, Tom; Lehmann, Joerg; Lewis, Michael R.; Hoffman, Timothy J.; Smith, Jeff; Situ, Peter D.; Volkert, Wynn A.

    2005-08-01

    Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular-targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177 Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for 90Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for 90Y to 1% for 177Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable.

  5. 177 Lu-Labeled Phosphoramidate-Based PSMA Inhibitors: The Effect of an Albumin Binder on Biodistribution and Therapeutic Efficacy in Prostate Tumor-Bearing Mice

    DOE PAGES

    Choy, Cindy J.; Ling, Xiaoxi; Geruntho, Jonathan J.; ...

    2017-04-27

    Prostate-specific membrane antigen (PSMA) continues to be an active biomarker for small-molecule PSMA-targeted imaging and therapeutic agents for prostate cancer and various non-prostatic tumors that are characterized by PSMA expression on their neovasculature. One of the challenges for small-molecule PSMA inhibitors with respect to delivering therapeutic payloads is their rapid renal clearance. In order to overcome this pharmacokinetic challenge, we outfitted a 177Lu-labeled phosphoramidate-based PSMA inhibitor (CTT1298) with an albumin-binding motif (CTT1403) and compared its in vivo performance with that of an analogous compound lacking the albumin-binding motif (CTT1401). The radiolabeling of CTT1401 and CTT1403 was achieved using click chemistrymore » to connect 177Lu-DOTA-N3 to the dibenzocyclooctyne (DBCO)-bearing CTT1298 inhibitor cores. A direct comparison in vitro and in vivo performance was made for CTT1401 and CTT1403; the specificity and efficacy by means of cellular uptake and internalization, biodistribution, and therapeutic efficacy were determined for both compounds. And while both compounds displayed excellent uptake and rapid internalization in PSMA+ PC3-PIP cells, the albumin binding moiety in CTT1403 conferred clear advantages to the PSMA-inhibitor scaffold including increased circulating half-life and prostate tumor uptake that continued to increase up to 168 h post-injection. This then increased tumor uptake translated into superior therapeutic efficacy of CTT1403 in PSMA+ PC3-PIP human xenograft tumors.« less

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

    PubMed Central

    Thakral, Parul; Singla, Suhas; Yadav, Madhav Prasad; Vasisht, Atul; Sharma, Atul; Gupta, Santosh Kumar; Bal, C.S.; Snehlata; Malhotra, Arun

    2014-01-01

    Background & objectives: The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Methods: Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. Results: An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim). The radiochemical purity of the labelled antibody was > 95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. Interpretation & conclusions: A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma can be considered. PMID:24927340

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

    PubMed

    Thakral, Parul; Singla, Suhas; Yadav, Madhav Prasad; Vasisht, Atul; Sharma, Atul; Gupta, Santosh Kumar; Bal, C S; Malhotra, Arun

    2014-04-01

    The prerequisite of radioimmunotherapy is stable binding of a radionuclide to monoclonal antibodies, which are specific to the tumour-associated antigen. Most B-cell lymphomas express CD20 antigen on the surface of the tumour cells, making it a suitable target for therapeutic radioactive monoclonal antibodies. In the present study, the immunoconjugate of biosimilar Rituximab (Reditux™) and macrocyclic chelator, p-SCN-Bz-DOTA, was prepared and radiolabelled with Lutetium-177 followed by quality control procedures. Rituximab(BioSim) was desalted with sodium bicarbonate (0.1M, pH 9.0) and incubated with DOTA-SCN (1:50). The effectiveness of the conjugation was evaluated by determining the number of chelators per antibody molecule. This conjugate was radiolabelled with Lutetium-177 and purified using PD10 column. The quality control parameters like pH, clarity, radiochemical purity, in vitro stability and sterility were studied. Immunoreactivity of 177 Lu-DOTA-Rituximab (BioSim) was assessed using RAMOS cells. The radioimmunoconjugate (RIC) after stringent quality assurance was injected in three patients and the biodistribution profile was analysed. An average of 4.25 ± 1.04 p-SCN-Bz-DOTA molecules could be randomly conjugated to a single molecule of Rituximab (BioSim).The radiochemical purity of the labelled antibody was > 95 per cent with preserved affinity for CD20 antigen. The final preparation was stable up to about 120 h when tested under different conditions. A favourable biodistribution profile was observed with liver showing the maximum uptake of the RIC. A favourable radiochemical purity, stability and biodistribution of the radiolabelled immunoconjugate indicate that clinical trials for evaluation of toxicity and efficacy of 177 Lu-DOTA-antiCD20 antibody-Rituximab (BioSim) in patients of relapsed and refractory non Hodgkin's lymphoma can be considered.

  8. Evaluation of beta-absorbed fractions in a mouse model for 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177Lu radionuclides.

    PubMed

    Miller, William H; Hartmann-Siantar, Christine; Fisher, Darrell; Descalle, Marie-Anne; Daly, Tom; Lehmann, Joerg; Lewis, Michael R; Hoffman, Timothy; Smith, Jeff; Situ, Peter D; Volkert, Wynn A

    2005-08-01

    Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular- targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing (90)Y, (188)Re, (166)Ho, (149)Pm, (64)Cu, and (177)Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for (90)Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% for the worst-case organ with average differences (averaged over all organs) decreasing from 5% for (90)Y to 1% for (177)Lu. When used with typical biodistribution data, the three different models predict doses that are in agreement to within 5% for the worst-case organ. The beta-absorbed fractions and cross-organ-deposited energy provided in this paper can be used by researchers to predict mouse-organ doses and should contribute to an improved understanding of the relationship between dose and radiation toxicity in mouse models where use of these isotopes is favorable.

  9. Dosimetric evaluation of 153Sm-EDTMP, 177Lu-EDTMP and 166Ho-EDTMP for systemic radiation therapy: Influence of type and energy of radiation and half-life of radionuclides

    NASA Astrophysics Data System (ADS)

    Ranjbar, Hassan; Ghannadi-Maragheh, Mohammad; Bahrami-Samani, Ali; Beiki, Davood

    2015-03-01

    In radiopharmaceutical therapy, delivered doses to critical organs must be below a certain threshold therefore internal radiation dosimetry of radiopharmaceuticals is essential. Advantages and disadvantages of radionuclides with different characteristics were evaluated for selection of appropriate radionuclide. The Monte Carlo MCNPX simulation program was used to obtain radial dose and cumulative dose of 153Sm, 177Lu and 166Ho used in radiotherapy of bone metastases. A cylindrical geometry with constant density materials was supposed for simulation of femur bone. The radius of bone marrow, bone, and surrounding soft tissue was considered 0.6 cm, 1.3 cm and 4 cm, respectively. It was assumed that the radionuclides were uniformly distributed throughout the tumor. "continuous energy spectrum" of beta particle was used instead of mean beta energy. Our simulations show that absorbed dose in target organ (bone) is greater than other organs and 166Ho gives a higher dose to the critical organ of bone marrow than either 153Sm or 177Lu. Absorbed dose versus time demonstrate faster dose delivery for the short half-life radionuclides (153Sm and 166Ho). These results are in good agreement with clinical observations which show a pain relief within 1 week after intravenous administration of 153Sm-EDTMP, whereas it occurs within 2 week in the case of 177Lu-EDTMP. According to the results, combination of different radionuclides with different characteristics such as 153Sm-EDTMP and 177Lu-EDTMP could be more advantageous to patients with painful bone metastasis.

  10. Radiation Dosimetry for (177)Lu-PSMA I&T in Metastatic Castration-Resistant Prostate Cancer: Absorbed Dose in Normal Organs and Tumor Lesions.

    PubMed

    Okamoto, Shozo; Thieme, Anne; Allmann, Jakob; D'Alessandria, Calogero; Maurer, Tobias; Retz, Margitta; Tauber, Robert; Heck, Matthias M; Wester, Hans-Juergen; Tamaki, Nagara; Fendler, Wolfgang P; Herrmann, Ken; Pfob, Christian H; Scheidhauer, Klemens; Schwaiger, Markus; Ziegler, Sibylle; Eiber, Matthias

    2017-03-01

    Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy is increasingly used in metastatic castration-resistant prostate cancer. We aimed to estimate the absorbed doses for normal organs and tumor lesions using (177)Lu-PSMA I&T (I&T is imaging and therapy) in patients undergoing up to 4 cycles of radioligand therapy. Results were compared with pretherapeutic Glu-NH-CO-NH-Lys-(Ahx)-[(68)Ga(HBEDCC)] ((68)Ga-PSMA-HBED-CC) PET. Methods: A total of 34 cycles in 18 patients were analyzed retrospectively. In 15 patients the first, in 9 the second, in 5 the third, and in 5 the fourth cycle was analyzed, respectively. Whole-body scintigraphy was performed at least between 30-120 min, 24 h, and 6-8 d after administration. Regions of interest covering the whole body, organs, and up to 4 tumor lesions were drawn. Organ and tumor masses were derived from pretherapeutic (68)Ga-PSMA-HBED-CC PET/CT. Absorbed doses for individual cycles were calculated using OLINDA/EXM. SUVs from pretherapeutic PET were compared with absorbed doses and with change of SUV. Results: The mean whole-body effective dose for all cycles was 0.06 ± 0.03 Sv/GBq. The mean absorbed organ doses were 0.72 ± 0.21 Gy/GBq for the kidneys; 0.12 ± 0.06 Gy/GBq for the liver; and 0.55 ± 0.14 Gy/GBq for the parotid, 0.64 ± 0.40 Gy/GBq for the submandibular, and 3.8 ± 1.4 Gy/GBq for the lacrimal glands. Absorbed organ doses were relatively constant among the 4 different cycles. Tumor lesions received a mean absorbed dose per cycle of 3.2 ± 2.6 Gy/GBq (range, 0.22-12 Gy/GBq). Doses to tumor lesions gradually decreased, with 3.5 ± 2.9 Gy/GBq for the first, 3.3 ± 2.5 Gy/GBq for the second, 2.7 ± 2.3 Gy/GBq for the third, and 2.4 ± 2.2 Gy/GBq for the fourth cycle. SUVs of pretherapeutic PET moderately correlated with absorbed dose (r = 0.44, P < 0.001 for SUVmax; r = 0.43, P < 0.001 for SUVmean) and moderately correlated with the change of SUV (r = 0.478, P < 0.001 for SUVmax, and r = 0.50, P < 0

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

    PubMed

    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

  12. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer.

    PubMed

    Ahmadzadehfar, Hojjat; Eppard, Elisabeth; Kürpig, Stefan; Fimmers, Rolf; Yordanova, Anna; Schlenkhoff, Carl Diedrich; Gärtner, Florian; Rogenhofer, Sebastian; Essler, Markus

    2016-03-15

    Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64-82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17-2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients.

  13. Therapeutic response and side effects of repeated radioligand therapy with 177Lu-PSMA-DKFZ-617 of castrate-resistant metastatic prostate cancer

    PubMed Central

    Ahmadzadehfar, Hojjat; Eppard, Elisabeth; Kürpig, Stefan; Fimmers, Rolf; Yordanova, Anna; Schlenkhoff, Carl Diedrich; Gärtner, Florian; Rogenhofer, Sebastian; Essler, Markus

    2016-01-01

    Prostate-specific membrane antigen (PSMA) is highly expressed on prostate epithelial cells and strongly up-regulated in prostate cancer (PC), making it an optimal target for the treatment of metastasized PC. Radioligand therapy (RLT) with 177Lu-PSMA-DKFZ-617 (Lu-PSMA) is a targeted therapy for metastatic PC. In this study, we retrospectively analyzed the side effects and the response rate of 24 hormone and/or chemorefractory PC patients with a mean age of 75.2 years (range: 64–82) with distant metastases and progressive disease according to the PSA level, who were treated with Lu-PSMA. Median PSA was 522 ng/ml (range: 17–2360). Forty-six cycles of Lu-PSMA were performed. Of the 24 patients, 22 received two cycles. Eight weeks after the first cycle of Lu-PSMA therapy 79.1% experienced a decline in PSA level. Eight weeks after the second cycle of Lu-PSMA therapy 68.2% experienced a decline in PSA relative to the baseline value. Apart from two cases of grade 3 anemia, there was no relevant hemato- or nephrotoxicity (grade 3 or 4). These results confirmed that Lu-PSMA is a safe treatment option for metastatic PC patients and has a low toxicity profile. A positive response to therapy in terms of decline in PSA occurs in about 70% of patients. PMID:26871285

  14. First-in-Human Experience of CXCR4-Directed Endoradiotherapy with 177Lu- and 90Y-Labeled Pentixather in Advanced-Stage Multiple Myeloma with Extensive Intra- and Extramedullary Disease.

    PubMed

    Herrmann, Ken; Schottelius, Margret; Lapa, Constantin; Osl, Theresa; Poschenrieder, Andreas; Hänscheid, Heribert; Lückerath, Katharina; Schreder, Martin; Bluemel, Christina; Knott, Markus; Keller, Ulrich; Schirbel, Andreas; Samnick, Samuel; Lassmann, Michael; Kropf, Saskia; Buck, Andreas K; Einsele, Hermann; Wester, Hans-Juergen; Knop, Stefan

    2016-02-01

    Chemokine receptor 4 (CXCR4) is a key factor for tumor growth and metastasis in several types of human cancer. Based on promising experiences with a radiolabeled CXCR4 ligand ((68)Ga-pentixafor) for diagnostic receptor targeting, (177)Lu- and (90)Y-pentixather were recently developed as endoradiotherapeutic vectors. Here, we summarize the first-in-human experience in 3 heavily pretreated patients with intramedullary and extensive extramedullary manifestations of multiple myeloma undergoing CXCR4-directed endoradiotherapy. CXCR4 target expression was demonstrated by baseline (68)Ga-pentixafor PET. Each treatment was approved by the clinical ethics committee. Pretherapeutic (177)Lu-pentixather dosimetry was performed before (177)Lu-pentixather or (90)Y-pentixather treatment. Subsequently, patients underwent additional chemotherapy and autologous stem cell transplantation for bone marrow rescue. A remarkable therapeutic effect was visualized in 2 patients, who showed a significant reduction in (18)F-FDG uptake. CXCR4-targeted radiotherapy with pentixather appears to be a promising novel treatment option in combination with cytotoxic chemotherapy and autologous stem cell transplantation, especially for patients with advanced multiple myeloma. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

  15. The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy.

    PubMed

    Werner, Rudolf A; Beykan, Seval; Higuchi, Takahiro; Lückerath, Katharina; Weich, Alexander; Scheurlen, Michael; Bluemel, Christina; Herrmann, Ken; Buck, Andreas K; Lassmann, Michael; Lapa, Constantin; Hänscheid, Heribert

    2016-07-05

    Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of 99mTc-mercaptoacetyltriglycine (99mTc--MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq 177Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m² before PRRT (baseline) and 221 ± 45 ml/min/1.73 m² after a median follow-up of 370 days. The age-corrected decrease (mean: -3%, range: -27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=-0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by 99mTc-MAG3-clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy.

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

    PubMed

    Ocak, Meltem; Helbok, Anna; von Guggenberg, Elisabeth; Ozsoy, Y; Kabasakal, Levent; Kremser, Leopold; Decristoforo, Clemens

    2011-02-01

    Lack of correlation between in vitro and in vivo stability is a general problem for the development of radiopeptides especially in the case of minigastrin derivatives for therapeutic applications. In this study, we compared the influence of experimental conditions on radiopeptide stability results in vitro using a model Minigastrin (MG) analogue labelled with Lu-177. Additionally, we attempted to characterize the main serum enzymatic cleavage sites by matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) analysis. In vitro stability of a DOTA-minigastrin derivative ((177)Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-NIe-Asp-Phe-NH(2)) was tested in serum, rat tissue homogenates and two different standardised enzymatic mixtures. Quantification of the metabolised radiopeptides at different time intervals was performed using reversed-phase high-performance liquid chromatography (RP-HPLC). Metabolites were characterised by MALDI-TOF-MS. Urine was collected after 15 min p.i. into the mice and compared with in vitro metabolites by RP-HPLC. Faster degradation of the radiopeptide was found in blood in comparison with plasma and serum incubation and in components from rats faster than from human origin. Fast degradation was observed in kidney and liver homogenates as well as in standardised enzymatic mixtures, also revealing variations in the metabolic profile. In urine, no intact peptide was detected already 5 min post injection. MALDI-TOF-MS revealed major cleavage sites at the carboxy terminus of the peptide. Very variable results may be found when different kind of incubation media for testing radiopeptide stabilities is used. Serum incubation studies may overestimate stability; therefore, results should be interpreted with care and combined with alternative in vitro and in vivo investigations. Copyright © 2011 Elsevier Inc. All rights reserved.

  17. The impact of 177Lu-octreotide therapy on 99mTc-MAG3 clearance is not predictive for late nephropathy

    PubMed Central

    Werner, Rudolf A.; Beykan, Seval; Higuchi, Takahiro; Lückerath, Katharina; Weich, Alexander; Scheurlen, Michael; Bluemel, Christina; Herrmann, Ken; Buck, Andreas K.; Lassmann, Michael

    2016-01-01

    Peptide Receptor Radionuclide Therapy (PRRT) for the treatment of neuroendocrine tumors may lead to kidney deterioration. This study aimed to evaluate the suitability of 99mTc-mercaptoacetyltriglycine (99mTc­-MAG3) clearance for the early detection of PRRT-induced changes on tubular extraction (TE). TE rate (TER) was measured prior to 128 PRRT cycles (7.6±0.4 GBq 177Lu-octreotate/octreotide each) in 32 patients. TER reduction during PRRT was corrected for age-related decrease and analyzed for the potential to predict loss of glomerular filtration (GF). The GF rate (GFR) as measure for renal function was derived from serum creatinine. The mean TER was 234 ± 53 ml/min/1.73 m2 before PRRT (baseline) and 221 ± 45 ml/min/1.73 m2 after a median follow-up of 370 days. The age-corrected decrease (mean: −3%, range: −27% to +19%) did not reach significance (p=0.09) but significantly correlated with the baseline TER (Spearman p=−0.62, p<0.001). Patients with low baseline TER showed an improved TER after PRRT, high decreases were only observed in individuals with high baseline TER. Pre-therapeutic TER data were inferior to plasma creatinine-derived GFR estimates in predicting late nephropathy. TER assessed by 99mTc-MAG3­clearance prior to and during PRRT is not suitable as early predictor of renal injury and an increased risk for late nephropathy. PMID:27259246

  18. Novel series of (177)Lu-labeled bombesin derivatives with amino acidic spacers for selective targeting of human PC-3 prostate tumor cells.

    PubMed

    Pujatti, P B; Santos, J S; Couto, R M; Melero, L T U H; Suzuki, M F; Soares, C R J; Grallert, S R M; Mengatti, J; De Araújo, E B

    2011-06-01

    Bombesin (BBN) has demonstrated the ability to bind with high affinity and specificity to GRP receptor, overexpressed on human prostate cancer. A large number of BBN derivatives have been synthesized for this purpose but most of them exhibit high abdominal accumulation, which may represent a problem in their clinical use due to serious side effects to patients. In this study we describe the results of radiolabeling with lutetium-177, stability and in vivo studies of novel phenyl-glycine-extended bombesin derivatives. The spacers were inserted to improve bombesin in vivo properties and to reduce its target to non-tumor sites. Preliminary studies were done to establish the ideal conditions for labeling bombesin derivatives. Chromatography systems were applied to determine free lutetium and the stability of the preparations was evaluated either after storing at 2-8 ºC or incubation in human serum at 37 ºC. In vivo experiments included biodistribution, pharmacokinetics and SPECT images and were performed in Balb-c and Nude mice bearing PC-3 xenografts. The derivatives were labeled with high yield and kept stable at 2-8 ºC and are metabolized by human serum enzymes. In vivo studies showed fast blood clearance of labeled peptides and rapid excretion, performed mainly by renal pathway. In addition, biodistribution and imaging studies showed low abdominal accumulation and significant and specific tumor uptake of (177)Lu-labeled derivatives. The derivative with longer spacer holds a higher potential as radiopharmaceutical for prostate tumor diagnosis and the derivatives with shorter spacers are potential radiopharmaceuticals for prostate tumor treatment.

  19. 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.

    PubMed

    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 < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of (177)Lu-HA in the joints. All patients showed decreased joint swelling and pains, resulting in increased joint motion after 6 months. The percentage of VAS improvement from baseline values was 79.5 ± 20.0% 6 months after RS and found to be significantly related to patients' age (P = 0.01) and duration of the disease (P = 0.03). Knees with Steinbrocker's Grades 0 and I responded better than those

  20. 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

    PubMed Central

    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 177Lu-labeled hydroxyapatite (177Lu-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 177Lu-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 < 25), fair (VAS ≥ 25-50), good (VAS ≥ 50-75) and excellent (VAS ≥ 75), with excellent and good results considered to be success, while fair and poor as failure and also by range of motion. Three phase bone scan (BS) was repeated after 6 months and changes in the second phase of BS3 were assessed visually, using a four-degree scale and in the third phase, semiquantitatively with J/B ratio to see the response. Biochemical analysis of C-reactive protein (CRP) and fibrinogen was repeated after 48 h, 4 and 24 weeks. In all 10 patients, no leakage of administered activity to nontarget organs was visible in the whole-body scan. Static scans of the joint at 1 month revealed complete retention of 177Lu-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

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

    PubMed

    Kabasakal, Levent; AbuQbeitah, Mohammad; Aygün, Aslan; Yeyin, Nami; Ocak, Meltem; Demirci, Emre; Toklu, Turkay

    2015-12-01

    (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 (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 (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 (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

  2. In vitro and in vivo evaluation of melanin-binding decapeptide 4B4 radiolabeled with 177Lu, 166Ho, and 153Sm radiolanthanides for the purpose of targeted radionuclide therapy of melanoma.

    PubMed

    Ballard, Beau; Jiang, Zewei; Soll, Clifford E; Revskaya, Ekaterina; Cutler, Cathy S; Dadachova, Ekaterina; Francesconi, Lynn C

    2011-10-01

    Melanoma is a malignancy with increasing incidence. Although primary tumors that are localized to the skin can be successfully treated by surgical removal, there is no satisfactory treatment for metastatic melanoma, a condition that has currently an estimated 5-year survival of just 6%. During the last decade, β- or α-emitter-radiolabeled peptides that bind to different receptors on a variety of tumors have been investigated as potential therapeutic agents in both the preclinical and clinical settings with encouraging results. A recent study demonstrated that 188-Rhenium ((188)Re)-labeled, via HYNIC ligand, fungal melanin-binding decapeptide 4B4 was effective against experimental MNT1 human melanoma and was safe to normal melanized tissues. The availability of radiolanthanides with diverse nuclear emission schemes and half-lives provides an opportunity to expand the repertoire of peptides for radionuclide therapy of melanoma. The melanin-binding decapeptide 4B4 was radiolabeled with (177)Lu, (166)Ho, and (153)Sm via a DO3A chelate. The stability studies of Ln*-DO3A-4B4 in phosphate-buffered saline, serum, and a hydroxyapatite assay demonstrated that (177)Lu-labeled peptide was more stable than (166)Ho- and (153)Sm-labeled peptides, most likely because of the smallest ionic radius of the former allowing for better complexation with DO3A. Binding of Ln*-DO3A-4B4 to the lysed highly melanized MNT1 melanoma cells demonstrated the specificity of peptides binding to melanin. In vivo biodistribution data for (177)Lu-DO3A-4B4 given by intraperitoneal administration to lightly pigmented human metastatic A2058 melanoma-bearing mice demonstrated very high uptake in the kidneys and low tumor uptake. Intravenous administration did not improve the tumor uptake. The plausible explanation of low tumor uptake of (177)Lu-DO3A-4B4 could be its decreased ability to bind to melanin during in vitro binding studies in comparison with (188)Re-HYNIC-4B4, exacerbated by the very fast

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

    PubMed

    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

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

    PubMed Central

    Basu, Sandip; Ranade, Rohit; Thapa, Pradeep

    2016-01-01

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

  5. Sequential determination of Pu and Am radioisotopes in environmental samples; a comparison of two separation procedures.

    PubMed

    Jakopic, Rozle; Tavcar, Polona; Benedik, Ljudmila

    2007-05-01

    Two separation methods for the sequential determination of Am and Pu radionuclides are presented and the results obtained are compared. Analysis involves leaching the sample with concentrated nitric acid (HNO(3)), followed by radiochemical separation using extraction chromatographic resins (UTEVA, TRU) and anion exchange. Sources for alpha spectrometry were prepared by micro-precipitation on neodymium fluoride (NdF(3)). The chemical recoveries were determined using (242)Pu and (243)Am tracers. The methods were tested on reference materials and on two sediments. All the results were in good agreement with the reference values. The evaluation of uncertainty is also included.

  6. Biological evaluation of (177)Lu-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.

    PubMed

    Lim, Jae Cheong; Cho, Eun Ha; Kim, Jin Joo; Choi, Sang Mu; Lee, So young; Nam, Sung Soo; Park, Ul Jae; Park, Soo Hyun

    2015-02-01

    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(SO3H)-Aminooctanoyl-Gln-Trp-Ala-Val-N methyl Gly-His-Statine-Leu-NH2 (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 4hr. 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 1.5hr p.i., and was increased to 216.33±61.58 at 24hr 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. Copyright © 2014 Elsevier Inc. All rights reserved.

  7. Separation of Transmutation - and Fission-Produced Radioisotopes from Irradiated Beryllium

    SciTech Connect

    Troy J. Tranter; RIchard D. Tillotson; Nick R. Mann; Glen R. Longhurst

    2011-11-01

    The primary objective of this study was to test the effectiveness of a two-step solvent extraction-precipitation process for separating transmutation and fission products from irradiated beryllium. Beryllium metal was dissolved in nitric and fluoroboric acids. Isotopes of 241Am, 239Pu, 85Sr, 60Co, and 137Cs were then added to make a surrogate beryllium waste solution. A series of batch contacts was performed with the spiked simulant using chlorinated cobalt dicarbollide and polyethylene glycol diluted with sulfone to extract the isotopes of Cs and Sr. Another series of batch contacts was performed using a combination of octyl (phenyl)-N,Ndiisobutylcarbamoylmethylphosphine oxide in tributyl phosphate diluted with dodecane for extracting the isotopes of Pu and Am. The 60Co was separated by first forming a cobalt complex and then selectively precipitating the beryllium as a hydroxide. The results indicate that greater than 99.9% removal can be achieved for each radionuclide. Transuranic isotope contamination levels are reduced to less than 100 nCi/g, and sources of high beta-gamma radiation (60Co, 137Cs, and 90Sr) are reduced to levels that will allow the beryllium to be contact handled. The separation process may be applicable to a recycle or waste disposition scenario.

  8. Field task proposal/agreement separation and purification of radioisotopes for research

    SciTech Connect

    Wilkes, W.R.; Eppley, R.E.

    1980-11-20

    The present purpose of this program is to produce high-purity uranium-234 (99%) and polonium-209 for the scientific community, both Governmental and non-Governmental. In addition, facilities for separation and purification of protactinium-231, thorium-230, and thorium-229 are maintained in stand-by condition for the resumption of these processes when conditions warrant. The uranium-234 isotope is separated from aged plutonium-238 material, purified, and converted to solid U{sub 3}O{sub 8}. This oxide is subsequently shipped to Oak Ridge National Laboratory for distribution through their Isotope Sales Group. The principal use of uranium-234, which is recovered from aged plutonium-238, is in fission detectors used to monitor reactors. Approximately one-third of the total uranium in a fission detector is uranium-234. The other two-thirds is uranium-235. A typical detector might contain 15 mg total uranium. As the neutron flux in the reactor causes fission of the uranium-235 in the detector, it also converts the uranium-234 to uranium-235.

  9. A Monte Carlo approach to small-scale dosimetry of solid tumour microvasculature for nuclear medicine therapies with (223)Ra-, (131)I-, (177)Lu- and (111)In-labelled radiopharmaceuticals.

    PubMed

    Amato, Ernesto; Leotta, Salvatore; Italiano, Antonio; Baldari, Sergio

    2015-07-01

    The small-scale dosimetry of radionuclides in solid-tumours is directly related to the intra-tumoral distribution of the administered radiopharmaceutical, which is affected by its egress from the vasculature and dispersion within the tumour. The aim of the present study was to evaluate the combined dosimetric effects of radiopharmaceutical distribution and range of the emitted radiation in a model of tumour microvasculature. We developed a computational model of solid-tumour microenvironment around a blood capillary vessel, and we simulated the transport of radiation emitted by (223)Ra, (111)In, (131)I and (177)Lu using the GEANT4 Monte Carlo. For each nuclide, several models of radiopharmaceutical dispersion throughout the capillary vessel were considered. Radial dose profiles around the capillary vessel, the Initial Radioactivity (IR) necessary to deposit 100 Gy of dose at the edge of the viable tumour-cell region, the Endothelial Cell Mean Dose (ECMD) and the Tumour Edge Mean Dose (TEMD), i.e. the mean dose imparted at the 250-μm layer of tissue, were computed. The results for beta and Auger emitters demonstrate that the photon dose is about three to four orders of magnitude lower than that deposited by electrons. For (223)Ra, the beta emissions of its progeny deliver a dose about three orders of magnitude lower than that delivered by the alpha emissions. Such results may help to characterize the dose inhomogeneities in solid tumour therapies with radiopharmaceuticals, taking into account the interplay between drug distribution from vasculature and range of ionizing radiations.

  10. Interface of a particle collector with on-line electrochemically-modulated separation system for analysis of airborne radioisotopes

    SciTech Connect

    Duckworth, Douglas {Doug} C

    2005-01-01

    The International Monitoring System is part of the global verification system of the Comprehensive Nuclear-Test-Ban Treaty and comprises an atmospheric radioactivity monitoring network of 80 particulate stations, 40 of which are to be equipped with noble-gas-detection capability. The network is supported by 16 radionuclide laboratories. The equipment has to be tailored to different environments and its reliability is proving to be an operational challenge. A novel device for collecting, concentrating and separating airborne particles in situ is under development through a collaborative effort between Savannah River Technology Center (SRTC) and Oak Ridge National Laboratory (ORNL). This work entails coupling an Aerosol-to-Liquid Particle Extraction System (ALPES) to an electrochemically modulated separation (EMS) cell. The ALPES collects and concentrates airborne particles into a liquid, and the EMS cell separates species based on their affinity for a charged target surface. Preliminary data indicates substantial sensitivity enhancement may be realized by interfacing these devices. The system will allow for rapid field analysis of radionuclides while providing reductions in labor, cost, and turnaround time compared to standard radiometric techniques.

  11. Radioisotope trithiol complexes

    DOEpatents

    Jurisson, Silvia S.; Cutler, Cathy S.; Degraffenreid, Anthony J.

    2016-08-30

    The present invention is directed to a series of stable radioisotope trithiol complexes that provide a simplified route for the direct complexation of radioisotopes present in low concentrations. In certain embodiments, the complex contains a linking domain configured to conjugate the radioisotope trithiol complex to a targeting vector. The invention is also directed to a novel method of linking the radioisotope to a trithiol compound to form the radioisotope trithiol complex. The inventive radioisotope trithiol complexes may be utilized for a variety of applications, including diagnostics and/or treatment in nuclear medicine.

  12. 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.

    PubMed

    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.

  13. Radioisotopes: Today's Applications.

    ERIC Educational Resources Information Center

    Department of Energy, Washington, DC. Nuclear Energy Office.

    Radioisotopes are useful because of their three unique characteristics: (1) radiation emission; (2) predictable radioactive lives; and (3) the same chemical properties as the nonradioactive atoms of that element. Researchers are able to "order" a radioisotope with the right radiation, half-life, and chemical property to perform a given task with…

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

    SciTech Connect

    Larsson, Erik; Ljungberg, Michael; Martensson, Linda; Nilsson, Rune; Tennvall, Jan; Strand, Sven-Erik; Joensson, Bo-Anders

    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

  15. Radioisotopic heat source

    DOEpatents

    Sayell, E.H.

    1973-10-23

    A radioisotopic heat source is described which includes a core of heat productive, radioisotopic material, an impact resistant layer of graphite surrounding said core, and a shell of iridium metal intermediate the core and the impact layer. The source may also include a compliant mat of iridium between the core and the iridium shell, as well as an outer covering of iridium metal about the entire heat source. (Official Gazette)

  16. Radioisotope Production for Medical and Physics Applications

    NASA Astrophysics Data System (ADS)

    Mausner, Leonard

    2012-10-01

    Radioisotopes are critical to the science and technology base of the US. Discoveries and applications made as a result of the availability of radioisotopes span widely from medicine, biology, physics, chemistry and homeland security. The clinical use of radioisotopes for medical diagnosis is the largest sector of use, with about 16 million procedures a year in the US. The use of ^99Mo/^99mTc generator and ^18F make up the majority, but ^201Tl, ^123I, ^111In, and ^67Ga are also used routinely to perform imaging of organ function. Application of radioisotopes for therapy is dominated by use of ^131I for thyroid malignancies, ^90Y for some solid tumors, and ^89Sr for bone cancer, but production of several more exotic species such as ^225Ac and ^211At are of significant current research interest. In physics ^225Ra is of interest for CP violation studies, and the actinides ^242Am, ^249Bk, and ^254Es are needed as targets for experiments to create superheavy elements. Large amounts of ^252Cf are needed as a fission source for the CARIBU experiment at ANL. The process of radioisotope production is multidisciplinary. Nuclear physics input based on nuclear reaction excitation function data is needed to choose an optimum target/projectile in order to maximize desired isotope production and minimize unwanted byproducts. Mechanical engineering is needed to address issues of target heating, induced mechanical stress and material compatibility of target and claddings. Radiochemists are involved as well since chemical separation to purify the desired final radioisotope product from the bulk target and impurities is also usually necessary. Most neutron rich species are produced at a few government and university reactors. Other radioisotopes are produced in cyclotrons in the commercial sector, university/hospital based facilities, and larger devices at the DOE labs. The landscape of US facilities, the techniques involved, and current supply challenges will be reviewed.

  17. Modular Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

    2016-01-01

    High-efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRGs) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high-specific-power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTGs). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and the Department of Energy (DOE) called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered, which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provided about 50 to 450 W of direct current (DC) to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator, which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific

  18. Cyclotron Production of Medical Radioisotopes

    SciTech Connect

    Avila-Rodriguez, M. A.; Zarate-Morales, A.; Flores-Moreno, A.

    2010-08-04

    The cyclotron production of radioisotopes for medical applications is gaining increased significance in diagnostic molecular imaging techniques such as PET and SPECT. In this regard, radioisotope production has never been easier or more convenient until de introduction of compact medical cyclotrons in the last few decades, which allowed the use of short-lived radioisotopes in in vivo nuclear medicine studies on a routine basis. This review outlines some general considerations about the production of radioisotopes using charged particle accelerators.

  19. Radioisotopic heat source

    DOEpatents

    Jones, G.J.; Selle, J.E.; Teaney, P.E.

    1975-09-30

    Disclosed is a radioisotopic heat source and method for a long life electrical generator. The source includes plutonium dioxide shards and yttrium or hafnium in a container of tantalum-tungsten-hafnium alloy, all being in a nickel alloy outer container, and subjected to heat treatment of from about 1570$sup 0$F to about 1720$sup 0$F for about one h. (auth)

  20. Miniature Radioisotope Power Source

    NASA Technical Reports Server (NTRS)

    Chmielewski, Artur B.

    1995-01-01

    Proposed miniature power source generates electricity for years from heat developed in small radioisotope unit without addition of fuel or dependence on sunlight. Called powerstick, is relatively inexpensive, lightweight, and rugged. Supplies power to small vehicles or scientific instruments in remote locations on Earth or in outer space. Envisioned uses include Mars miniature rovers and monitoring equipment for toxic or nuclear storage sites.

  1. Modular Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.; Mason, Lee S.; Schifer, Nicholas A.

    2015-01-01

    High efficiency radioisotope power generators will play an important role in future NASA space exploration missions. Stirling Radioisotope Generators (SRG) have been identified as a candidate generator technology capable of providing mission designers with an efficient, high specific power electrical generator. SRGs high conversion efficiency has the potential to extend the limited Pu-238 supply when compared with current Radioisotope Thermoelectric Generators (RTG). Due to budgetary constraints, the Advanced Stirling Radioisotope Generator (ASRG) was canceled in the fall of 2013. Over the past year a joint study by NASA and DOE called the Nuclear Power Assessment Study (NPAS) recommended that Stirling technologies continue to be explored. During the mission studies of the NPAS, spare SRGs were sometimes required to meet mission power system reliability requirements. This led to an additional mass penalty and increased isotope consumption levied on certain SRG-based missions. In an attempt to remove the spare power system, a new generator architecture is considered which could increase the reliability of a Stirling generator and provide a more fault-tolerant power system. This new generator called the Modular Stirling Radioisotope Generator (MSRG) employs multiple parallel Stirling convertor/controller strings, all of which share the heat from the General Purpose Heat Source (GPHS) modules. For this design, generators utilizing one to eight GPHS modules were analyzed, which provide about 50 to 450 watts DC to the spacecraft, respectively. Four Stirling convertors are arranged around each GPHS module resulting in from 4 to 32 Stirling/controller strings. The convertors are balanced either individually or in pairs, and are radiatively coupled to the GPHS modules. Heat is rejected through the housing/radiator which is similar in construction to the ASRG. Mass and power analysis for these systems indicate that specific power may be slightly lower than the ASRG and

  2. Chemistry and bifunctional chelating agents for binding (177)Lu.

    PubMed

    Parus, Józef L; Pawlak, Dariusz; Mikolajczak, Renata; Duatti, Adriano

    2015-01-01

    A short overview of fundamental chemistry of lutetium and of structural characteristics of lutetium coordination complexes, as relevant for understanding the properties of lutetium-177 radiopharmaceuticals, is presented. This includes basic concepts on lutetium electronic structure, lanthanide contraction, coordination geometries, behavior in aqueous solution and thermodynamic stability. An illustration of the structure and binding properties of the most important chelating agents for the Lu(3+) ion in aqueous solution is also reported with specific focus on coordination complexes formed with linear and macrocyclic polydentate amino-carboxylate donor ligands.

  3. Safe use of radioisotopes.

    PubMed

    Meisenhelder, Jill; Semba, Kentaro

    2006-09-01

    The use of radioisotopes to label specific molecules in a defined way has greatly furthered the discovery and dissection of biochemical pathways. The development of methods to synthesize such tagged biological compounds inexpensively on an industrial scale has enabled them to be used routinely in laboratory protocols, including many detailed in this manual. Although most of these protocols involve the use of only microcurie amounts of radioactivity, some (particularly those describing the metabolic labeling of proteins or nucleic acids within cells) require amounts on the order of millicuries. In all cases where radioisotopes are used, depending on the quantity and nature of the isotope, certain precautions must be taken to ensure the safety of the scientist. It is essential to use good safety practices and proper protection to handle radioactive substances. This unit discusses handling, storage, and disposal of the isotopes most frequently used in biological research.

  4. Safe use of radioisotopes.

    PubMed

    Meisenhelder, Jill; Semba, Kentaro

    2006-06-01

    The use of radioisotopes to label specific molecules in a defined way has greatly furthered the discovery and dissection of biochemical pathways. The development of methods to synthesize such tagged biological compounds inexpensively on an industrial scale has enabled them to be used routinely in laboratory protocols, including many detailed in this manual. Although most of these protocols involve the use of only microcurie amounts of radioactivity, some (particularly those describing the metabolic labeling of proteins or nucleic acids within cells) require amounts on the order of millicuries. In all cases where radioisotopes are used, depending on the quantity and nature of the isotope, certain precautions must be taken to ensure the safety of the scientist. It is essential to use good safety practices and proper protection to handle radioactive substances. This unit discusses handling, storage, and disposal of the isotopes most frequently used in biological research.

  5. Taming Highly Charged Radioisotopes

    NASA Astrophysics Data System (ADS)

    Chowdhury, Usman; Eberhardt, Benjamin; Jang, Fuluni; Schultz, Brad; Simon, Vanessa; Delheij, Paul; Dilling, Jens; Gwinner, Gerald

    2012-10-01

    The precise and accurate mass of short-lived radioisotopes is a very important parameter in physics. Contribution to the improvement of nuclear models, metrological standard fixing and tests of the unitarity of the Caibbibo-Kobayashi-Maskawa (CKM) matrix are a few examples where the mass value plays a major role. TRIUMF's ion trap for atomic and nuclear physics (TITAN) is a unique facility of three online ion traps that enables the mass measurement of short-lived isotopes with high precision (˜10-8). At present TITAN's electron beam ion trap (EBIT) increases the charge state to increase the precision, but there is no facility to significantly reduce the energy spread introduced by the charge breeding process. The precision of the measured mass of radioisotopes is linearly dependent on the charge state while the energy spread of the charged radioisotopes affects the precision adversely. To boost the precision level of mass measurement at TITAN without loosing too many ions, a cooler Penning trap (CPET) is being developed. CPET is designed to use either positively (proton) or negatively (electron) charged particles to reduce the energy spread via sympathetic cooling. Off-line setup of CPET is complete. Details of the working principles and updates are presented

  6. Radioisotope study of salivary glands

    SciTech Connect

    De Rossi, G.

    1987-01-01

    The book discusses the use of radioisotope methods in the diagnosis of salivary gland diseases. Anatomical and physiological features of the salivary gland are summarized and radiotracer deposition processes are described. Clinical applications of scintigraphy are detailed. The degree of functional impairment due to various inflammatory diseases is contrasted by means of semiquantitative computerized methods with follow-up therapeutic results. Post-irradiatory involvement and possible functional recovery of salivary glands are also considered. The contents discussed are: Salivary Gland Physiology and Radioisotope Uptake. Radioisotope Study of Salivary Glands. Radioisotope Studies Under Normal Conditions. Survey of Radiographic Methods. Dosimetric Assessment. Conclusions and Index.

  7. Radioisotope Power System Pool Concept

    NASA Technical Reports Server (NTRS)

    Rusick, Jeffrey J.; Bolotin, Gary S.

    2015-01-01

    Advanced Radioisotope Power Systems (RPS) for NASA deep space science missions have historically used static thermoelectric-based designs because they are highly reliable, and their radioisotope heat sources can be passively cooled throughout the mission life cycle. Recently, a significant effort to develop a dynamic RPS, the Advanced Stirling Radioisotope Generator (ASRG), was conducted by NASA and the Department of Energy, because Stirling based designs offer energy conversion efficiencies four times higher than heritage thermoelectric designs; and the efficiency would proportionately reduce the amount of radioisotope fuel needed for the same power output. However, the long term reliability of a Stirling based design is a concern compared to thermoelectric designs, because for certain Stirling system architectures the radioisotope heat sources must be actively cooled via the dynamic operation of Stirling converters throughout the mission life cycle. To address this reliability concern, a new dynamic Stirling cycle RPS architecture is proposed called the RPS Pool Concept.

  8. Safe use of radioisotopes.

    PubMed

    Meisenhelder, Jill; Bursik, Steve

    2010-04-01

    The pursuit of scientific knowledge has been considerably advanced by the use of biochemical molecules that incorporate radioisotopes at specific sites. The fate of these labeled molecules, and/or the radiolabeled products that result from biochemical reactions in which the parent molecule was involved, can be traced using a variety of instruments that detect radioactivity. This appendix begins with a discussion of the principles of radioactivity in order to provide the reader/user with knowledge on which to base a common sense approach to the safe use of isotopes. The characteristics of isotopes most commonly used in a molecular biology laboratory are then detailed, as well as the safety precautions and monitoring methods peculiar to each one. Detection and imaging methods used in experimental analysis are reviewed. Finally, an outline of an orderly response to a spill of radioactive material is presented.

  9. Safe use of radioisotopes.

    PubMed

    Meisenhelder, Jill; Bursik, Steve

    2007-07-01

    The pursuit of scientific knowledge has been considerably advanced by the use of biochemical molecules that incorporate radioisotopes at specific sites. The fate of these labeled molecules, and/or the radiolabeled products that result from biochemical reactions in which the parent molecule was involved, can be traced using a variety of instruments that detect radioactivity. This appendix begins with a discussion of the principles of radioactivity in order to provide the reader/user with knowledge on which to base a common sense approach to the safe use of isotopes. The characteristics of isotopes most commonly used in a molecular biology laboratory are then detailed, as well as the safety precautions and monitoring methods peculiar to each one. Detection and imaging methods used in experimental analysis are reviewed. Finally, an outline of an orderly response to a spill of radioactive material is presented.

  10. Safe use of radioisotopes.

    PubMed

    Meisenhelder, Jill; Bursik, Steve

    2008-08-01

    The pursuit of scientific knowledge has been considerably advanced by the use of biochemical molecules that incorporate radioisotopes at specific sites. The fate of these labeled molecules, and/or the radiolabeled products that result from biochemical reactions in which the parent molecule was involved, can be traced using a variety of instruments that detect radioactivity. This appendix begins with a discussion of the principles of radioactivity in order to provide the reader/user with knowledge on which to base a common sense approach to the safe use of isotopes. The characteristics of isotopes most commonly used in a molecular biology laboratory are then detailed, as well as the safety precautions and monitoring methods peculiar to each one. Detection and imaging methods used in experimental analysis are reviewed. Finally, an outline of an orderly response to a spill of radioactive material is presented.

  11. Radioisotope Space Power Programs

    NASA Technical Reports Server (NTRS)

    Rock, B. J.

    1984-01-01

    Radioisotope Thermoelectric Generators (RTGs) were extensively used in past space missions with great success. An improved generation of RTGs employing a new lightweight, modular heat source is being built by the DOE for NASA launches in 1986. More advanced modular RTGs which promise power-to-weight ratios of over 8.8 watts(e)/kg (4 watts(e)/lb) are currently under development by the DOE and could be flight-ready within five years. Dynamic Isotope Power Systems (DIPS) which offer 18-20% conversion efficiencies were demonstrated by the DOE in ground tests. DIPS would be useful for several military missions requiring power in the low-kilowatt range. These systems could also be brought to flight readiness by the DOE following receipt of firm user requirements.

  12. Accelerated Decay of Radioisotopes

    DTIC Science & Technology

    2013-01-01

    00-01 -2013 Technical June20 l l-June 2012 4 . TITLE AND SUBTITLE Sa. CONTRACT NUMBER DTRA MIPR 11-2362M Accelerated Decay of Radioisotopes Sb...268 x E +2 4.788 026 x E -2 6.894 757 4.535 924 x E -1 4.214 011 x E -2 1.601 846 x E +1 1.000 000 x E -2 2.579 760 x E - 4 1.000 000 x E -8...c a y o f R a d i o i s o t o p e s " P r o p o s a l # B R C A L L 0 7 - N - 2 - 0 0 4 7 I l l u s t r a t i o n o f \\ P F R P a s p o

  13. Silicon Carbide Radioisotope Batteries

    NASA Technical Reports Server (NTRS)

    Rybicki, George C.

    2005-01-01

    The substantial radiation resistance and large bandgap of SiC semiconductor materials makes them an attractive candidate for application in a high efficiency, long life radioisotope battery. To evaluate their potential in this application, simulated batteries were constructed using SiC diodes and the alpha particle emitter Americium Am-241 or the beta particle emitter Promethium Pm-147. The Am-241 based battery showed high initial power output and an initial conversion efficiency of approximately 16%, but the power output decayed 52% in 500 hours due to radiation damage. In contrast the Pm-147 based battery showed a similar power output level and an initial conversion efficiency of approximately 0.6%, but no degradation was observed in 500 hours. However, the Pm-147 battery required approximately 1000 times the particle fluence as the Am-242 battery to achieve a similar power output. The advantages and disadvantages of each type of battery and suggestions for future improvements will be discussed.

  14. Production of medical radioisotopes with linear accelerators.

    PubMed

    Starovoitova, Valeriia N; Tchelidze, Lali; Wells, Douglas P

    2014-02-01

    In this study, we discuss producing radioisotopes using linear electron accelerators and address production and separation issues of photoneutron (γ,n) and photoproton (γ,p) reactions. While (γ,n) reactions typically result in greater yields, separating product nuclides from the target is challenging since the chemical properties of both are the same. Yields of (γ,p) reactions are typically lower than (γ,n) ones, however they have the advantage that target and product nuclides belong to different chemical species so their separation is often not such an intricate problem. In this paper we consider two examples, (100)Mo(γ,n)(99)Mo and (68)Zn(γ,p)(67)Cu, of photonuclear reactions. Monte-Carlo simulations of the yields are benchmarked with experimental data obtained at the Idaho Accelerator Center using a 44MeV linear electron accelerator. We propose using a kinematic recoil method for photoneutron production. This technique requires (100)Mo target material to be in the form of nanoparticles coated with a catcher material. During irradiation, (99)Mo atoms recoil and get trapped in the coating layer. After irradiation, the coating is dissolved and (99)Mo is collected. At the same time, (100)Mo nanoparticles can be reused. For the photoproduction method, (67)Cu can be separated from the target nuclides, (68)Zn, using standard exchange chromatography methods. Monte-Carlo simulations were performed and the (99)Mo activity was predicted to be about 7MBq/(g(⁎)kW(⁎)h) while (67)Cu activity was predicted to be about 1MBq/(g(⁎)kW(⁎)h). Experimental data confirm the predicted activity for both cases which proves that photonuclear reactions can be used to produce radioisotopes. Lists of medical isotopes which might be obtained using photonuclear reactions have been compiled and are included as well.

  15. How to Handle Radioisotopes Safely.

    ERIC Educational Resources Information Center

    Sulcoski, John W.

    This booklet is one in a series of instructional aids designed for use by elementary and secondary school science teachers. The various units and forms of radioactive materials used by teachers are first considered. Then, the quantities of radioisotopes that a person may possess without a license from the Atomic Energy Commission (AEC) are…

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

    PubMed

    Das, Tapas; Banerjee, Sharmila

    2016-01-01

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

  17. HFIR-produced medical radioisotopes

    SciTech Connect

    Mirzadeh, S.; Knapp, F.F. Jr.; Beets, A.L.; Alexander, C.W.

    1997-12-01

    We have experimentally determined the yields of a number of medical radioisotopes produced in the Oak Ridge National Laboratory High Flux Isotope Reactor (HFIR) Hydraulic Tube (HT) facility. The HT facility is located in the very high flux region in the flux trap of the reactor, providing on-line access capability while the reactor is operating. The HT facility consists of nine vertically stacked capsules centered just adjacent to the core horizontal midplane. HFIR operates at a nominal power level of 85 MW. The capabilities of the HFIR-HT facilities offer increased efficiency, greater availability, and optimization of radioisotope production, and, as a result, the conservation of rare or expensive target isotopes.

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

    PubMed

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

    2016-07-01

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

  19. Radioisotope production and its utilization in Malaysia

    SciTech Connect

    Yusof, A.b.A.

    1985-01-01

    The PUSPATI TRIGA MARK II research reactor in Malaysia was commissioned in 1982 and production of radioisotope commenced 2 years later. However, radioisotopes have been utilized in the country since 1960 with medical applications pioneering the field, and later followed by usage in industry and agricultural research. Currently, Malaysia spends more than M$1.5 million (US$0.65 million) annually on the import of radioisotopes and associated products. This paper briefly describes the present status of radioisotope utilization in Malaysia. Radioisotopes are being used in the fields of medicine, industry (NDT and quality control, nuclear gauging, radiotracer), agriculture (animal production, food irradiation, soil-plant relationship and mutation breeding studies) and also in environmental control and basic science research. The paper also gives an account of radioisotope production in Malaysia, its facilities and target handling technique.

  20. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1985

    SciTech Connect

    Baker, D.A.

    1986-08-01

    This document describes radioisotope distribution from DOE facilities to private firms including foreign and other DOE facilities. The information is divided into five sections: (1) isotope suppliers, facility contacts, and isotopes or services supplied; (2) customers, suppliers, and isotopes purchased; (3) isotopes purchased cross-referenced with customer numbers; (4) geographic locations of radioisotope customers; and (5) radioisotope sales and transfer - FY 1985.

  1. Cosmogenic radioisotopes on LDEF surfaces

    NASA Technical Reports Server (NTRS)

    Gregory, J. C.; Albrecht, A.; Herzog, G.; Klein, J.; Middleton, R.

    1992-01-01

    The radioisotope Be-7 was discovered in early 1990 on the front surface, and the front surface only, of the LDEF. A working hypothesis is that the isotope, which is known to be mainly produced in the stratosphere by spallation of nitrogen and oxygen nuclei with cosmic ray protons or secondary neutrons, diffuses upward and is absorbed onto metal surfaces of spacecraft. The upward transport must be rapid, that is, its characteristic time scale is similar to, or shorter than, the 53 day half-life of the isotope. It is probably by analogy with meteoritic metal atmospheric chemistry, that the form of the Be at a few 100 km altitude is as the positive ion Be(+) which is efficiently incorporated into the ionic lattice of oxides, such as Al2O3, Cr2O3, Fe2O3, etc., naturally occurring on surfaces of Al and stainless steel. Other radioisotopes of Be, Cl, and C are also produced in the atmosphere, and a search was begun to discover these. Of interest are Be-10 and C-14 for which the production cross sections are well known. The method of analysis is accelerator mass spectrometry. Samples from LDEF clamp plates are being chemically extracted, purified, and prepared for an accelerator run.

  2. Radioisotope penogram in diagnosis of vasculogenic impotence

    SciTech Connect

    Fanous, H.N.; Jevtich, M.J.; Chen, D.C.; Edson, M.

    1982-11-01

    A radioisotope technique to estimate penile blood flow is described. The radioisotope penogram is noninvasive and gives a dynamic evaluation of the arterial supply, venous drainage, and blood flow in the corporeal bodies. The penogram is a valuable adjunct in evaluation of patients with vasculogenic impotence.

  3. Power from Radioisotopes, Understanding the Atom Series.

    ERIC Educational Resources Information Center

    Corliss, William R.; Mead, Robert L.

    This 1971 revision deals with radioisotopes and their use in power generators. Early developments and applications for the Systems for Nuclear Auxiliary Power (SNAP) and Radioisotope Thermoelectric Generators (RTGs) are reviewed. Present uses in space and on earth are included. Uses in space are as power sources in various satellites and space…

  4. Process for radioisotope recovery and system for implementing same

    DOEpatents

    Meikrantz, David H.; Todd, Terry A.; Tranter, Troy J.; Horwitz, E. Philip

    2007-01-02

    A method of recovering daughter isotopes from a radioisotope mixture. The method comprises providing a radioisotope mixture solution comprising at least one parent isotope. The at least one parent isotope is extracted into an organic phase, which comprises an extractant and a solvent. The organic phase is substantially continuously contacted with an aqueous phase to extract at least one daughter isotope into the aqueous phase. The aqueous phase is separated from the organic phase, such as by using an annular centrifugal contactor. The at least one daughter isotope is purified from the aqueous phase, such as by ion exchange chromatography or extraction chromatography. The at least one daughter isotope may include actinium-225, radium-225, bismuth-213, or mixtures thereof. A liquid-liquid extraction system for recovering at least one daughter isotope from a source material is also disclosed.

  5. Process for radioisotope recovery and system for implementing same

    DOEpatents

    Meikrantz, David H [Idaho Falls, ID; Todd, Terry A [Aberdeen, ID; Tranter, Troy J [Idaho Falls, ID; Horwitz, E Philip [Naperville, IL

    2009-10-06

    A method of recovering daughter isotopes from a radioisotope mixture. The method comprises providing a radioisotope mixture solution comprising at least one parent isotope. The at least one parent isotope is extracted into an organic phase, which comprises an extractant and a solvent. The organic phase is substantially continuously contacted with an aqueous phase to extract at least one daughter isotope into the aqueous phase. The aqueous phase is separated from the organic phase, such as by using an annular centrifugal contactor. The at least one daughter isotope is purified from the aqueous phase, such as by ion exchange chromatography or extraction chromatography. The at least one daughter isotope may include actinium-225, radium-225, bismuth-213, or mixtures thereof. A liquid-liquid extraction system for recovering at least one daughter isotope from a source material is also disclosed.

  6. Implanted artificial heart with radioisotope power source.

    PubMed

    Shumakov, V I; Griaznov, G M; Zhemchuzhnikov, G N; Kiselev, I M; Osipov, A P

    1983-02-01

    An atomic artificial heart for orthotopic implantation was developed with the following characteristics: volume, 1.2 L; weight, 1.5 kg; radioisotope power, 45 W; operating life, up to 5 years; hemodynamics, similar to natural hemodynamics. The artificial heart includes a thermal drive with systems for regulating power, feeding steam into the cylinders, return of the condensate to the steam generator, and delivery of power to the ventricles and heat container. The artificial heart is placed in an artificial pericardium partially filled with physiologic solution. It uses a steam engine with two operating cylinders that separately drive the left and right ventricles. There is no electronic control system in the proposed design. The operation of the heat engine is controlled, with preservation of autoregulation by the vascular system of the body. The separate drives for the ventricles is of primary importance as it provides for operation of the artificial heart through control of cardiac activity by venous return. Experimental testing on a hydromechanical bench demonstrated effective autoregulation.

  7. NASA's Radioisotope Power Systems - Plans

    NASA Technical Reports Server (NTRS)

    Hamley, John A.; Mccallum, Peter W.; Sandifer, Carl E., II; Sutliff, Thomas J.; Zakrajsek, June F.

    2015-01-01

    NASA's Radioisotope Power Systems (RPS) Program continues to plan and implement content to enable planetary exploration where such systems could be needed, and to prepare more advanced RPS technology for possible infusion into future power systems. The 2014-2015 period saw significant changes, and strong progress. Achievements of near-term objectives have enabled definition of a clear path forward in which payoffs from research investments and other sustaining efforts can be applied. The future implementation path is expected to yield a higher-performing thermoelectric generator design, a more isotope-fuel efficient system concept design, and a robust RPS infrastructure maintained effectively within both NASA and the Department of Energy. This paper describes recent work with an eye towards the future plans that result from these achievements.

  8. Linear accelerator for radioisotope production

    SciTech Connect

    Hansborough, L.D.; Hamm, R.W.; Stovall, J.E.

    1982-02-01

    A 200- to 500-..mu..A source of 70- to 90-MeV protons would be a valuable asset to the nuclear medicine program. A linear accelerator (linac) can achieve this performance, and it can be extended to even higher energies and currents. Variable energy and current options are available. A 70-MeV linac is described, based on recent innovations in linear accelerator technology; it would be 27.3 m long and cost approx. $6 million. By operating the radio-frequency (rf) power system at a level necessary to produce a 500-..mu..A beam current, the cost of power deposited in the radioisotope-production target is comparable with existing cyclotrons. If the rf-power system is operated at full power, the same accelerator is capable of producing an 1140-..mu..A beam, and the cost per beam watt on the target is less than half that of comparable cyclotrons.

  9. Radioisotope therapy of cystic craniopharyngeomas

    SciTech Connect

    Strauss, L.; Sturm, V.; Georgi, P.; Schlegel, W.; Ostertag, H.; Clorius, J.H.; Van Kaick, G.

    1982-09-01

    Eighteen patients suffering from cystic craniopharyngeoma were treated with intracavitary irradiation. The beta-emitting radioisotope /sup 90/y (2.25 MeV) was instilled into the cyst following stereotactic puncture of the space-occupying lesion. The surgical approach was planned using angiograms and reconstructed transmission computer tomography (TCT) coronal and saggital sections. Therapy was devised to deliver 20,000 rad to the cyst's wall. Eleven patients received follow-up TCT examinations after four months. Eight of 11 patients had a significant volume decrease in the craniopharyngeoma cyst. In two patients, the cystic volume remained unchanged; one had progression of disease. It is concluded that the intracavitary treatment of cystic craniopharyngeoma will result in a reduction of the size of the space-occupying lesion.

  10. BEST medical radioisotope production cyclotrons

    SciTech Connect

    Sabaiduc, Vasile; Milton, Bruce; Suthanthiran, Krishnan; Johnson, Richard R.; Gelbart, W. Z.

    2013-04-19

    Best Cyclotron Systems Inc (BCSI) is currently developing 14 MeV, 25 MeV, 35MeV and 70MeV cyclotrons for radioisotope production and research applications as well as the entire spectrum of targets and nuclear synthesis modules for the production of Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and radiation therapy isotopes. The company is a subsidiary of Best Medical International, renowned in the field of medical instrumentation and radiation therapy. All cyclotrons have external negative hydrogen ion sources, four radial sectors with two dees in opposite valleys, cryogenic vacuum system and simultaneous beam extraction on opposite lines. The beam intensity ranges from 400 {mu}A to 1000 {mu}A, depending on the cyclotron energy and application.

  11. BEST medical radioisotope production cyclotrons

    NASA Astrophysics Data System (ADS)

    Sabaiduc, Vasile; Milton, Bruce; Suthanthiran, Krishnan; Gelbart, W. Z.; Johnson, Richard R.

    2013-04-01

    Best Cyclotron Systems Inc (BCSI) is currently developing 14 MeV, 25 MeV, 35MeV and 70MeV cyclotrons for radioisotope production and research applications as well as the entire spectrum of targets and nuclear synthesis modules for the production of Positron Emission Tomography (PET), Single Photon Emission Computed Tomography (SPECT) and radiation therapy isotopes. The company is a subsidiary of Best Medical International, renowned in the field of medical instrumentation and radiation therapy. All cyclotrons have external negative hydrogen ion sources, four radial sectors with two dees in opposite valleys, cryogenic vacuum system and simultaneous beam extraction on opposite lines. The beam intensity ranges from 400 μA to 1000 μA, depending on the cyclotron energy and application [1].

  12. Cocktail Therapy of 177Lu-PSMA-617 and 177Lu-EDTMP in Patients With mCRPC: A Proof-of-Principle Application.

    PubMed

    Bal, Chandrasekhar; Yadav, Madhav Prasad; Ballal, Sanjana

    2016-08-01

    Prostate cancer is the second most common primary tumor affecting men worldwide. Among them, 10-20% develop castration resistant prostate cancer (CRPC). Ga-PSMA-PET/CT is an important theranostic agent for the evaluation of CRPC to assess the feasibility of treatment with Lu-PSMA-617 which is a novel therapeutic agent. Interestingly, in certain cases, we have observed non-PSMA-avid lesions despite raised sPSA levels. In this regard, we present a case of cocktail therapy applied using Lu-PSMA-617 and Lu-EDTMP therapy in a 38-year-old male CRPC patient with both soft tissue and extensive skeletal metastases.

  13. US Department of Energy radioisotope customers with summary of radioisotope shipments, FY 1988

    SciTech Connect

    Van Houten, N.C.

    1989-06-01

    Pacific Northwest Laboratory (PNL) prepared this edition of the radioisotope customer list at the request of the Office of Health and Environmental Research (ER-73), Office of Energy Research, US Department of Energy (DOE). This is the 25th report in a series dating from 1964. This report covers DOE radioisotope sales and distribution activities by its facilities to domestic, foreign and other DOE facilities for FY 1988. The report is divided into five sections: radioisotope suppliers, facility contacts, and radioisotopes or services supplied; a list of customers, suppliers, and radioisotopes purchased; a list of radioisotopes purchased cross-referenced to customer numbers; geographic locations of radioisotope customers; and radioisotope sales and transfers -- FY 1988. Radioisotopes not previously reported in this series of reports were argon-37, arsenic-72, arsenic-73, bismuth-207, gadolinium-151, rhenium-188, rhodium-101, selenium-72, xenon-123 and zirconium-88. The total value of DOE radioisotope sales for FY 1988 was $11.1 million, an increase of 3% from FY 1987.

  14. Generation of Radioisotopes with Accelerator Neutrons by Deuterons

    NASA Astrophysics Data System (ADS)

    Nagai, Yasuki; Hashimoto, Kazuyuki; Hatsukawa, Yuichi; Saeki, Hideya; Motoishi, Shoji; Sato, Nozomi; Kawabata, Masako; Harada, Hideo; Kin, Tadahiro; Tsukada, Kazuaki; Sato, Tetsuya K.; Minato, Futoshi; Iwamoto, Osamu; Iwamoto, Nobuyuki; Seki, Yohji; Yokoyama, Kenji; Shiina, Takehiko; Ohta, Akio; Takeuchi, Nobuhiro; Kawauchi, Yukimasa; Sato, Norihito; Yamabayashi, Hisamichi; Adachi, Yoshitsugu; Kikuchi, Yuji; Mitsumoto, Toshinori; Igarashi, Takashi

    2013-06-01

    A new system proposed for the generation of radioisotopes with accelerator neutrons by deuterons (GRAND) is described by mainly discussing the production of 99Mo used for nuclear medicine diagnosis. A prototype facility of this system consists of a cyclotron to produce intense accelerator neutrons from the \\text{natC(d,n) reaction with 40 MeV 2 mA deuteron beams, and a sublimation system to separate \\text{99mTc from an irradiated 100MoO3 sample. About 8.1 TBq/week of 99Mo is produced by repeating irradiation on an enriched 100Mo sample (251 g) with accelerator neutrons for two days three times. It meets about 10% of the 99Mo demand in Japan. The characteristic feature of the system lies in its capability to reliably produce a wide variety of high-quality, carrier-free, carrier-added radioisotopes with a minimum level of radioactive waste without using uranium. The system is compact in size, and easy to operate; therefore it could be used worldwide to produce radioisotopes for medical, research, and industrial applications.

  15. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1983

    SciTech Connect

    Baker, D.A.

    1984-08-01

    This document lists DOE's radioisotope production and distribution activities by its facilities at Argonne National Laboratory; Pacific Northwest Laboratory; Idaho Operations Office; Los Alamos National Laboratory; Oak Ridge National Laboratory; Savannah River Plant; and UNC Nuclear Industries, Inc. The information is divided into five sections: isotope suppliers, facility contacts, and isotopes or services supplied; lists of customers, suppliers and isotopes purchased; list of isotopes purchased cross-referenced to customer codes; geographic locations of radioisotope customers; and radioisotope sales and transfers - FY 1983.

  16. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1986

    SciTech Connect

    Lamar, D.A.

    1987-10-01

    This document describes radioisotope distribution from DOE facilities to private firms including foreign and other DOE facilities. The information is divided into five sections: (1)isotope suppliers, facility contact, and isotopes or services supplied; (2) customers, suppliers, and isotopes purchased; (3) isotopes purchased cross-referenced with customer numbers; (4) geographic locations of radioisotope customers; and (5) radioisotope sales and transfers for fiscal year 1986.

  17. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1987

    SciTech Connect

    Lamar, D.A.; Van Houten, N.C.

    1988-08-01

    This edition of the radioisotope customer list was prepared at the request of the Office of Health and Environmental Research (ER-73), Office of Energy Research, US Department of Energy (DOE). This document describes radioisotope distribution from DOE facilities to private firms, including foreign and other DOE facilities. The information is divided into five sections: 1) isotope suppliers, facility contact, and isotopes or services supplied; 2) customers, suppliers, and isotopes purchased; 3) isotopes purchased cross- referenced with customer numbers; 4) geographic locations of radioisotope customers; and 5) radioisotope sales and transfers for fiscal year 1987.

  18. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1984

    SciTech Connect

    Baker, D.A.

    1985-08-01

    This edition of the radioisotope customer list was prepared at the request of the Office of Health and Environmental Research (ER-73), Office of Energy Research, Department of Energy (DOE). This document describes radioisotope distribution from DOE facilities to private firms including foreign and other DOE facilities. The information is divided into five sections: (1) isotope suppliers, facility contacts, and isotopes or services supplied; (2) customers, suppliers, and isotopes purchased; (3) isotopes purchased cross-referenced with customer numbers; (4) geographic locations of radioisotope customers; and (5) radioisotope sales and transfers - FY 1984.

  19. Advanced Radioisotope Power Systems Segmented Thermoelectric Research

    NASA Technical Reports Server (NTRS)

    Caillat, Thierry

    2004-01-01

    Flight times are long; - Need power systems with >15 years life. Mass is at an absolute premium; - Need power systems with high specific power and scalability. 3 orders of magnitude reduction in solar irradiance from Earth to Pluto. Nuclear power sources preferable. The Overall objective is to develop low mass, high efficiency, low-cost Advanced Radioisotope Power System with double the Specific Power and Efficiency over state-of-the-art Radioisotope Thermoelectric Generators (RTGs).

  20. Radioisotope thermoelectric generators for implanted pacemakers

    SciTech Connect

    Pustovalov, A.A.; Bovin, A.V.; Fedorets, V.I.; Shapovalov, V.P.

    1986-08-01

    This paper discusses the development and application of long-life lithium batteries and the problems associated with miniature radioisotope thermoelectric generators (RITEG) with service lives of 10 years or longer. On eof the main problems encountered when devising a radioisotope heat source (RHS) for an RITEG is to obtain biomedical /sup 238/PuO/sub 2/ with a specific neutron yield of 3.10/sup 3/-4.10/sup 3/ (g /SUP ./ sec)/sup -1/, equivalent to metallic Pu 238, and with a content of gamma impurities sufficient to ensure a permissible exposure a permissible exposure does rate (EDR) of a mixture of neutron and gamma radiation. After carrying out the isotope exchange and purifying the initial sample of its gamma impurity elements, the authors obtain biomedical Pu 238 satisfying the indicated requirements king suitable for use in the power packs of medical devices. Taking the indicated specifications into account, the Ritm-1o and gamma radioisotope heat sources were designed, built, tested in models and under natural conditions, and then into production as radioisotope thermoelectric generators designed to power the electronic circuits of implanted pacemakers. The Ritm-MT and Gemma radioisotope thermoelectric generators described are basic units, which can be used as self-contained power supplies for electronic equipment with power requirements in the micromilliwatt range.

  1. An alternate approach to the production of radioisotopes for nuclear medicine applications.

    PubMed

    D'Auria, John M; Keller, Roderich; Ladouceur, Keith; Lapi, Suzanne E; Ruth, Thomas J; Schmor, Paul

    2013-03-01

    There is a growing need for the production of radioisotopes for both diagnostic and therapeutic medical applications. Radioisotopes that are produced using the (n,γ) or (γ,n) reactions, however, typically result in samples with low specific activity (radioactivity∕gram) due to the high abundance of target material of the same element. One method to effectively remove the isotopic impurity is electro-magnetic mass separation. An Ion Source Test Facility has been constructed at TRIUMF to develop high-intensity, high-efficiency, reliable ion sources for purification of radioactive isotopes, particularly those used in nuclear medicine. In progress studies are presented.

  2. An alternate approach to the production of radioisotopes for nuclear medicine applications

    NASA Astrophysics Data System (ADS)

    D'Auria, John M.; Keller, Roderich; Ladouceur, Keith; Lapi, Suzanne E.; Ruth, Thomas J.; Schmor, Paul

    2013-03-01

    There is a growing need for the production of radioisotopes for both diagnostic and therapeutic medical applications. Radioisotopes that are produced using the (n,γ) or (γ,n) reactions, however, typically result in samples with low specific activity (radioactivity/gram) due to the high abundance of target material of the same element. One method to effectively remove the isotopic impurity is electro-magnetic mass separation. An Ion Source Test Facility has been constructed at TRIUMF to develop high-intensity, high-efficiency, reliable ion sources for purification of radioactive isotopes, particularly those used in nuclear medicine. In progress studies are presented.

  3. Parametric Study of Radiator Concepts for a Stirling Radioisotope Power System Applicable to Deep Space Mission

    NASA Technical Reports Server (NTRS)

    Juhasz, Albert J.; Tew, Roy C.; Thieme, Lanny G.

    2000-01-01

    The Department of Energy (DOE) and the NASA Glenn Research Center are developing a Stirling converter for an advanced radioisotope power system to provide spacecraft onboard electric power for NASA deep space missions. This high-efficiency converter is being evaluated as an alternative to replace the much lower efficiency radioisotope thermoelectric generator (RTG). The current power requirement (six years after beginning of mission (BOM) for a mission to Jupiter) is 210 W(sub e) (watts electric) to be generated by two separate power systems, one on each side of the spacecraft. Both two-converter and four-converter system designs are being considered, depending on the amount of required redundancy.

  4. NASA's Radioisotope Power Systems Program Status

    NASA Technical Reports Server (NTRS)

    Dudzinski, Leonard A.; Hamley, John A.; McCallum, Peter W.; Sutliff, Thomas J.; Zakrajsek, June F.

    2013-01-01

    NASA's Radioisotope Power Systems (RPS) Program began formal implementation in December 2010. The RPS Program's goal is to make available RPS for the exploration of the solar system in environments where conventional solar or chemical power generation is impractical or impossible to meet mission needs. To meet this goal, the RPS Program manages investments in RPS system development and RPS technologies. The current keystone of the RPS Program is the development of the Advanced Stirling Radioisotope Generator (ASRG). This generator will be about four times more efficient than the more traditional thermoelectric generators, while providing a similar amount of power. This paper provides the status of the RPS Program and its related projects. Opportunities for RPS generator development and targeted research into RPS component performance enhancements, as well as constraints dealing with the supply of radioisotope fuel, are also discussed in the context of the next ten years of planetary science mission plans.

  5. Progress on 241Am Production for Use in Radioisotope Power Systems

    NASA Astrophysics Data System (ADS)

    Baker, S. R.; Bell, K. J.; Brown, J.; Carrigan, C.; Carrott, M. J.; Gregson, C.; Clough, M.; Maher, C. J.; Mason, C.; Rhodes, C. J.; Rice, T. G.; Sarsfield, M. J.; Stephenson, K.; Taylor, R. J.; Tinsley, T. P.; Woodhead, D. A.; Wiss, T.

    2014-08-01

    Electrical power sources used in outer planet missions are a key enabling technology for data acquisition and communications. Power sources generate electricity from the thermal energy from alpha decay of the radioisotope 238Pu via thermo-electric conversion. Production of 238Pu requires specialist facilities including a nuclear reactor and reprocessing plants that are expensive to build and operate, so naturally, a more economical alternative is attractive to the industry. Within Europe 241Am is a feasible alternative to 238Pu that can provide a heat source for radioisotope thermoelectric generators (RTGs) and radioisotope heating units (RHUs). As a daughter product of 241Pu decay, 241Am is present at 1000s kg levels within the UK civil plutonium stockpile.A chemical separation process is required to extract the 241Am in a pure form and this paper describes such a process, successfully developed to the proof of concept stage.

  6. Commercial Superconducting Electron Linac for Radioisotope Production

    SciTech Connect

    Grimm, Terry Lee; Boulware, Charles H.; Hollister, Jerry L.; Jecks, Randall W.; Mamtimin, Mayir; Starovoitova, Valeriia

    2015-08-13

    The majority of radioisotopes used in the United States today come from foreign suppliers or are generated parasitically in large government accelerators and nuclear reactors. Both of these restrictions limit the availability of radioisotopes and discourage the development and evaluation of new isotopes and for nuclear medicine, science, and industry. Numerous studies have been recommending development of dedicated accelerators for production of radioisotopes for over 20 years (Institute of Medicine, 1995; Reba, et al, 2000; National Research Council, 2007; NSAC 2009). The 2015 NSAC Long Range Plan for Isotopes again identified electron accelerators as an area for continued research and development. Recommendation 1(c) from the 2015 NSAC Isotope report specifically identifies electron accelerators for continued funding for the purpose of producing medical and industrial radioisotopes. Recognizing the pressing need for new production methods of radioisotopes, the United States Congress passed the American Medical Isotope Production Act of 2012 to develop a domestic production of 99Mo and to eliminate the use of highly enriched uranium (HEU) in the production of 99Mo. One of the advantages of high power electron linear accelerators (linacs) is they can create both proton- and neutron-rich isotopes by generating high energy x-rays that knock out protons or neutrons from stable atoms or by fission of uranium. This allows for production of isotopes not possible in nuclear reactors. Recent advances in superconducting electron linacs have decreased the size and complexity of these systems such that they are economically competitive with nuclear reactors and large, high energy accelerators. Niowave, Inc. has been developing a radioisotope production facility based on a superconducting electron linac with liquid metal converters.

  7. Chemistry of Cosmogenic Radioisotopes in the Stratosphere

    NASA Astrophysics Data System (ADS)

    Rowland, F. S.

    2003-12-01

    Bombardment of Earth's atmosphere by Gev cosmic ray protons produces two neutrons/cm2/second, which react with 14N nuclei to form 14C. The initial stratospheric reaction of the bare 14C atom with O2 forms 14CO, which is subsequently oxidized to 14CO2 by HO. The 14CO2 is then the basis for age-dating studies of inorganic carbon, and of organic carbon after incorporation by photosynthesis. Proton spallation of light nuclei (chiefly 14N, 16O) produces various isotopic fragments, many of them radioactive, containing 8 or fewer protons and 10 or fewer neutrons. For geophysical studies, the most important of the radioisotopes so produced are 3H, 7Be, and 10Be. Proton spallation of 40Ar produces many isotopes with atomic weight less than 40, including 34Cl, 36Cl, 38Cl, 39Cl, 35S, 38S, 22Na, 24Na, 32Si, 32P, and 33P, all of which have been detected in the atmosphere. The "million year" isotopes (10Be, 36Cl) are useful for geological dating. The short-lived isotopes were collected both from rainwater captured at ground level, and on filter paper at 18 kilometers altitude carried by an RB-57 aircraft (1970, J. A. Young, C. W. Thomas, N. A. Wogman and R. W. Perkins, JGR, 75, 2385). The radioisotopes were measured with multidimensional gamma ray spectroscopy, which was able to detect 24Na and 38Cl without prior chemical separation. Count rates as low as 0.1 count/minute were monitored, even in the presence of 107 counts/minute of fallout fission products from nuclear testing in the atmosphere. This fallout background is now greatly reduced because of the four decades old ban on nuclear testing in the atmosphere. The stratospheric collection of 24Na (15 hour half-life) was interpreted as scavenging of the radiosodium by particulate matter, and retention on filter paper with an efficiency of 100 percent within the statistical accuracy in comparison with its production in argon tanks carried on the aircraft. The efficiency of collection of radiochlorine atoms was only about 1

  8. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1982

    SciTech Connect

    Richards, M.P.

    1983-08-01

    The radioisotope production and distribution activities by facilities at Argonne National Laboratory, Pacific Northwest Laboratory, Brookhaven National Laboratory, Hanford Engineering Development Laboratory, Idaho Operations Office, Los Alamos Scientific Laboratory, Oak Ridge National Laboratory, Savannah River Laboratory, and UNC Nuclear Industries, Inc. are listed. The information is divided into five sections: isotope suppliers, facility, contacts, and isotopes or services supplied; alphabetical list of customers, and isotopes purchased; alphabetical list of isotopes cross-referenced to customs numbers; geographical location of radioisotope customers; and radioisotope sales and transfers-FY 1982. (MHR)

  9. The radioisotope complex project "RIC-80" at the Petersburg Nuclear Physics Institute.

    PubMed

    Panteleev, V N; Barzakh, A E; Batist, L Kh; Fedorov, D V; Ivanov, V S; Moroz, F V; Molkanov, P L; Orlov, S Yu; Volkov, Yu M

    2015-12-01

    The high current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed at Petersburg Nuclear Physics Institute. One of the main goals of the C-80 is the production of a wide spectrum of medical radionuclides for diagnostics and therapy. The project development of the radioisotope complex RIC-80 (radioisotopes at the cyclotron C-80) at the beam of C-80 has been completed. The RIC-80 complex is briefly discussed in this paper. The combination of the mass-separator with the target-ion source device, available at one of the new target stations for on-line or semi on-line production of a high purity separated radioisotopes, is explored in greater detail. The results of target and ion source tests for a mass-separator method for the production of high purity radioisotopes (82)Sr and (223,224)Ra are also presented.

  10. The radioisotope complex project “RIC-80” at the Petersburg Nuclear Physics Institute

    SciTech Connect

    Panteleev, V. N. Barzakh, A. E.; Batist, L. Kh.; Fedorov, D. V.; Ivanov, V. S.; Moroz, F. V.; Molkanov, P. L.; Orlov, S. Yu.; Volkov, Yu. M.

    2015-12-15

    The high current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed at Petersburg Nuclear Physics Institute. One of the main goals of the C-80 is the production of a wide spectrum of medical radionuclides for diagnostics and therapy. The project development of the radioisotope complex RIC-80 (radioisotopes at the cyclotron C-80) at the beam of C-80 has been completed. The RIC-80 complex is briefly discussed in this paper. The combination of the mass-separator with the target-ion source device, available at one of the new target stations for on-line or semi on-line production of a high purity separated radioisotopes, is explored in greater detail. The results of target and ion source tests for a mass-separator method for the production of high purity radioisotopes {sup 82}Sr and {sup 223,224}Ra are also presented.

  11. The radioisotope complex project "RIC-80" at the Petersburg Nuclear Physics Institute

    NASA Astrophysics Data System (ADS)

    Panteleev, V. N.; Barzakh, A. E.; Batist, L. Kh.; Fedorov, D. V.; Ivanov, V. S.; Moroz, F. V.; Molkanov, P. L.; Orlov, S. Yu.; Volkov, Yu. M.

    2015-12-01

    The high current cyclotron C-80 capable of producing 40-80 MeV proton beams with a current of up to 200 μA has been constructed at Petersburg Nuclear Physics Institute. One of the main goals of the C-80 is the production of a wide spectrum of medical radionuclides for diagnostics and therapy. The project development of the radioisotope complex RIC-80 (radioisotopes at the cyclotron C-80) at the beam of C-80 has been completed. The RIC-80 complex is briefly discussed in this paper. The combination of the mass-separator with the target-ion source device, available at one of the new target stations for on-line or semi on-line production of a high purity separated radioisotopes, is explored in greater detail. The results of target and ion source tests for a mass-separator method for the production of high purity radioisotopes 82Sr and 223,224Ra are also presented.

  12. Investigation of the excitation functions for some medical radioisotopes production

    NASA Astrophysics Data System (ADS)

    Kılınç, Fatma; Karpuz, Nurdan; Çetin, Betül

    2016-11-01

    One of the main application fields of nuclear technology is medicine and radioisotopes are used in medicine. Production of those radioisotopes is important and in the production processes the cross section must be known. All the production of radioisotope used in medicine is based on the nuclear reactions means they are not natural. The decay time of produced radioisotopes is important as from production to hospital can take time and thus generally generator is used to produce some radioisotopes. Radioisotopes are widely produced in reactors or cyclotron type accelerator. Type of radioisotopes direct way to be used in production processes. Thus obtaining of cross section becomes crucial. For this purposes the theoretical calculation cross section of some radioisotopes used in medicine will be calculated in this study. The calculations will be done using Monte Carlo code of TALYS 1.6

  13. Accelerator Generation and Thermal Separation (AGATS) of Technetium-99m

    SciTech Connect

    2010-01-01

    Accelerator Generation and Thermal Separation (AGATS) of Technetium-99m is a linear electron accelerator-based technology for producing medical imaging radioisotopes from a separation process that heats, vaporizes and condenses the desired radioisotope. You can learn more about INL's education programs at http://www.facebook.com/idahonationallaboratory.

  14. Accelerator Generation and Thermal Separation (AGATS) of Technetium-99m

    ScienceCinema

    None

    2016-07-12

    Accelerator Generation and Thermal Separation (AGATS) of Technetium-99m is a linear electron accelerator-based technology for producing medical imaging radioisotopes from a separation process that heats, vaporizes and condenses the desired radioisotope. You can learn more about INL's education programs at http://www.facebook.com/idahonationallaboratory.

  15. .sup.82 Sr-.sup.82 Rb Radioisotope generator

    DOEpatents

    Grant, Patrick M.; Erdal, Bruce R.; O'Brien, Harold A.

    1976-01-01

    An improved .sup.82 Sr-.sup.82 Rb radioisotope generator system, based upon the complexing ion exchange resin Chelex-100, has been developed. Columns of this material can be easily and rapidly milked, and the Rb-Sr separation factor for a fresh generator was found to be > 10.sup.7. Approximately 80 percent of the .sup.82 Rb present was delivered in a 15-ml volume of aqueous 0.2 M NH.sub.4 Cl solution. After more than 6 liters of eluant had been put through the generator, the Rb-Sr separation factor was still observed to be > 10.sup.5, and no unusual strontium breakthrough behavior was seen in the system over nearly three .sup.82 Sr half lives.

  16. Production of 177Lu, a potential radionuclide for diagnostic and therapeutic applications

    NASA Astrophysics Data System (ADS)

    Khandaker, Mayeen Uddin; Haba, Hiromitsu; Kassim, Hasan Abu

    2015-04-01

    177gLu (T1/2=6.647d; Eβ-max=498.3 KeV, Iβ-total=100 % ; Eγ = 112.9498 keV, Iγ = 6.17%; Eγ = 208.3662 keV, I γ = 10.36%) is widely used in many clinical procedures due to its excellent decay characteristics. Production cross-sections of the natYb(d,x)177gLu reactions have been measured from a 24-MeV deuteron energy down to the threshold by using a stacked-foil activation technique combined with high resolution γ-ray spectrometry. An overall good agreement is found with some of the earlier measurements, whereas a partial agreement is obtained with the theoretical data extracted from the TENDL-2013 library. Physical thick target yield for the 177gLu radionuclide was deduced using the measured cross-sections. The deduced yield curves indicate that a low energy (<11 MeV) cyclotron and a highly enriched 176Yb target could be used to obtain 177gLu with negligible impurity from 177mLu.

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

    SciTech Connect

    Khandaker, Mayeen Uddin; Kassim, Hasan Abu; Haba, Hiromitsu

    2015-04-24

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

  18. Structure and manual of radioisotope-production data base, ISOP

    NASA Astrophysics Data System (ADS)

    Hata, Kentaro; Terunuma, Kusuo

    1994-02-01

    We planned on collecting the information of radioisotope production which was obtained from research works and tasks at the Department of Radioisotopes in JAERI, and constructed a proto-type data base ISOP after discussion of the kinds and properties of the information available for radioisotope production. In this report the structure and the manual of ISOP are described.

  19. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1979

    SciTech Connect

    Burlison, J.S.

    1980-06-01

    The fifteenth edition of the radioisotope customer list was prepared at the request of the Division of Financial Services, Office of the Assistant Secretary for Environment, Department of Energy (DOE). This document lists DOE's radioisotope production and distribution activities by its facilities at Argonne National Laboratory; Pacific Northwest Laboratory; Brookhaven National Laboratory; Hanford Engineering Development Laboratory; Idaho Operations Office; Los Alamos Scientific Laboratory; Mound Facility; Oak Ridge National Laboratory; Rocky Flats Area Office; Savannah River Laboratory; and UNC Nuclear Industries, Inc. The information is divided into five sections: Isotope suppliers, facility, contracts and isotopes or services supplied; alphabetical list of customers, and isotopes purchased; alphabetical list of isotopes cross-referenced to customer numbers; geographical location of radioisotope customers; and radioisotope sales and transfers-FY 1979.

  20. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1981

    SciTech Connect

    Burlison, J.S.

    1982-09-01

    The seventeenth edition of the radioisotope customer list was prepared at the request of the Office of Health and Environmental Research, Office of Energy Research, Department of Energy (DOE). This document lists DOE's radioisotope production and distribution activities by its facilities at Argonne National Laboratory: Pacific Northwest Laboratory; Brookhaven National Laboratory; Hanford Engineering Development Laboratory; Idaho Operations Office; Los Alamos Scientific Laboratory; Mound Facility; Oak Ridge National Laboratory; Savannah River Laboratory; and UNC Nuclear Industries, Inc. The information is divided into five sections: (1) isotope suppliers, facility, contracts and isotopes or services supplied; (2) alphabetical list of customers, and isotopes purchased; (3) alphabetical list of isotopes cross-referenced to customer numbers; (4) geographical location of radioisotope customers; and (5) radioisotope sales and transfers-FY 1980.

  1. List of DOE radioisotope customers with summary of radioisotope shipments, FY 1980

    SciTech Connect

    Burlison, J.S.

    1981-08-01

    The sixteenth edition of the radioisotope customer list was prepared at the request of the Office of Health and Environmental Research, Office of energy Research, Department of Energy (DOE). This document lists DOE's radioisotope production and distribution activities by its facilities at Argonne National Laboratory; Pacific Northwest Laboratory; Brookhaven National Laboraory; Hanford Engineering Development Laboratory; Idaho Operations Office; Los Alamos Scientific Laboratory; Mound Facility; Oak Ridge National Laboratory; Savannah River Laboratory; and UNC Nuclear Industries, Inc. The information is divided into five sections: (1) isotope suppliers, facility, contracts and isotopes or services supplied; (2) alphabetical list of customers, and isotopes purchased; (3) alphabetical list of isotopes cross-referenced to customer numbers; (4) geographical location of radioisotope customers; and (5) radioisotope sales and transfers-FY 1980.

  2. Radioisotopes as Political Instruments, 1946-1953.

    PubMed

    Creager, Angela N H

    2009-01-01

    The development of nuclear "piles," soon called reactors, in the Manhattan Project provided a new technology for manufacturing radioactive isotopes. Radioisotopes, unstable variants of chemical elements that give off detectable radiation upon decay, were available in small amounts for use in research and therapy before World War II. In 1946, the U.S. government began utilizing one of its first reactors, dubbed X-10 at Oak Ridge, as a production facility for radioisotopes available for purchase to civilian institutions. This program of the U.S. Atomic Energy Commission was meant to exemplify the peacetime dividends of atomic energy. The numerous requests from scientists outside the United States, however, sparked a political debate about whether the Commission should or even could export radioisotopes. This controversy manifested the tension in U.S. politics between scientific internationalism as a tool of diplomacy, associated with the aims of the Marshall Plan, and the desire to safeguard the country's atomic monopoly at all costs, linked to American anti-Communism. This essay examines the various ways in which radioisotopes were used as political instruments-both by the U.S. federal government in world affairs, and by critics of the civilian control of atomic energy-in the early Cold War.

  3. Radioisotope thermal generator (RTG) power conditioner

    NASA Technical Reports Server (NTRS)

    Stacey, W. S.

    1974-01-01

    New regulator: (a) permits operation with high-impedance radioisotope thermal generators at conversion efficiencies typically above 90%; (b) does not require input filtering; (c) eliminates current spiking; and (d) is simple, efficient, and reliable. Converter-charger pair could be adapted for other power levels by changing transistor, diode, capacitor bank, and inductor.

  4. NASA Radioisotope Power Conversion Technology NRA Overview

    NASA Technical Reports Server (NTRS)

    Anderson, David J.

    2005-01-01

    The focus of the National Aeronautics and Space Administration's (NASA) Radioisotope Power Systems (RPS) Development program is aimed at developing nuclear power and technologies that would improve the effectiveness of space science missions. The Radioisotope Power Conversion Technology (RPCT) NASA Research Announcement (NRA) is an important mechanism through which research and technology activities are supported in the Advanced Power Conversion Research and Technology project of the Advanced Radioisotope Power Systems Development program. The purpose of the RPCT NRA is to advance the development of radioisotope power conversion technologies to provide higher efficiencies and specific powers than existing systems. These advances would enable a factor of two to four decrease in the amount of fuel and a reduction of waste heat required to generate electrical power, and thus could result in more cost effective science missions for NASA. The RPCT NRA selected advanced RPS power conversion technology research and development proposals in the following three areas: innovative RPS power conversion research, RPS power conversion technology development in a nominal 100 W(sub e) scale; and, milliwatt/multi-watt RPS (mWRPS) power conversion research. Ten RPCT NRA contracts were awarded in 2003 in the areas of Brayton, Stirling, thermoelectric (TE), and thermophotovoltaic (TPV) power conversion technologies. This paper will provide an overview of the RPCT NRA, a summary of the power conversion technologies approaches being pursued, and a brief digest of first year accomplishments.

  5. ILLUSTRATIONS OF RADIOISOTOPES--DEFINITIONS AND APPLICATIONS.

    ERIC Educational Resources Information Center

    Atomic Energy Commission, Oak Ridge, TN. Div. of Technical Information.

    THIS PUBLICATION IS COMPOSED OF OVER 150 PAGES OF BLACK AND WHITE ILLUSTRATIONS DEALING WITH RADIOISOTOPES AND THEIR USES. THESE ILLUSTRATIONS CONSIST OF CHARTS, GRAPHS, AND PICTORIAL REPRESENTATIONS WHICH COULD BE PREPARED AS HANDOUTS, TRANSPARENCIES FOR OVERHEAD PROJECTION, OR WHICH COULD BE USED IN A NUMBER OF OTHER WAYS FOR PRESENTING SUCH…

  6. NASA Radioisotope Power Conversion Technology NRA Overview

    NASA Technical Reports Server (NTRS)

    Anderson, David J.

    2005-01-01

    The focus of the National Aeronautics and Space Administration s (NASA) Radioisotope Power Systems (RPS) Development program is aimed at developing nuclear power and technologies that would improve the effectiveness of space science missions. The Radioisotope Power Conversion Technology (RPCT) NASA Research Announcement (NRA) is an important mechanism through which research and technology activities are supported in the Advanced Power Conversion Research and Technology project of the Advanced Radioisotope Power Systems Development program. The purpose of the RPCT NRA is to advance the development of radioisotope power conversion technologies to provide higher efficiencies and specific powers than existing systems. These advances would enable a factor of 2 to 4 decrease in the amount of fuel and a reduction of waste heat required to generate electrical power, and thus could result in more cost effective science missions for NASA. The RPCT NRA selected advanced RPS power conversion technology research and development proposals in the following three areas: innovative RPS power conversion research, RPS power conversion technology development in a nominal 100We scale; and, milliwatt/multi-watt RPS (mWRPS) power conversion research. Ten RPCT NRA contracts were awarded in 2003 in the areas of Brayton, Stirling, thermoelectric (TE), and thermophotovoltaic (TPV) power conversion technologies. This paper will provide an overview of the RPCT NRA, a summary of the power conversion technologies approaches being pursued, and a brief digest of first year accomplishments.

  7. Radioisotopes as Political Instruments, 1946–1953

    PubMed Central

    Creager, Angela N. H.

    2009-01-01

    The development of nuclear “piles,” soon called reactors, in the Manhattan Project provided a new technology for manufacturing radioactive isotopes. Radioisotopes, unstable variants of chemical elements that give off detectable radiation upon decay, were available in small amounts for use in research and therapy before World War II. In 1946, the U.S. government began utilizing one of its first reactors, dubbed X-10 at Oak Ridge, as a production facility for radioisotopes available for purchase to civilian institutions. This program of the U.S. Atomic Energy Commission was meant to exemplify the peacetime dividends of atomic energy. The numerous requests from scientists outside the United States, however, sparked a political debate about whether the Commission should or even could export radioisotopes. This controversy manifested the tension in U.S. politics between scientific internationalism as a tool of diplomacy, associated with the aims of the Marshall Plan, and the desire to safeguard the country’s atomic monopoly at all costs, linked to American anti-Communism. This essay examines the various ways in which radioisotopes were used as political instruments—both by the U.S. federal government in world affairs, and by critics of the civilian control of atomic energy—in the early Cold War. PMID:20725612

  8. Safety monitoring system for radioisotope thermoelectric generators

    NASA Technical Reports Server (NTRS)

    Zoltan, A.

    1973-01-01

    System alerts personnel of hazards which may develop while they are performing tests on radioisotope thermoelectric generator (RTG). Remedial action is initiated to minimize damage. Five operating conditions are monitored: hot junction temperature, cold junction temperature, thermal shroud coolant flow, vacuum in test chamber, and alpha radiation.

  9. Radioisotopes in management of metastatic prostate cancer

    PubMed Central

    Raval, Amar; Dan, Tu D.; Williams, Noelle L.; Pridjian, Andrew; Den, Robert B.

    2016-01-01

    Introduction: Metastatic prostate cancer continues to be a leading cause of morbidity and mortality in men with prostate cancer. Over the last decade, the treatment landscape for patients with castrate-resistant disease has drastically changed, with several novel agents demonstrating an improvement in overall survival in large, multi-institutional randomized trials. Traditional treatment with radioisotopes has largely been in the palliative setting. However, the first in class radiopharmaceutical radium-223 has emerged as the only bone-directed treatment option demonstrating an improvement in overall survival. Methods: Medline publications from 1990 to 2016 were searched and reviewed to assess the use of currently approved radioisotopes in the management of prostate cancer including emerging data regarding integration with novel systemic therapies. New positron emission tomography-based radiotracers for advanced molecular imaging of prostate cancer were also queried. Results: Radioisotopes play a crucial role in the diagnosis and treatment of prostate cancer in the definitive and metastatic setting. Molecular imaging of prostate cancer and theranostics are currently being investigated in the clinical arena. Conclusions: The use of modern radioisotopes in selected patients with mCRPC is associated with improvements in overall survival, pain control, and quality of life. PMID:27843209

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

    SciTech Connect

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

    1995-12-31

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

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

    PubMed

    Couto, R M; De Barboza, M F; De Souza, A A; Muramoto, E; Mengatti, J; De Araújo, E B

    2010-05-10

    Radyosinovectomy (RSV) is a radiotherapeutic modality where a beta-emitting radionuclide is administered locally by intra-articular injection on the form of a colloid or radiolabeled particulate. RSV is a well-accepted therapeutic procedure in inflammatory joint diseases and has been successfully employed for more than 50 years as a viable alternative to surgical and chemical synovectomy. The aim of this work is to compare the in vivo stability of hydroxyapatite labelled with (177)Lu, (90)Y and (153)Sm. All radionuclides were labelled with high yield and were retained in the joint for 7 days, showing stability and usefulness as tools in the RSV treatment. A similar retention of the products in the muscle was observed when the particles were administrated in the muscle. However, the pure form of the radionuclides were rapidly cleared from the blood and accumulated in the liver when injected i.v.. Although (153)Sm-HA is already available for nuclear medicine procedures and clinical studies with (90)Y-HA have been developed, (177)Lu-labeled RSV agents will be economically more viable and has not been studied yet. Its favorable characteristics contribute to follow, to predict and asses the success of RSV by bone scintigraphy studies.

  12. Alternative Radioisotopes for Heat and Power Sources

    NASA Astrophysics Data System (ADS)

    Tinsley, T.; Sarsfield, M.; Rice, T.

    Production of 238Pu requires considerable facilities including a nuclear reactor and reprocessing plants that are very expensive to build and operate. Thus, a more economical alternative is very attractive to the industry. There are many alternative radioisotopes that exist but few that satisfy the criteria of performance, availability and cost to produce. Any alternative to 238Pu must exist in a chemical form that is compatible with the materials required to safely encapsulate the heat source at the high temperatures of operation and potential launch failure scenarios. The chemical form must also have suitable thermal properties to ensure maximum energy conversion efficiencies when integrated into radioisotope thermoelectric generators over the required mission durations. In addition, the radiation dose must be low enough for operators during production and not so prohibitive that excessive shielding mass is required on the space craft. This paper will focus on the preferred European alternative of 241Am, and the issues that will need to be addressed.

  13. Advanced Stirling Radioisotope Generator Life Certification Plan

    NASA Technical Reports Server (NTRS)

    Rusick, Jeffrey J.; Zampino, Edward J.

    2013-01-01

    An Advanced Stirling Radioisotope Generator (ASRG) power supply is being developed by the Department of Energy (DOE) in partnership with NASA for potential future deep space science missions. Unlike previous radioisotope power supplies for space exploration, such as the passive MMRTG used recently on the Mars Curiosity rover, the ASRG is an active dynamic power supply with moving Stirling engine mechanical components. Due to the long life requirement of 17 years and the dynamic nature of the Stirling engine, the ASRG project faced some unique challenges trying to establish full confidence that the power supply will function reliably over the mission life. These unique challenges resulted in the development of an overall life certification plan that emphasizes long-term Stirling engine test and inspection when analysis is not practical. The ASRG life certification plan developed is described.

  14. Advanced Stirling Radioisotope Generator Life Certification Plan

    NASA Technical Reports Server (NTRS)

    Rusick, Jeffrey J.; Zampino, Edward

    2013-01-01

    An Advanced Stirling Radioisotope Generator (ASRG) power supply is being developed by the Department of Energy (DOE) in partnership with NASA for potential future deep space science missions. Unlike previous radioisotope power supplies for space exploration, such as the passive MMRTG used recently on the Mars Curiosity rover, the ASRG is an active dynamic power supply with moving Stirling engine mechanical components. Due to the long life requirement of 17 years and the dynamic nature of the Stirling engine, the ASRG project faced some unique challenges trying to establish full confidence that the power supply will function reliably over the mission life. These unique challenges resulted in the development of an overall life certification plan that emphasizes long-term Stirling engine test and inspection when analysis is not practical. The ASRG life certification plan developed is described.

  15. Reactors are indispensable for radioisotope production.

    PubMed

    Mushtaq, Ahmad

    2010-12-01

    Radioisotopes can be produced by reactors and accelerators. For certain isotopes there could be an advantage to a certain production method. However, nowadays many reports suggest, that useful isotopes needed in medicine, industry and research could be produced efficiently and dependence on reactors using enriched U-235 may be eliminated. In my view reactors and accelerators will continue to play their role side by side in the supply of suitable and economical sources of isotopes.

  16. NEW DIRECTIONS IN RADIOISOTOPE SPECTRUM IDENTIFICATION

    SciTech Connect

    Salaymeh, S.; Jeffcoat, R.

    2010-06-17

    Recent studies have found the performance of commercial handheld detectors with automatic RIID software to be less than acceptable. Previously, we have explored approaches rooted in speech processing such as cepstral features and information-theoretic measures. Scientific advances are often made when researchers identify mathematical or physical commonalities between different fields and are able to apply mature techniques or algorithms developed in one field to another field which shares some of the same challenges. The authors of this paper have identified similarities between the unsolved problems faced in gamma-spectroscopy for automated radioisotope identification and the challenges of the much larger body of research in speech processing. Our research has led to a probabilistic framework for describing and solving radioisotope identification problems. Many heuristic approaches to classification in current use, including for radioisotope classification, make implicit probabilistic assumptions which are not clear to the users and, if stated explicitly, might not be considered desirable. Our framework leads to a classification approach with demonstrable improvements using standard feature sets on proof-of-concept simulated and field-collected data.

  17. Quantitation of renal function using radioisotopic techniques.

    PubMed

    O'Malley, J P; Ziessman, H A

    1993-03-01

    Radioisotopic methods are practical for clinical use because they do not require continuous intravenous infusion or urine collection. This obviously is of great advantage in infants and small children, in whom accurate urine collection is difficult, but the techniques apply to adults as well. The ability to determine individual kidney function is a major benefit. Accuracies of the radioisotopic techniques vary but generally are within clinically acceptable ranges. The need for accuracy and reproducibility can be balanced with the desire for speed and convenience when choosing among the different techniques. Methods that use plasma sampling provide greater accuracy and are recommended in cases of severe dysfunction, whereas methods such as Gates' camera method, which eliminates plasma samples, can be completed in minutes. Radioisotopic techniques are most useful in the ranges of mild to moderately decreased function, in which serum creatinine concentration is nondiagnostic, and although they are much less accurate at markedly low renal function levels, so is 24-hour creatinine clearance. In conclusion, radiopharmaceutical agents offer a wide array of possible techniques for simple, accurate, and noninvasive measurement of global as well as individual GFR and ERPF.

  18. Diffusion and decay chain of radioisotopes in stagnant water in saturated porous media.

    PubMed

    Guzmán, Juan; Alvarez-Ramirez, Jose; Escarela-Pérez, Rafael; Vargas, Raúl Alejandro

    2014-09-01

    The analysis of the diffusion of radioisotopes in stagnant water in saturated porous media is important to validate the performance of barrier systems used in radioactive repositories. In this work a methodology is developed to determine the radioisotope concentration in a two-reservoir configuration: a saturated porous medium with stagnant water is surrounded by two reservoirs. The concentrations are obtained for all the radioisotopes of the decay chain using the concept of overvalued concentration. A methodology, based on the variable separation method, is proposed for the solution of the transport equation. The novelty of the proposed methodology involves the factorization of the overvalued concentration in two factors: one that describes the diffusion without decay and another one that describes the decay without diffusion. It is possible with the proposed methodology to determine the required time to obtain equal injective and diffusive concentrations in reservoirs. In fact, this time is inversely proportional to the diffusion coefficient. In addition, the proposed methodology allows finding the required time to get a linear and constant space distribution of the concentration in porous mediums. This time is inversely proportional to the diffusion coefficient. In order to validate the proposed methodology, the distributions in the radioisotope concentrations are compared with other experimental and numerical works.

  19. Method for the chemical separation of GE-68 from its daughter Ga-68

    DOEpatents

    Fitzsimmons, Jonathan M.; Atcher, Robert W.

    2010-06-01

    The present invention is directed to a generator apparatus for separating a daughter gallium-68 radioisotope substantially free of impurities from a parent gernanium-68 radioisotope, including a first resin-containing column containing parent gernanium-68 radioisotope and daughter gallium-68 radioisotope, a source of first eluent connected to said first resin-containing column for separating daughter gallium-68 radioisotope from the first resin-containing column, said first eluent including citrate whereby the separated gallium is in the form of gallium citrate, a mixing space connected to said first resin-containing column for admixing a source of hydrochloric acid with said separated gallium citrate whereby gallium citrate is converted to gallium tetrachloride, a second resin-containing column for retention of gallium-68 tetrachloride, and, a source of second eluent connected to said second resin-containing column for eluting the daughter gallium-68 radioisotope from said second resin-containing column.

  20. Establishment of regulation for managing the spent radioisotopes

    SciTech Connect

    Li, K.K.

    1995-12-31

    Along with the increasing finding of the radiation contaminated residential buildings and roads in Taiwan, the appropriate management of the radioisotopes became popular issues recently among the public. This paper described the current situation and inventory of the radioisotopes with traceable records. The author addressed the importance of integrating various regulations to manage the radioisotope during its entire life cycle. A new fee-collecting system was also proposed to implement the generator-pays principle.

  1. Markets for reactor-produced non-fission radioisotopes

    SciTech Connect

    Bennett, R.G.

    1995-01-01

    Current market segments for reactor produced radioisotopes are developed and reported from a review of current literature. Specific radioisotopes studied in is report are the primarily selected from those with major medical or industrial markets, or those expected to have strongly emerging markets. Relative market sizes are indicated. Special emphasis is given to those radioisotopes that are best matched to production in high flux reactors such as the Advanced Test Reactor (ATR) at the Idaho National Engineering Laboratory or the High Flux Isotope Reactor (HFIR) at the Oak Ridge National Laboratory. A general bibliography of medical and industrial radioisotope applications, trends, and historical notes is included.

  2. Spark Plasma Sintering of simulated radioisotope materials within tungsten cermets

    NASA Astrophysics Data System (ADS)

    O'Brien, R. C.; Ambrosi, R. M.; Bannister, N. P.; Howe, S. D.; Atkinson, H. V.

    2009-08-01

    A Spark Plasma Sintering (SPS) furnace was used to produce ceramic-metallic sinters (cermets) containing a simulated loading of radioisotope materials. CeO 2 was used to simulate loadings of PuO 2, UO 2 or AmO 2 within tungsten-based cermets due to the similar kinetic properties of these materials, in particular the respective melting points and Gibbs free energies. The work presented demonstrates the capability and suitability of the SPS process for the production of radioisotope encapsulates for nuclear fuels and other applications (including waste disposal and radioisotope power and heat source fabrication) where the mechanical capture of radioisotope materials is required.

  3. Vitrified chemically bonded phosphate ceramics for immobilization of radioisotopes

    DOEpatents

    Wagh, Arun S.

    2016-04-05

    A method of immobilizing a radioisotope and vitrified chemically bonded phosphate ceramic (CBPC) articles formed by the method are described. The method comprises combining a radioisotope-containing material, MgO, a source of phosphate, and optionally, a reducing agent, in water at a temperature of less than 100.degree. C. to form a slurry; curing the slurry to form a solid intermediate CBPC article comprising the radioisotope therefrom; comminuting the intermediate CBPC article, mixing the comminuted material with glass frits, and heating the mixture at a temperature in the range of about 900 to about 1500.degree. C. to form a vitrified CBPC article comprising the radioisotope immobilized therein.

  4. Miniaturized radioisotope solid state power sources

    NASA Astrophysics Data System (ADS)

    Fleurial, J.-P.; Snyder, G. J.; Patel, J.; Herman, J. A.; Caillat, T.; Nesmith, B.; Kolawa, E. A.

    2000-01-01

    Electrical power requirements for the next generation of deep space missions cover a wide range from the kilowatt to the milliwatt. Several of these missions call for the development of compact, low weight, long life, rugged power sources capable of delivering a few milliwatts up to a couple of watts while operating in harsh environments. Advanced solid state thermoelectric microdevices combined with radioisotope heat sources and energy storage devices such as capacitors are ideally suited for these applications. By making use of macroscopic film technology, microgenrators operating across relatively small temperature differences can be conceptualized for a variety of high heat flux or low heat flux heat source configurations. Moreover, by shrinking the size of the thermoelements and increasing their number to several thousands in a single structure, these devices can generate high voltages even at low power outputs that are more compatible with electronic components. Because the miniaturization of state-of-the-art thermoelectric module technology based on Bi2Te3 alloys is limited due to mechanical and manufacturing constraints, we are developing novel microdevices using integrated-circuit type fabrication processes, electrochemical deposition techniques and high thermal conductivity substrate materials. One power source concept is based on several thermoelectric microgenerator modules that are tightly integrated with a 1.1W Radioisotope Heater Unit. Such a system could deliver up to 50mW of electrical power in a small lightweight package of approximately 50 to 60g and 30cm3. An even higher degree of miniaturization and high specific power values (mW/mm3) can be obtained when considering the potential use of radioisotope materials for an alpha-voltaic or a hybrid thermoelectric/alpha-voltaic power source. Some of the technical challenges associated with these concepts are discussed in this paper. .

  5. Analysis of a Radioisotope Thermal Rocket Engine

    NASA Technical Reports Server (NTRS)

    Machado-Rodriguez, Jonathan P.; Landis, Geoffrey A.

    2017-01-01

    The Triton Hopper is a concept for a vehicle to explore the surface of Neptunes moon Triton, which uses a radioisotope heated rocket engine and in-situ propellant acquisition. The initial Triton Hopper conceptual design stores pressurized Nitrogen in a spherical tank to be used as the propellant. The aim of the research was to investigate the benefits of storing propellant at ambient temperature and heating it through a thermal block during engine operation, as opposed to storing gas at a high temperature.

  6. Medical Radioisotope Data Survey: 2002 Preliminary Results

    SciTech Connect

    Siciliano, Edward R.

    2004-06-23

    A limited, but accurate amount of detailed information about the radioactive isotopes used in the U.S. for medical procedures was collected from a local hospital and from a recent report on the U.S. Radiopharmaceutical Markets. These data included the total number of procedures, the specific types of procedures, the specific radioisotopes used in these procedures, and the dosage administered per procedure. The information from these sources was compiled, assessed, pruned, and then merged into a single, comprehensive and consistent set of results presented in this report. (PIET-43471-TM-197)

  7. High efficiency radioisotope thermophotovoltaic prototype generator

    NASA Technical Reports Server (NTRS)

    Avery, James E.; Samaras, John E.; Fraas, Lewis M.; Ewell, Richard

    1995-01-01

    A radioisotope thermophotovoltaic generator space power system (RTPV) is lightweight, low-cost alternative to the present radioisotope thermoelectric generator system (RTG). The fabrication of such an RTPV generator has recently become feasible as the result of the invention of the GaSb infrared sensitive photovoltaic cell. Herein, we present the results of a parametric study of emitters and optical filters in conjuction with existing data on gallium antimonide cells. We compare a polished tungsten emitter with an Erbia selective emitter for use in combination with a simple dielectric filter and a gallium antimonide cell array. We find that the polished tungsten emitter is by itself a very selective emitter with low emissivity beyond 4 microns. Given a gallium antimonide cell and a tungsten emitter, a simple dielectric filter can be designed to transmit radiant energy below 1.7 microns and to reflect radiant energy between 1.7 and 4 microns back to the emitter. Because of the low long wavelength emissivity associated with the polished tungsten emitter, this simple dielectric filter then yields very respectable system performance. Also as a result of the longer wavelength fall-off in the tungsten emissivity curve, the radiation energy peak for a polished tungsten emitter operating at 1300 K shifts to shorter wavelengths relative to the blackbody spectrum so that the radiated energy peak falls right at the gallium antimonide cell bandedge. The result is that the response of the gallium antimonide cell is well matched to a polished tungsten emitter. We propose, therefore, to fabricate an operating prototype of a near term radioisotope thermophotovoltaic generator design consisting of a polished tungsten emitter, standard gallium antimonide cells, and a near-term dielectric filter. The Jet Propulsion Laboratory will design and build the thermal cavity, and JX Crystals will fabricate the gallium antimonide cells, dielectric filters, and resultant receiver panels. With

  8. Science Instrument Sensitivities to Radioisotope Power System Environment

    NASA Technical Reports Server (NTRS)

    Bairstow, Brian; Lee, Young; Smythe, William; Zakrajsek, June

    2016-01-01

    Radioisotope Power Systems (RPS) have been and will be enabling or significantly enhancing for many missions, including several concepts identified in the 2011 Planetary Science Decadal Survey. Some mission planners and science investigators might have concerns about possible impacts from RPS-induced conditions upon the scientific capabilities of their mission concepts. To alleviate these concerns, this paper looks at existing and potential future RPS designs, and examines their potential radiation, thermal, vibration, electromagnetic interference (EMI), and magnetic fields impacts on representative science instruments and science measurements. Radiation impacts from RPS on science instruments are of potential concern for instruments with optical detectors and instruments with high-voltage electronics. The two main areas of concern are noise effects on the instrument measurements, and long-term effects of instrument damage. While RPS by their nature will contribute to total radiation dose, their addition for most missions should be relatively small. For example, the gamma dose rate from one Multi-Mission Radioisotope Thermoelectric Generator (MMRTG) would be an order of magnitude lower than the environmental dose rate at Mars, and would have a correspondingly lower contribution to instrument noise and to any permanent damage to payload sensors. Increasing the number of General Purpose Heat Source (GPHS) modules used in an RPS would be expected to increase the generated radiation proportionally; however, the effect of more GPHS modules is mitigated from a strictly linear relationship by self-shielding effects. The radiation field of an RPS is anisotropic due to the deviation of the modules from a point-source-geometry. For particularly sensitive instruments the total radiation dose could be mitigated with separation or application of spot shielding. Though a new, higher-power RPS could generate more heat per unit than current designs, thermal impact to the flight

  9. Reliability Issues in Stirling Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    Shah, Ashwin R.; Schreiber, Jeffrey G.

    2004-01-01

    Stirling power conversion is a potential candidate for use in a Radioisotope Power System (RPS) for space science missions because it offers a multifold increase in the conversion efficiency of heat to electric power and reduced requirement of radioactive material. Reliability of an RPS that utilizes Stirling power conversion technology is important in order to ascertain long term successful performance. Owing to long life time requirement (14 years), it is difficult to perform long-term tests that encompass all the uncertainties involved in the design variables of components and subsystems comprising the RPS. The requirement for uninterrupted performance reliability and related issues are discussed, and some of the critical areas of concern are identified. An overview of the current on-going efforts to understand component life, design variables at the component and system levels, and related sources and nature of uncertainties are also discussed. Current status of the 110 watt Stirling Radioisotope Generator (SRG110) reliability efforts is described. Additionally, an approach showing the use of past experience on other successfully used power systems to develop a reliability plan for the SRG110 design is outlined.

  10. Preparing for Harvesting Radioisotopes from FRIB

    SciTech Connect

    Peaslee, Graham F.; Lapi, Suzanne E.

    2015-02-02

    The Facility for Rare Isotope Beams (FRIB) is the next generation accelerator facility under construction at Michigan State University. FRIB will produce a wide variety of rare isotopes by a process called projectile fragmentation for a broad range of new experiments when it comes online in 2020. The accelerated rare isotope beams produced in this facility will be more intense than any current facility in the world - in many cases by more than 1000-fold. These beams will be available to the primary users of FRIB in order to do exciting new fundamental research with accelerated heavy ions. In the standard mode of operation, this will mean one radioisotope will be selected at a time for the user. However, the projectile fragmentation process also yields hundreds of other radioisotopes at these bombarding energies, and many of these rare isotopes are long-lived and could have practical applications in medicine, national security or the environment. This project developed new methods to collect these long-lived rare isotopes that are by-products of the standard FRIB operation. These isotopes are important to many areas of research, thus this project will have a broad impact in several scientific areas including medicine, environment and homeland security.

  11. Actinium radioisotope products of enhanced purity

    SciTech Connect

    Meikrantz, David Herbert; Todd, Terry Allen; Tranter, Troy Joseph; Horwitz, E. Philip

    2010-06-15

    A product includes actinium-225 (.sup.225Ac) and less than about 1 microgram (.mu.g) of iron (Fe) per millicurie (mCi) of actinium-225. The product may have a radioisotopic purity of greater than about 99.99 atomic percent (at %) actinium-225 and daughter isotopes of actinium-225, and may be formed by a method that includes providing a radioisotope mixture solution comprising at least one of uranium-233 (.sup.233U) and thorium-229 (.sup.229Th), extracting the at least one of uranium-233 and thorium-229 into an organic phase, substantially continuously contacting the organic phase with an aqueous phase, substantially continuously extracting actinium-225 into the aqueous phase, and purifying the actinium-225 from the aqueous phase. In some embodiments, the product may include less than about 1 nanogram (ng) of iron per millicurie (mCi) of actinium-225, and may include less than about 1 microgram (.mu.g) each of magnesium (Mg), Chromium (Cr), and manganese (Mn) per millicurie (mCi) of actinium-225.

  12. Rhenium Radioisotopes for Therapeutic Radiopharmaceutical Development

    SciTech Connect

    Beets, A.L.; Knapp, F.F., Jr.; Kropp, J.; Lin, W.-Y.; Pinkert, J.; Wang, S.-Y.

    1999-01-18

    The availability of therapeutic radioisotopes at reasonable costs is important for applications in nuclear medicine, oncology and interventional cardiology, Rhenium-186 (Re-186) and rhenium-1 88 (Re-188) are two reactor-produced radioisotope which are attractive for a variety of therapeutic applications, Rhenium-186 has a half-life of 90 hours and decays with emission of a &particle with a maximum energy of 1.08 MeV and a 135 keV (9Yo) gamma which permits imaging. In contrast, Re- 188 has a much shorter half-life of 16.9 hours and emits a p-particle with a much higher energy of 2.12 MeV (Em=) and a 155 keV gamma photon (15Yo) for imaging. While Re-186 is unavailable from a generator system and must be directly produced in a nuclear reactor, Re-188 can also be directly produced in a reactor with high specific activity, but is more conveniently and cost-effectively available as carrier-free sodium perrhenate by saline elution of the alumina-based tungsten-188 (W1 88)/Re-l 88 generator system [1-2]. Since a comprehensive overviewofRe-186 and Re-188 therapeutic agents is beyond the scope of this &tended Abstrac4 the goal is to provide key examples of various agents currently in clinical use and those which are being developed for important clinical applications.

  13. Cosmogenic radioisotopes in Gebel Kamil meteorite

    NASA Astrophysics Data System (ADS)

    Taricco, C.; Colombetti, P.; Bhandari, N.; Sinha, N.; Di Martino, M.; Vivaldo, G.

    2012-04-01

    Recently a small (45 m in diameter) and very young (< 5,000 years) impact crater was discovered in Egypt (Folco et al., 2010, 2011); it was generated by an iron meteorite named Gebel Kamil (Meteoritical Bulletin No. 98, Weisberg et al. 2010). During systematic searches, many specimens were found in the area surrounding the crater. We present the gamma-activity measurement of a 672 g fragment using a highly selective Ge-NaI spectrometer operating at Monte dei Cappuccini Laboratory (IFSI, INAF) in Torino, Italy. This apparatus allows to reveal the radioisotope activity generated by cosmic rays in the meteoroids as they travel through the interplanetary space before falling on the Earth. From the 26Al activity measurement and its depth production profiles, we infer (i) that the radius of the meteoroid should be about 1 m, constraining to 30-40 ton the range of pre-atmospheric mass previously proposed and (ii) that the fragment should have been located deeply inside the meteoroid, at a depth > 0.7 m. The 44Ti activity is under the detection threshold of the apparatus; using the depth production profiles of this radioisotope and its half-life T1/2 = 59.2 y, we deduce an upper limit to the date of fall.

  14. RADIOISOTOPE EXPERIMENTS IN HIGH SCHOOL BIOLOGY, AN ANNOTATED SELECTED BIBLIOGRAPHY.

    ERIC Educational Resources Information Center

    HURLBURT, EVELYN M.

    SELECTED REFERENCES ON THE USE OF RADIOISOTOPES IN BIOLOGY ARE CONTAINED IN THIS ANNOTATED BIBLIOGRAPHY FOR SECONDARY SCHOOL STUDENTS. MATERIALS INCLUDED WERE PUBLISHED AFTER 1960 AND DEAL WITH THE PROPERTIES OF RADIATION, SIMPLE RADIATION DETECTION PROCEDURES, AND TECHNIQUES FOR USING RADIOISOTOPES EXPERIMENTALLY. THE REFERENCES ARE LISTED IN…

  15. Assessment of radioisotope heaters for remote terrestrial applications

    NASA Astrophysics Data System (ADS)

    Uherka, Kenneth L.

    This paper examines the feasibility of using radioisotope byproducts for special heating applications at remote sites in Alaska and other cold regions. The investigation included assessment of candidate radioisotope materials for heater applications, identification of the most promising cold-region applications, evaluation of key technical issues and implementation constraints, and development of conceptual heater designs for candidate applications. Strontium-90 (Sr-90) was selected as the most viable fuel for radioisotopic heaters used in terrestrial applications. Opportunities for the application of radioisotopic heaters were determined through site visits to representative Alaskan installations. Candidate heater applications included water storage tanks, sludge digesters, sewage lagoons, water piping systems, well-head pumping stations, emergency shelters, and fuel storage tank deicers. Radio-isotopic heaters for freeze-up protection of water storage tanks and for enhancement of biological waste treatment processes at remote sites were selected as the most promising applications.

  16. Assessment of radioisotope heaters for remote terrestrial applications

    SciTech Connect

    Uherka, K.L.

    1987-05-01

    This paper examines the feasibility of using radioisotope byproducts for special heating applications at remote sites in Alaska and other cold regions. The investigation included assessment of candidate radioisotope materials for heater applications, identification of the most promising cold region applications, evaluation of key technical issues and implementation constraints, and development of conceptual heater designs for candidate applications. Strontium-90 (Sr-90) was selected as the most viable fuel for radioisotopic heaters used in terrestrial applications. Opportunities for the application of radioisotopic heaters were determined through site visits to representative Alaska installations. Candidate heater applications included water storage tanks, sludge digesters, sewage lagoons, water piping systems, well-head pumping stations, emergency shelters, and fuel storage tank deicers. Radioisotopic heaters for water storage tank freeze-up protection and for enhancement of biological waste treatment processes at remote sites were selected as the most promising applications.

  17. Performance tuned radioisotope thermophotovoltaic space power system

    SciTech Connect

    Horne, W.E.; Morgan, M.D.; Saban, S.B.

    1998-01-01

    The trend in space exploration is to use many small, low-cost, special-purpose satellites instead of the large, high-cost, multipurpose satellites used in the past. As a result of this new trend, there is a need for lightweight, efficient, and compact radioisotope fueled electrical power generators. This paper presents an improved design for a radioisotope thermophotovoltaic (RTPV) space power system in the 10 W to 20 W class which promises up to 37.6 watts at 30.1{percent} efficiency and 25 W/kg specific power. The RTPV power system concept has been studied and compared to radioisotope thermoelectric generators (RTG) radioisotope, Stirling generators and alkali metal thermal electric conversion (AMTEC) generators (Schock, 1995). The studies indicate that RTPV has the potential to be the lightest weight, most efficient and most reliable of the three concepts. However, in spite of the efficiency and light weight, the size of the thermal radiator required to eliminate excess heat from the PV cells and the lack of actual system operational performance data are perceived as obstacles to RTPV acceptance for space applications. Between 1994 and 1997 EDTEK optimized the key converter components for an RTPV generator under Department of Energy (DOE) funding administered via subcontracts to Orbital Sciences Corporation (OSC) and EG&G Mound Applied Technologies Laboratory (Horne, 1995). The optimized components included a resonant micromesh infrared bandpass filter, low-bandgap GaSb PV cells and cell arrays. Parametric data from these components were supplied to OSC who developed and analyzed the performance of 100 W, 20 W, and 10 W RTPV generators. These designs are described in references (Schock 1994, 1995 and 1996). Since the performance of each class of supply was roughly equivalent and simply scaled with size, this paper will consider the OSC 20 W design as a baseline. The baseline 20-W RTPV design was developed by Schock, et al of OSC and has been presented elsewhere

  18. Thermophotovoltaic Converter Design for Radioisotope Power Systems

    SciTech Connect

    Crowley, Christopher J.; Elkouh, Nabil A.; Murray, Susan; Murray, Christopher

    2004-02-04

    The development of lightweight, efficient power for emerging NASA missions and recent advances in thermophotovoltaic (TPV) conversion technology have renewed interest in combining radioisotope heat sources with photovoltaic energy conversion. Thermophotovoltaic power conversion uses advanced materials able to utilize a broader, spectrally tuned range of wavelengths for more efficient power conversion than solar cells. Spectral control, including selective emitters, TPV module, and filters, are key to high-efficiency operation. This paper outlines the mechanical, thermal, and optical designs for the converter, including the heat source, the selective emitter, filters, photovoltaic (PV) cells, and optical cavity components. Focus is on the emitter type and the band-gap of InGaAs PV cells in developing the design. Any component and converter data available at the time of publication will also be presented.

  19. Energy Recovery Linacs for Commercial Radioisotope Production

    SciTech Connect

    Sy, Amy; Krafft, Geoffrey A.; Johnson, Rolland; Roberts, Tom; Boulware, Chase; Hollister, Jerry

    2015-09-01

    Photonuclear reactions with bremsstrahlung photon beams from electron linacs can generate radioisotopes of critical interest. An SRF Energy Recovery Linac (ERL) provides a path to a more diverse and reliable domestic supply of short-lived, high-value, high-demand isotopes in a more compact footprint and at a lower cost than those produced by conventional reactor or ion accelerator methods. Use of an ERL enables increased energy efficiency of the complex through energy recovery of the waste electron beam, high electron currents for high production yields, and reduced neutron production and shielding activation at beam dump components. Simulation studies using G4Beamline/GEANT4 and MCNP6 through MuSim, as well as other simulation codes, will design an ERL-based isotope production facility utilizing bremsstrahlung photon beams from an electron linac. Balancing the isotope production parameters versus energy recovery requirements will inform a choice of isotope production target for future experiments.

  20. Induced radioisotopes in a linac treatment hall.

    PubMed

    Vega-Carrillo, Héctor René; de Leon-Martinez, Héctor Asael; Rivera-Perez, Esteban; Luis Benites-Rengifo, Jorge; Gallego, Eduardo; Lorente, Alfredo

    2015-08-01

    When linacs operate above 8MV an undesirable neutron field is produced whose spectrum has three main components: the direct spectrum due to those neutrons leaking out from the linac head, the scattered spectrum due to neutrons produced in the head that collides with the nuclei in the head losing energy and the third spectrum due to room-return effect. The third category of spectrum has mainly epithermal and thermal neutrons being constant at any location in the treatment hall. These neutrons induce activation in the linac components, the concrete walls and in the patient body. Here the induced radioisotopes have been identified in concrete samples located in the hall and in one of the wedges. The identification has been carried out using a gamma-ray spectrometer.

  1. Collinear laser spectroscopy of radioisotopes of zirconium

    NASA Astrophysics Data System (ADS)

    Thayer, H. L.; Billowes, J.; Campbell, P.; Dendooven, P.; Flanagan, K. T.; Forest, D. H.; Griffith, J. A. R.; Huikari, J.; Jokinen, A.; Moore, R.; Nieminen, A.; Tungate, G.; Zemlyanoi, S.; Äystö, J.

    2003-09-01

    Isotope shifts and hyperfine structures have been measured for radioisotopes of ionic zirconium using on-line laser spectroscopy at the IGISOL facility in Jyväskylä, where the installation of an ion beam cooler/buncher has significantly improved the experimental sensitivity. Measurements have been made on all the neutron-deficient isotopes from 87Zr to 90Zr, including the isomers 87m,89mZr, and the neutron-rich isotopes from 96Zr to 102Zr. The change in mean square charge radii between the isotopes and the nuclear moments of the odd isotopes have been extracted. The data show a sudden increase in the mean square charge radius at mass A = 100, consistent with an onset of nuclear deformation which has been observed in the gamma ray spectroscopy of isotope chains in this region of the nuclear chart.

  2. Radioisotope Power Systems Program: A Program Overview

    NASA Technical Reports Server (NTRS)

    Hamley, John A.

    2016-01-01

    NASA's Radioisotope Power Systems (RPS) Program continues to plan, mature research in energy conversion, and partners with the Department of Energy (DOE) to make RPS ready and available to support the exploration of the solar system in environments where the use of conventional solar or chemical power generation is impractical or impossible to meet potential future mission needs. Recent programs responsibilities include providing investment recommendations to NASA stakeholders on emerging thermoelectric and Stirling energy conversion technologies and insight on NASA investments at DOE in readying a generator for the Mars 2020 mission. This presentation provides an overview of the RPS Program content and status and the approach used to maintain the readiness of RPS to support potential future NASA missions.

  3. Status of the NASA Stirling Radioisotope Project

    NASA Technical Reports Server (NTRS)

    Schreiber, Jeffrey G.

    2007-01-01

    Free-piston Stirling power conversion has been considered a candidate for radioisotope power systems for space for more than a decade. Prior to the free-piston Stirling architecture, systems were designed with kinematic Stirling engines that used linkages and rotary alternators to convert heat to electricity. These systems were able to achieve long life by lightly loading the linkages; however, the live was nonetheless limited. When the free-piston configuration was initially proposed, it was thought to be attractive due to the relatively high conversion efficiency, acceptable mass, and the potential for long life and high reliability based on wear-free operation. These features have consistently been recognized by teams that have studied technology options for radioisotope space power systems. Since free-piston Stirling power conversion was first considered for space power applications, there have been major advances in three general areas of development: hardware that has demonstrated long-life and reliability, the success achieved by Stirling cryocoolers in space, and the overall developmental maturity of the technology for both space and terrestrial applications. Based on these advances, free-piston Stirling convertors are currently being developed for space power, and for a number of terrestrial applications. They commonly operate with the power, efficiency, life, and reliability as intended, and much of the development now centers on system integration. This paper will summarize the accomplishments of free-piston Stirling power conversion technology over the past decade, review the status of development with regard to space power, and discuss the challenges that remain.

  4. Advanced Radioisotope Power Conversion Technology Research and Development

    NASA Technical Reports Server (NTRS)

    Wong, Wayne A.

    2004-01-01

    NASA's Radioisotope Power Conversion Technology program is developing next generation power conversion technologies that will enable future missions that have requirements that cannot be met by either the ubiquitous photovoltaic systems or by current Radioisotope Power System (RPS) technology. Performance goals of advanced radioisotope power systems include improvement over the state-of-practice General Purpose Heat Source/Radioisotope Thermoelectric Generator by providing significantly higher efficiency to reduce the number of radioisotope fuel modules, and increase specific power (watts/kilogram). Other Advanced RPS goals include safety, long-life, reliability, scalability, multi-mission capability, resistance to radiation, and minimal interference with the scientific payload. NASA has awarded ten contracts in the technology areas of Brayton, Stirling, Thermoelectric, and Thermophotovoltaic power conversion including five development contracts that deal with more mature technologies and five research contracts. The Advanced RPS Systems Assessment Team includes members from NASA GRC, JPL, DOE and Orbital Sciences whose function is to review the technologies being developed under the ten Radioisotope Power Conversion Technology contracts and assess their relevance to NASA's future missions. Presented is an overview of the ten radioisotope power conversion technology contracts and NASA's Advanced RPS Systems Assessment Team.

  5. Radioisotope Reduction Using Solar Power for Outer Planetary Missions

    NASA Technical Reports Server (NTRS)

    Fincannon, James

    2008-01-01

    Radioisotope power systems have historically been (and still are) the power system of choice from a mass and size perspective for outer planetary missions. High demand for and limited availability of radioisotope fuel has made it necessary to investigate alternatives to this option. Low mass, high efficiency solar power systems have the potential for use at low outer planetary temperatures and illumination levels. This paper documents the impacts of using solar power systems instead of radioisotope power for all or part of the power needs of outer planetary spacecraft and illustrates the potential fuel savings of such an approach.

  6. Report on audit of funding for advanced radioisotope power systems

    SciTech Connect

    1997-10-17

    The U.S. Department of Energy`s (Department) Advanced Radioisotope Power Systems Program maintains the sole national capability and facilities to produce radioisotope power systems for the National Aeronautics and Space Administration (NASA), the Department of Defense, and other Federal agencies. Projects are conducted with these agencies in accordance with written agreements and are dependent on cost sharing by the user agencies. For the past seven years the program emphasis has been on providing power systems for NASA`s Cassini mission to Saturn, which was launched earlier this month. We initiated this audit to determine whether the Department received proper reimbursement from NASA for the radioisotope power systems produced.

  7. The copper radioisotopes: a systematic review with special interest to 64Cu.

    PubMed

    Niccoli Asabella, Artor; Cascini, Giuseppe Lucio; Altini, Corinna; Paparella, Domenico; Notaristefano, Antonio; Rubini, Giuseppe

    2014-01-01

    Copper (Cu) is an important trace element in humans; it plays a role as a cofactor for numerous enzymes and other proteins crucial for respiration, iron transport, metabolism, cell growth, and hemostasis. Natural copper comprises two stable isotopes, (63)Cu and (65)Cu, and 5 principal radioisotopes for molecular imaging applications ((60)Cu, (61)Cu, (62)Cu, and (64)Cu) and in vivo targeted radiation therapy ((64)Cu and (67)Cu). The two potential ways to produce Cu radioisotopes concern the use of the cyclotron or the reactor. A noncopper target is used to produce noncarrier-added Cu thanks to a chemical separation from the target material using ion exchange chromatography achieving a high amount of radioactivity with the lowest possible amount of nonradioactive isotopes. In recent years, Cu isotopes have been linked to antibodies, proteins, peptides, and nanoparticles for preclinical and clinical research; pathological conditions that influence Cu metabolism such as Menkes syndrome, Wilson disease, inflammation, tumor growth, metastasis, angiogenesis, and drug resistance have been studied. We aim to discuss all Cu radioisotopes application focusing on (64)Cu and in particular its form (64)CuCl2 that seems to be the most promising for its half-life, radiation emissions, and stability with chelators, allowing several applications in oncological and nononcological fields.

  8. Accelerator Mass Spectrometry for Measurement of Long-Lived Radioisotopes

    NASA Astrophysics Data System (ADS)

    Elmore, David; Phillips, Fred M.

    1987-05-01

    Particle accelerators, such as those built for research in nuclear physics, can also be used together with magnetic and electrostatic mass analyzers to measure rare isotopes at very low abundance ratios. All molecular ions can be eliminated when accelerated to energies of millions of electron volts. Some atomic isobars can be eliminated with the use of negative ions; others can be separated at high energies by measuring their rate of energy loss in a detector. The long-lived radioisotopes 10Be, 14C, 26Al, 36Cl, and 129I can now be measured in small natural samples having isotopic abundances in the range 10-12 to 10-15 and as few as 105 atoms. In the past few years, research applications of accelerator mass spectrometry have been concentrated in the earth sciences (climatology, cosmochemistry, environmental chemistry, geochronology, glaciology, hydrology, igneous petrogenesis, minerals exploration, sedimentology, and volcanology), in anthropology and archeology (radiocarbon dating), and in physics (searches for exotic particles and measurement of half-lives). In addition, accelerator mass spectrometry may become an important tool for the materials and biological sciences.

  9. "Stereo Compton cameras" for the 3-D localization of radioisotopes

    NASA Astrophysics Data System (ADS)

    Takeuchi, K.; Kataoka, J.; Nishiyama, T.; Fujita, T.; Kishimoto, A.; Ohsuka, S.; Nakamura, S.; Adachi, S.; Hirayanagi, M.; Uchiyama, T.; Ishikawa, Y.; Kato, T.

    2014-11-01

    The Compton camera is a viable and convenient tool used to visualize the distribution of radioactive isotopes that emit gamma rays. After the nuclear disaster in Fukushima in 2011, there is a particularly urgent need to develop "gamma cameras", which can visualize the distribution of such radioisotopes. In response, we propose a portable Compton camera, which comprises 3-D position-sensitive GAGG scintillators coupled with thin monolithic MPPC arrays. The pulse-height ratio of two MPPC-arrays allocated at both ends of the scintillator block determines the depth of interaction (DOI), which dramatically improves the position resolution of the scintillation detectors. We report on the detailed optimization of the detector design, based on Geant4 simulation. The results indicate that detection efficiency reaches up to 0.54%, or more than 10 times that of other cameras being tested in Fukushima, along with a moderate angular resolution of 8.1° (FWHM). By applying the triangular surveying method, we also propose a new concept for the stereo measurement of gamma rays by using two Compton cameras, thus enabling the 3-D positional measurement of radioactive isotopes for the first time. From one point source simulation data, we ensured that the source position and the distance to the same could be determined typically to within 2 meters' accuracy and we also confirmed that more than two sources are clearly separated by the event selection from two point sources of simulation data.

  10. Accelerator mass spectrometry for measurement of long-lived radioisotopes.

    PubMed

    Elmore, D; Phillips, F M

    1987-05-01

    Particle accelerators, such as those built for research in nuclear physics, can also be used together with magnetic and electrostatic mass analyzers to measure rare isotopes at very low abundance ratios. All molecular ions can be eliminated when accelerated to energies of millions of electron volts. Some atomic isobars can be eliminated with the use of negative ions; others can be separated at high energies by measuring their rate of energy loss in a detector. The long-lived radioisotopes (10)Be, (14)C,(26)A1, 36Cl, and (129)1 can now be measured in small natural samples having isotopic abundances in the range 10(-12) to 10(- 5) and as few as 10(5) atoms. In the past few years, research applications of accelerator mass spectrometry have been concentrated in the earth sciences (climatology, cosmochemistry, environmental chemistry, geochronology, glaciology, hydrology, igneous petrogenesis, minerals exploration, sedimentology, and volcanology), in anthropology and archeology (radiocarbon dating), and in physics (searches for exotic particles and measurement of halflives). In addition, accelerator mass spectrometry may become an important tool for the materials and biological sciences.

  11. RADIOISOTOPE IDENTIFICATION OF SHIELDED AND MASKED SNM RDD MATERIALS

    SciTech Connect

    Salaymeh, S.; Jeffcoat, R.

    2010-06-17

    Sonar and speech techniques have been investigated to improve functionality and enable handheld and other man-portable, mobile, and portal systems to positively detect and identify illicit nuclear materials, with minimal data and with minimal false positives and false negatives. RadSonar isotope detection and identification is an algorithm development project funded by NA-22 and employing the resources of Savannah River National Laboratory and three University Laboratories (JHU-APL, UT-ARL, and UW-APL). Algorithms have been developed that improve the probability of detection and decrease the number of false positives and negatives. Two algorithms have been developed and tested. The first algorithm uses support vector machine (SVM) classifiers to determine the most prevalent nuclide(s) in a spectrum. It then uses a constrained weighted least squares fit to estimate and remove the contribution of these nuclide(s) to the spectrum, iterating classification and fitting until there is nothing of significance left. If any Special Nuclear Materials (SNMs) were detected in this process, a second tier of more stringent classifiers are used to make the final SNM alert decision. The second algorithm is looking at identifying existing feature sets that would be relevant in the radioisotope identification context. The underlying philosophy here is to identify parallels between the physics and/or the structures present in the data for the two applications (speech analysis and gamma spectroscopy). The expectation is that similar approaches may work in both cases. The mel-frequency cepstral representation of spectra is widely used in speech, particularly for two reasons: approximation of the response of the human ear, and simplicity of channel effect separation (in this context, a 'channel' is a method of signal transport that affects the signal, examples being vocal tract shape, room echoes, and microphone response). Measured and simulated gamma-ray spectra from a hand

  12. A power conditioning system for radioisotope thermoelectric generator energy sources

    NASA Technical Reports Server (NTRS)

    Gillis, J. A., Jr.

    1974-01-01

    The use of radioisotope thermoelectric generators (RTG) as the primary source of energy in unmanned spacecraft is discussed. RTG output control, power conditioning system requirements, the electrical design, and circuit performance are also discussed.

  13. Radioisotope Electric Propulsion (REP) for Selected Interplanetary Science Missions

    NASA Technical Reports Server (NTRS)

    Oh, David; Bonfiglio, Eugene; Cupples, Mike; Belcher, Jeremy; Witzberger, Kevin; Fiehler, Douglas; Artis, Gwen

    2005-01-01

    This viewgraph presentation analyzes small body targets (Trojan Asteroids), Medium Outer Planet Class (Jupiter Polar Orbiter with Probes), and Main Belt Asteroids and Comets (Comet Surface Sample Return), for Radioisotope Electric Propulsion (REP).

  14. Therapeutic clinical applications of reactor-produced radioisotopes

    SciTech Connect

    Knapp, F.F. Jr.

    1997-12-01

    One of the most rapidly growing areas of clinical nuclear medicine is the therapeutic use of radioisotopes for applications in oncology, rheumatology and, more recently, interventional cardiology. With the rapidly increasing development and evaluation of new agents, their introduction into clinical use, and commercialization, the availability of high levels of therapeutic reactor-produced neutron-rich radioisotopes is of increasing importance. The goals of this paper are to discuss the issues associated with optimization of the production and processing of reactor-produced radioisotopes for therapy, with special emphasis on {sup 188}W, and the optimization of the use of the {sup 188}W/{sup 188}Re generator. In addition, other key examples of therapeutic radioisotopes of current interest and their specific clinical applications are discussed.

  15. Thermal Model Predictions of Advanced Stirling Radioisotope Generator Performance

    NASA Technical Reports Server (NTRS)

    Wang, Xiao-Yen J.; Fabanich, William Anthony; Schmitz, Paul C.

    2014-01-01

    This presentation describes the capabilities of three-dimensional thermal power model of advanced stirling radioisotope generator (ASRG). The performance of the ASRG is presented for different scenario, such as Venus flyby with or without the auxiliary cooling system.

  16. Determining Molar Combining Ratios Using Radioisotopes--A Student Experiment

    ERIC Educational Resources Information Center

    Sears, Jerry A.

    1976-01-01

    Outlines an experimental procedure in which an iodine radioisotope is used to determine molar combining ratios of lead and silver with the iodine. Tables and graphs show the definitive results that should be attainable. (CP)

  17. Determining Molar Combining Ratios Using Radioisotopes--A Student Experiment

    ERIC Educational Resources Information Center

    Sears, Jerry A.

    1976-01-01

    Outlines an experimental procedure in which an iodine radioisotope is used to determine molar combining ratios of lead and silver with the iodine. Tables and graphs show the definitive results that should be attainable. (CP)

  18. Novel production techniques of radioisotopes using electron accelerators

    NASA Astrophysics Data System (ADS)

    Lowe, Daniel Robert

    Non-traditional radioisotope production techniques using a compact, high power linear electron accelerator have been demonstrated and characterized for the production of 18F, 47Sc, 147 Pm, and 99mTc from a variety of target candidates. These isotopes are used extensively in the medical field as diagnostic and therapy radioisotopes, as well as the space industry as RTG's. Primary focus was placed on 99mTc as it constitutes approximately 80% of all diagnostic procedures in the medical community that use radioactive tracers. It was also the prime focus due to recent events at the Chalk River nuclear reactor, which caused global shortages of this isotope a few years ago. A Varian K15 LINAC was first used to show proof of principle in Las Vegas. Various samples were then taken to the Idaho Accelerator Center where they were activated using an electron LINAC capable of electron energies from 4 to 25 MeV at a beam power of approximately 1 kW. Production rates, cross sections, and viability studies were then performed and conducted to assess the effectiveness of the candidate target and the maximum production rate for each radioisotope. Production rates for 18F from lithium fluoride salts were shown to be ideal at 21MeV, namely 1.7 Ci per kg of LiF salt, per kW of beam current, per 10 hour irradiation time. As the typical hospital consumption of 18F is around 500 mCi per day, it is clear that a large amount of 18F can be made from a small (300 gram) sample of LiF salt. However, since there is no current separation process for 18F from 19F, the viability of this technique is limited until a separations technique is developed. Furthermore, the calculated cross section for this reaction is in good agreement with literature, which supports the techniques for the isotopes mentioned below. Production rates for 47Sc from vanadium oxide targets were shown to be a maximum at 25 MeV with a production rate of 2 mCi per day, assuming a 2 kW beam and a 10 kg target. While this

  19. Some Characteristics of Radioisotope Power Sources in an Ocean Environment

    DTIC Science & Technology

    1974-03-01

    AD/A-002 129 SOME CHARACTERISTICS OF RADIOISOTOPE POWER SOURCES IN AN OCEAN ENVIRONMENT R. C. Erdmann, et al RAND Corporation S.,nta Monica...California March 1974 DISTRIBUTED BY: NItleId Tchinlald I ferrt Svice U. S. DEPARTMENT OF COMMERCE �.j I, ,- SOME CHARACTERISTICS OF RADIOISOTOPE POWER ... SOURCES IN AN OCEAN ENVIRONMENT R. C. ERDMAN3 E. C. GRITTON M. J. OZEROFF March 1974 -DDC, DEC 80 1974 L=-1 B P-5056-1 fotfotrduced by NATIONAL

  20. Efficiency of Pm-147 direct charge radioisotope battery.

    PubMed

    Kavetskiy, A; Yakubova, G; Yousaf, S M; Bower, K; Robertson, J D; Garnov, A

    2011-05-01

    A theoretical analysis is presented here of the efficiency of direct charge radioisotope batteries based on the efficiency of the radioactive source, the system geometry, electrostatic repulsion of beta particles from the collector, the secondary electron emission, and backscattered beta particles from the collector. Efficiency of various design batteries using Pm-147 sources was experimentally measured and found to be in good agreement with calculations. The present approach can be used for predicting the efficiency for different designs of direct charge radioisotope batteries.

  1. The Texas A&M Radioisotope Production and Radiochemistry Program

    SciTech Connect

    Akabani, Gamal

    2016-10-28

    The main motivation of the project at Texas A&M University was to carry out the production of critically needed radioisotopes used in medicine for diagnostics and therapy, and to establish an academic program in radionuclide production and separation methods. After a lengthy battle with the Texas A&M University Radiation Safety Office, the Texas Department of State Health Services granted us a license for the production of radionuclides in July 2015, allowing us to work in earnest in our project objectives. Experiments began immediately after licensing, and we started the assembly and testing of our target systems. There were four analytical/theoretical projects and two experimental target systems. These were for At-211 production and for Zn-62/Cu-62 production. The theoretical projects were related to the production of Mo-99/Tc-99m using a) a subcritical aqueous target system and b) production of Tc-99m from accelerator-generated Mo-99 utilizing a photon-neutron interaction with enriched Mo-100 targets. The two experimental projects were the development of targetry systems and production of At-211 and Zn-62/Cu-62 generator. The targetry system for At-211 has been tested and production of At-211 is chronic depending of availability of beam time at the cyclotron. The installation and testing of the targetry system for the production of Zn-62/Cu-62 has not been finalized. A description of the systems is described. The academic program in radionuclide production and separation methods was initiated in the fall of 2011 and, due to the lack of a radiochemistry laboratory, it was suspended. We expect to re-start the academic program at the Texas A&M Institute for Preclinical Studies under the Molecular Imaging Program.

  2. The Texas A&M Radioisotope Production and Radiochemistry Program

    SciTech Connect

    Akabani, Gamal

    2016-08-31

    The main motivation of the project at Texas A&M University was to carry out the production of critically needed radioisotopes used in medicine for diagnostic and therapy, and to establish an academic program in radionuclide production and separation methods. After a lengthy battle with the Texas A&M University Radiation Safety Office, the Texas Department of State Health Services granted us a license for the production of radionuclides in July 2015, allowing us to work in earnest in our project objectives. Experiments began immediately after licensing, and we started the assembly and testing of our target systems. There were four analytical/theoretical projects and two experimental target systems. These were for At-211 production and for Zn- 62/Cu-62 production. The theoretical projects were related to the production of Mo-99/Tc-99m using (a) a subcritical aqueous target system and (b) production of Tc-99m from accelerator-generated Mo-99 utilizing a photon-neutron interaction with enriched Mo-100 targets. The two experimental projects were the development of targetry systems and production of At-211 and Zn-62/Cu-62 generator. The targetry system for At-211 has been tested and production of At-211 is chronic depending of availability of beam time at the cyclotron. The installation and testing of the targetry system for the production of Zn-62/Cu-62 has not been finalized. A description of the systems is described. The academic program in radionuclide production and separation methods was initiated in the fall of 2011; due to the lack of a radiochemistry laboratory, it was suspended. We expect to re-start the academic program at the Texas A&M Institute for Preclinical Studies under the Molecular Imaging Program.

  3. Some geophysical considerations in radioisotope dating applications

    NASA Astrophysics Data System (ADS)

    Hayes, Robert

    2016-03-01

    Radioisotope dating only assumes radioactive decay laws are taking place allowing closed form solutions to be obtained in generating a sample date estimate. To be discussed in this work is the isotopic distribution expected in geological samples due to mass diffusion superimposed on that from simple radioactive decay. By taking into consideration the isotope effect (differential mass diffusion rates) when measuring isotopic ratios from very old samples, the distribution dependency will cause a bias if isotopic diffusion rates are not identical throughout a material (or at least across the boundaries of all samples measured). The isotope effect being that isotopes having a smaller atomic mass will diffuse faster in a medium than will their heavier counterparts causing concentration gradients of their ratios even when there are no contributions from radioactive decay which will tend to bias all sample ages (slopes of the isochron) to have a more linear distribution. The application to Sr/Rb dating is evaluated and shown to result in expected age overestimates. Suggested methods to test for this effect along with sample preparation techniques to minimize it are discussed. Special thanks the NCSU Nuclear Engineering Department.

  4. Reliability of Radioisotope Stirling Convertor Linear Alternator

    NASA Technical Reports Server (NTRS)

    Shah, Ashwin; Korovaichuk, Igor; Geng, Steven M.; Schreiber, Jeffrey G.

    2006-01-01

    Onboard radioisotope power systems being developed and planned for NASA s deep-space missions would require reliable design lifetimes of up to 14 years. Critical components and materials of Stirling convertors have been undergoing extensive testing and evaluation in support of a reliable performance for the specified life span. Of significant importance to the successful development of the Stirling convertor is the design of a lightweight and highly efficient linear alternator. Alternator performance could vary due to small deviations in the permanent magnet properties, operating temperature, and component geometries. Durability prediction and reliability of the alternator may be affected by these deviations from nominal design conditions. Therefore, it is important to evaluate the effect of these uncertainties in predicting the reliability of the linear alternator performance. This paper presents a study in which a reliability-based methodology is used to assess alternator performance. The response surface characterizing the induced open-circuit voltage performance is constructed using 3-D finite element magnetic analysis. Fast probability integration method is used to determine the probability of the desired performance and its sensitivity to the alternator design parameters.

  5. Radioisotopic heater units warm an interplanetary spacecraft

    SciTech Connect

    Franco-Ferreira, E.A.; Rinehart, G.H.

    1998-01-01

    The Cassini orbiter and Huygens probe, which were successfully launched on October 15, 1997, constitute NASA`s last grand-scale interplanetary mission of this century. The mission, which consists of a four-year, close-up study of Saturn and its moons, begins in July 2004 with Cassini`s 60 orbits of Saturn and about 33 fly-bys of the large moon Titan. The Huygens probe will descend and land on Titan. Investigations will include Saturn`s atmosphere, its rings and its magnetosphere. The atmosphere and surface of Titan and other icy moons also will be characterized. Because of the great distance of Saturn from the sun, some of the instruments and equipment on both the orbiter and the probe require external heaters to maintain their temperature within normal operating ranges. These requirements are met by Light Weight Radioisotope Heater Units (LWRHUs) designed, fabricated and safety tested at Los Alamos National Laboratory, New Mexico. An improved gas tungsten arc welding procedure lowered costs and decreased processing time for heat units for the Cassini spacecraft.

  6. Development of Water Target for Radioisotope Production

    NASA Astrophysics Data System (ADS)

    Tripp, Nathan

    2011-10-01

    Ongoing studies of plant physiology at TUNL require a supply of nitrogen-13 for use as a radiotracer. Production of nitrogen-13 using a water target and a proton beam follows the nuclear reaction 16-O(p,a)13-N. Unfortunately the irradiation of trace amounts of oxygen-18 within a natural water target produces fluorine-18 by the reaction 18-O(p, n)18-F. The presence of this second radioisotope reduces the efficacy of nitrogen-13 as a radiotracer. Designing a natural water target for nitrogen-13 production at TUNL required the design of several new systems to address the problems inherent in nitrogen-13 production. A heat exchanger cools the target water after irradiation within the target cell. The resulting improved thermal regulation of the target water prevents the system from overheating and minimizes the effect of the cavitations occurring within the target. Alumina pellets within a scrubbing unit remove the fluorine-18 contamination from the irradiated water. The modular design of the water target apparatus makes the system highly adaptable, allowing for easy reuse and adaptation of the different components into future projects. The newly designed and constructed water target should meet the current and future needs of TUNL researchers in the production of nitrogen-13. This TUNL REU project was funded in part by a grant from the National Science Foundation (NSF) NSF-PHY-08-51813.

  7. Light-weight radioisotope heater impact tests

    SciTech Connect

    Reimus, M.A.H.; Rinehart, G.H.; Herrera, A.

    1998-12-31

    The light-weight radioisotope heater unit (LWRHU) is a {sup 238}PuO{sub 2}-fueled heat source designed to provide one thermal watt in each of various locations on a spacecraft. Los Alamos National Laboratory designed, fabricated, and safety tested the LWRHU. The heat source consists of a hot-pressed {sup 238}PuO{sub 2} fuel pellet, a Pt-30Rh vented capsule, a pyrolytic graphite insulator, and a fineweave-pierced fabric graphite aeroshell assembly. To compare the performance of the LWRHUs fabricated for the Cassini mission with the performance of those fabricated for the Galileo mission, and to determine a failure threshold, two types of impact tests were conducted. A post-reentry impact test was performed on one of 180 flight-quality units produced for the Cassini mission and a series of sequential impact tests using simulant-fueled LWRHU capsules were conducted respectively. The results showed that deformation and fuel containment of the impacted Cassini LWRHU was similar to that of a previously tested Galileo LWRHU. Both units sustained minimal deformation of the aeroshell and fueled capsule; the fuel was entirely contained by the platinum capsule. Sequential impacting, in both end-on and side-on orientations, resulted in increased damage with each subsequent impact. Sequential impacting of the LWRHU appears to result in slightly greater damage than a single impact at the final impact velocity of 50 m/s.

  8. Reliability of Radioisotope Stirling Convertor Linear Alternator

    NASA Astrophysics Data System (ADS)

    Shah, Ashwin; Korovaichuk, Igor; Geng, Steven M.; Schreiber, Jeffrey G.

    2005-02-01

    Onboard radioisotope power systems being developed and planned for NASA's deep-space missions would require reliable design lifetimes of up to 14 yr. Critical components and materials of Stirling convertors have been undergoing extensive testing and evaluation in support of a reliable performance for the specified life span. Of significant importance to the successful development of the Stirling convertor is the design of a lightweight and highly efficient linear alternator. Alternator performance could vary due to small deviations in the permanent magnet properties, operating temperature, and component geometries. Durability prediction and reliability of the alternator may be affected by these deviations from nominal design conditions. Therefore, it is important to evaluate the effect of these uncertainties in predicting the reliability of the linear alternator performance. This paper presents a study in which a reliability-based methodology is used to assess alternator performance. The response surface characterizing the induced open-circuit voltage performance is constructed using 3-D finite element magnetic analysis. Fast probability integration method is used to determine the probability of the desired performance and its sensitivity to the alternator design parameters.

  9. Methods for producing Cu-67 radioisotope with use of a ceramic capsule for medical applications

    DOEpatents

    Ehst, David A.; Willit, James L.

    2016-04-12

    The present invention provides a method for producing Cu67 radioisotope suitable for use in medical applications. The method comprises irradiating a metallic zinc-68 (Zn68) target within a sealed ceramic capsule with a high energy gamma ray beam. After irradiation, the Cu67 is isolated from the Zn68 by any suitable method (e.g. chemical and or physical separation). In a preferred embodiment, the Cu67 is isolated by sublimation of the zinc in a ceramic sublimation tube to afford a copper residue containing Cu67. The Cu67 can be further purified by chemical means.

  10. Development of a radioisotope heat source for the two-watt radioisotope thermoelectric generator

    NASA Astrophysics Data System (ADS)

    Howell, Edwin I.; McNeil, Dennis C.; Amos, Wayne R.

    1992-01-01

    Described is a radioisotope heat source for the Two-Watt Radioisotope Thermoelectric Generator (RTG) which is being considered for possible application by the U.S. Navy and for other Department of Defense applications. The heat source thermal energy (75 Wt) is produced from the alpha decay of plutonium-238 which is in the form of high-fired plutonium dioxide. The capsule is non-vented and consists of three domed cylindrical components each closed with a corresponding sealed end cap. Surrounding the fuel is the liner component, which is fabricated from a tantalum-based alloy, T-111. Also fabricated from T-111 is the next component, the strength member, which serves to meet pressure and impact criteria. The outermost component, or clad, is the oxidation- and corrosion-resistant nickel-based alloy, Hastelloy S. This paper defines the design considerations, details the hardware fabrication and welding processes, discusses the addition of yttrium to the fuel to reduce liner embrittlement, and describes the testing that has been conducted or is planned to assure that there is fuel containment not only during the heat source operational life, but also in case of an accident environment.

  11. Light-Weight Radioisotope Heater Unit

    SciTech Connect

    Schock, Alfred

    1981-04-01

    DOE is developing a new generation of radioisotope-fueled 1-watt heaters, for initial use on NASA's upcoming Galileo and International Solar-Polar Missions. Each heater must contain passive safety provisions to ensure fuel retention under all credible accident conditions. Initial design reviews raised some concern about the accuracy of the predicted peak reenetry temperature, and about the adequacy of the safety margin under certain unlikely - but not impossible-reentry modes. Of particular concern was the possile release of the accumulated helium inventory from the fuel during the reentry heat pulse, and the potential effect of enhanced heat conduction due to helium buildup in gaps. The latter problem had not been addressed in previous studies. Fairchild carried out a large number of reentry thermal analyses to resolve the analytical uncertainties, and proposed design changes to reduce the thermal coupling between the aeroshell and the fuel capsule. For the computed reentry temperature history of the modified design, the rate of helium buildup in the gaps was analyzed. The analysis accounted for temperature-dependent helium diffusion through the fuel pellet and for leakage to space through the permeable aeroshell. It showed that most of the helium inventory leaves the fuel during reentry, but that it never reaches a continuum pressure in the gaps, and therefore has no significant thermal effect. Under these conditions, the Fairchild-modified design provides ample safety margin against clad failure, even for very unlikely reenty trajectories. The modified design was successfully vibration-tested and was subsequently adopted by the project. Cross Reference CID #8517. There are two copies in the file.

  12. Lightweight Radiators Being Developed or Advanced Stirling Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    Juhasz, Albert J.; Tew, Roy C.; Thieme, Lanny G.

    2001-01-01

    The thermodynamic heat-to-electric power conversion efficiency of Stirling systems is 3 to 5 times higher than that of thermoelectric converters. Hence for unmanned deep space probes, Stirling advanced radioisotope power systems (ARPS) could deliver up to 5 times as much power as radioisotope thermoelectric generators for the same amount of radioisotope, or they could require one-third to one-fifth as much isotope inventory for the same power output. However, Stirling power systems reject unconverted heat at much lower temperatures than radioisotope thermoelectric generators. Normally, this requires larger and heavier heat-rejection subsystems because of the greater radiator areas, which are proportional to the first power of the heat rejected and the fourth power of the absolute heat-rejection temperature, as specified by the Stefan-Boltzmann radiation heat transfer law. The development of directly coupled disk radiators using very high conductivity encapsulated thermopyrolitic graphite materials represents a significant advance in Stirling ARPS space heat-rejection subsystem technology. A conceptual Stirling ARPS with two engines coupled to a radioisotope general-purpose heat source (GPHS) is shown in the illustration.

  13. NASA's Advanced Radioisotope Power Conversion Technology Development Status

    NASA Technical Reports Server (NTRS)

    Anderson, David J.; Sankovic, John; Wilt, David; Abelson, Robert D.; Fleurial, Jean-Pierre

    2007-01-01

    NASA's Advanced Radioisotope Power Systems (ARPS) project is developing the next generation of radioisotope power conversion technologies that will enable future missions that have requirements that cannot be met by either photovoltaic systems or by current radioisotope power systems (RPSs). Requirements of advanced RPSs include high efficiency and high specific power (watts/kilogram) in order to meet future mission requirements with less radioisotope fuel and lower mass so that these systems can meet requirements for a variety of future space applications, including continual operation surface missions, outer-planetary missions, and solar probe. These advances would enable a factor of 2 to 4 decrease in the amount of fuel required to generate electrical power. Advanced RPS development goals also include long-life, reliability, and scalability. This paper provides an update on the contractual efforts under the Radioisotope Power Conversion Technology (RPCT) NASA Research Announcement (NRA) for research and development of Stirling, thermoelectric, and thermophotovoltaic power conversion technologies. The paper summarizes the current RPCT NRA efforts with a brief description of the effort, a status and/or summary of the contractor's key accomplishments, a discussion of upcoming plans, and a discussion of relevant system-level benefits and implications. The paper also provides a general discussion of the benefits from the development of these advanced power conversion technologies and the eventual payoffs to future missions (discussing system benefits due to overall improvements in efficiency, specific power, etc.).

  14. Daily intakes of naturally occurring radioisotopes in typical Korean foods.

    PubMed

    Choi, Min-Seok; Lin, Xiu-Jing; Lee, Sun Ah; Kim, Wan; Kang, Hee-Dong; Doh, Sih-Hong; Kim, Do-Sung; Lee, Dong-Myung

    2008-08-01

    The concentrations of naturally occurring radioisotopes ((232)Th, (228)Th, (230)Th, (228)Ra, (226)Ra, and (40)K) in typical Korean foods were evaluated. The daily intakes of these radioisotopes were calculated by comparing concentrations in typical Korean foods and the daily consumption rates of these foods. Daily intakes were as follows: (232)Th, 0.00-0.23; (228)Th, 0.00-2.04; (230)Th, 0.00-0.26; (228)Ra, 0.02-2.73; (226)Ra, 0.01-4.37 mBq/day; and (40)K, 0.01-5.71 Bq/day. The total daily intake of the naturally occurring radioisotopes measured in this study from food was 39.46 Bq/day. The total annual internal dose resulting from ingestion of radioisotopes in food was 109.83 muSv/y, and the radioisotope with the highest daily intake was (40)K. These values were same level compiled in other countries.

  15. NASA Radioisotope Power System Program - Technology and Flight Systems

    NASA Technical Reports Server (NTRS)

    Sutliff, Thomas J.; Dudzinski, Leonard A.

    2009-01-01

    NASA sometimes conducts robotic science missions to solar system destinations for which the most appropriate power source is derived from thermal-to-electrical energy conversion of nuclear decay of radioactive isotopes. Typically the use of a radioisotope power system (RPS) has been limited to medium and large-scale missions, with 26 U,S, missions having used radioisotope power since 1961. A research portfolio of ten selected technologies selected in 2003 has progressed to a point of maturity, such that one particular technology may he considered for future mission use: the Advanced Stirling Converter. The Advanced Stirling Radioisotope Generator is a new power system in development based on this Stirling cycle dynamic power conversion technology. This system may be made available for smaller, Discovery-class NASA science missions. To assess possible uses of this new capability, NASA solicited and funded nine study teams to investigate unique opportunities for exploration of potential destinations for small Discovery-class missions. The influence of the results of these studies and the ongoing development of the Advanced Stirling Radioisotope Generator system are discussed in the context of an integrated Radioisotope Power System program. Discussion of other and future technology investments and program opportunities are provided.

  16. High Efficiency Thermoelectric Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    El-Genk, Mohamed; Saber, Hamed; Caillat, Thierry

    2004-01-01

    The work performed and whose results presented in this report is a joint effort between the University of New Mexico s Institute for Space and Nuclear Power Studies (ISNPS) and the Jet Propulsion Laboratory (JPL), California Institute of Technology. In addition to the development, design, and fabrication of skutterudites and skutterudites-based segmented unicouples this effort included conducting performance tests of these unicouples for hundreds of hours to verify theoretical predictions of the conversion efficiency. The performance predictions of these unicouples are obtained using 1-D and 3-D models developed for that purpose and for estimating the actual performance and side heat losses in the tests conducted at ISNPS. In addition to the performance tests, the development of the 1-D and 3-D models and the development of Advanced Radioisotope Power systems for Beginning-Of-Life (BOM) power of 108 We are carried out at ISNPS. The materials synthesis and fabrication of the unicouples are carried out at JPL. The research conducted at ISNPS is documented in chapters 2-5 and that conducted at JP, in documented in chapter 5. An important consideration in the design and optimization of segmented thermoelectric unicouples (STUs) is determining the relative lengths, cross-section areas, and the interfacial temperatures of the segments of the different materials in the n- and p-legs. These variables are determined using a genetic algorithm (GA) in conjunction with one-dimensional analytical model of STUs that is developed in chapter 2. Results indicated that when optimized for maximum conversion efficiency, the interfacial temperatures between various segments in a STU are close to those at the intersections of the Figure-Of-Merit (FOM), ZT, curves of the thermoelectric materials of the adjacent segments. When optimizing the STUs for maximum electrical power density, however, the interfacial temperatures are different from those at the intersections of the ZT curves, but

  17. Hair radioactivity as a measure of exposure to radioisotopes

    NASA Technical Reports Server (NTRS)

    Strain, W. H.; Pories, W. J.; Fratianne, R. B.; Flynn, A.

    1972-01-01

    Since many radioisotopes accumulate in hair, this tropism was investigated by comparing the radioactivity of shaved with plucked hair collected from rats at various time intervals up to 24 hrs after intravenous injection of the ecologically important radioisotopes, iodine-131, manganese-54, strontium-85, and zinc-65. The plucked hair includes the hair follicles where biochemical transformations are taking place. The data indicate a slight surge of each radioisotpe into the hair immediately after injection, a variation of content of each radionuclide in the hair, and a greater accumulation of radioactivity in plucked than in shaved hair. These results have application not only to hair as a measure of exposure to radioisotopes, but also to tissue damage and repair at the hair follicle.

  18. Investigation of Miniaturized Radioisotope Thermionic Power Generation for General Use

    NASA Technical Reports Server (NTRS)

    Duzik, Adam J.; Choi, Sang H.

    2016-01-01

    Radioisotope thermoelectric generators (RTGs) running off the radioisotope Pu238 are the current standard in deep space probe power supplies. While reliable, these generators are very inefficient, operating at only approx.7% efficiency. As an alternative, more efficient radioisotope thermionic emission generators (RTIGs) are being explored. Like RTGs, current RTIGs concepts use exotic materials for the emitter, limiting applicability to space and other niche applications. The high demand for long-lasting mobile power sources would be satisfied if RTIGs could be produced inexpensively. This work focuses on exposing several common materials, such as Al, stainless steel, W, Si, and Cu, to elevated temperatures under vacuum to determine the efficiency of each material as inexpensive replacements for thermoelectric materials.

  19. Investigation of miniaturized radioisotope thermionic power generation for general use

    NASA Astrophysics Data System (ADS)

    Duzik, Adam J.; Choi, Sang H.

    2016-04-01

    Radioisotope thermoelectric generators (RTGs) running off the radioisotope Pu238 are the current standard in deep space probe power supplies. While reliable, these generators are very inefficient, operating at only ~7% efficiency. As an alternative, more efficient radioisotope thermionic emission generators (RTIGs) are being explored. Like RTGs, current RTIGs concepts use exotic materials for the emitter, limiting applicability to space and other niche applications. The high demand for long-lasting mobile power sources would be satisfied if RTIGs could be produced inexpensively. This work focuses on exposing several common materials, such as Al, stainless steel, W, Si, and Cu, to elevated temperatures under vacuum to determine the efficiency of each material as inexpensive replacements for thermoelectric materials.

  20. Realistic Specific Power Expectations for Advanced Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    Mason, Lee S.

    2006-01-01

    Radioisotope Power Systems (RPS) are being considered for a wide range of future NASA space science and exploration missions. Generally, RPS offer the advantages of high reliability, long life, and predictable power production regardless of operating environment. Previous RPS, in the form of Radioisotope Thermoelectric Generators (RTG), have been used successfully on many NASA missions including Apollo, Viking, Voyager, and Galileo. NASA is currently evaluating design options for the next generation of RPS. Of particular interest is the use of advanced, higher efficiency power conversion to replace the previous thermoelectric devices. Higher efficiency reduces the quantity of radioisotope fuel and potentially improves the RPS specific power (watts per kilogram). Power conversion options include Segmented Thermoelectric (STE), Stirling, Brayton, and Thermophotovoltaic (TPV). This paper offers an analysis of the advanced 100 watt-class RPS options and provides credible projections for specific power. Based on the analysis presented, RPS specific power values greater than 10 W/kg appear unlikely.

  1. A facility to remotely assemble radioisotope thermoelectric generators

    NASA Astrophysics Data System (ADS)

    Engstrom, John W.; Goldmann, Louis H.; Truitt, Ross W.

    1993-01-01

    Radioisotope Thermoelectric Generators (RTGs) are electrical power sources that use heat from decaying radioisotopes to directly generate electrical power. The RTG assembly process is performed in an inert atmosphere inside a large glovebox, which is surrounded by radiation shielding to reduce exposure to neutron and gamma radiation from the radioisotope heat source. In the past, allowable dose rate limits have allowed direct, manual assembly methods; however, current dose rate limits require a thicker radiation shielding that makes direct, manual assembly infeasible. To minimize RTG assembly process modifications, telerobotic systems are being investigated to perform remote assembly tasks. Telerobotic systems duplicate human arm motion and incorporate force feedback sensitivity to handle objects and tools in a human-like manner. A telerobotic system with two arms and a three-dimensional (3-D) vision system can be used to perform remote RTG assembly tasks inside gloveboxes and cells using unmodified, normal hand tools.

  2. Positive Influence of 177Lu PSMA-617 Therapy on Bone Marrow Depression Caused by Metastatic Prostate Cancer.

    PubMed

    Schlenkhoff, Carl Diedrich; Gaertner, Florian; Essler, Markus; Schmidt, Matthias; Ahmadzadehfar, Hojjat

    2016-06-01

    A 75-year-old man with castrate-resistant prostate cancer and increasing prostate-specific antigen (PSA) level developed severe bone marrow depression during Ra radionuclide therapy. Because of this, he was treated with Lu-PSMA in compassionate use for this not-yet-approved therapy. At the beginning of Lu-PSMA therapy, repeated blood transfusions (BT) were necessary. Six months after the last BT, after 3 cycles of Lu-PSMA, his blood count stabilized. He required no further BTs and his PSA level remained lowered.

  3. Successful Treatment of Hepatic Metastases of Hormone Refractory Prostate Cancer Using Radioligand Therapy With 177Lu-PSMA-617.

    PubMed

    Wei, Xiao; Schlenkhoff, Carl; Sopora, Claudia; Essler, Markus; Ahmadzadehfar, Hojjat

    2016-11-01

    An 81-year-old castrate-resistant prostate cancer man with multiple lymph node, bone, and hepatic metastases received four cycles of Lu-PSMA-617 treatments at our department from May to December 2015. All of his liver metastases showed PSMA expression in Ga-PSMA PET performed before the first cycle. Under this therapy, all of the metastases showed significant regression in size and PSMA expression over time.

  4. Peptide receptor radionuclide therapy with (177)Lu DOTATATE in a case of recurrent carotid body paraganglioma with spinal metastases.

    PubMed

    Gupta, Santosh Kumar; Singla, Suhas; Karunanithi, Sellam; Damle, Nishikant; Bal, Chandrasekhar

    2014-05-01

    Paragangliomas are rare benign neuroendocrine tumors, and 80% of all paragangliomas are either carotid body tumors or glomus jugulare tumors. We present a case of recurrent unresectable carotid body paraganglioma with nodal and T7 vertebral metastases in a 30-year-old man 6 years postsurgery detected with Ga DOTANOC PET/CT and was administered with peptide receptor radionuclide therapy using Lu DOTATATE. After 5 cycles of Lu DOTATATE (total cumulative activity of 750 mCi [27 GBq]), significant response at the primary site on Ga DOTANOC PET/CT and complete disappearance of nodal and T7 vertebral metastases were noted.

  5. Does the pretherapeutic tumor SUV in 68Ga DOTATOC PET predict the absorbed dose of 177Lu octreotate?

    PubMed

    Ezziddin, Samer; Lohmar, Jonas; Yong-Hing, Charlotte J; Sabet, Amir; Ahmadzadehfar, Hojjat; Kukuk, Guido; Biersack, Hans-Jürgen; Guhlke, Stefan; Reichmann, Karl

    2012-06-01

    Selection of candidates for peptide receptor radionuclide therapy (PRRT) is increasingly based on receptor positron emission tomography (PET) imaging, including the common tracer 68Ga DOTATOC. However, no studies have yet compared standardized uptake values (SUVs) and absorbed doses in this field. We retrospectively analyzed a consecutive cohort of 21 patients with 61 evaluable tumor lesions undergoing both pretherapeutic 68Ga DOTATOC-PET/CT (Biograph Duo [Siemens Medical Solutions, Erlangen, Germany]; PET acquisition, 75.3 ± 15.4 minutes postinjection; 117.3 ± 33.9 MBq 68Ga DOTATOC) and PRRT with Lu octreotate (7.47 ± 1.39 GBq; intratherapeutic tumor dosimetry with serial whole-body scans; 1, 2, and 4 days postinjection) at our institution. SUVs were compared with the tumor-absorbed doses per injected activity (D/A0) of the subsequent first treatment cycle. The correlation of SUV and D/A0 was r = 0.72 (SUVmean) and r = 0.71 (SUVmax), both P < 0.001. Pancreatic origin and hepatic localization were associated with higher D/A0, and chromogranin A level and Ki-67 index had no influence on SUV or D/A0. High-SUV lesions (SUVmean >15; SUVmax >25) resulted in high D/A0 (>10 Gy/GBq) in 66.7% to 70.8% and low D/A0 (<5 Gy/GBq) in only 8.3% to 12.5% on subsequent PRRT. The mentioned low D/A0 range, on the other hand, was achieved by all lesions with SUVmean <7 or SUVmax <9. Somatostatin receptor PET imaging may predict tumor-absorbed doses. The ability to indicate insufficient target irradiation by a low SUV could aid in selection of appropriate candidates for PRRT. However, larger series are needed to confirm and validate these initial findings.

  6. Skin dose saving of the staff in 90Y/177Lu peptide receptor radionuclide therapy with the automatic dose dispenser.

    PubMed

    Fioroni, Federica; Grassi, Elisa; Giorgia, Cavatorta; Sara, Rubagotti; Piccagli, Vando; Filice, Angelina; Mostacci, Domiziano; Versari, Annibale; Iori, Mauro

    2016-10-01

    When handling Y-labelled and Lu-labelled radiopharmaceuticals, skin exposure is mainly due to β-particles. This study aimed to investigate the equivalent dose saving of the staff when changing from an essentially manual radiolabelling procedure to an automatic dose dispenser (ADD). The chemist and physician were asked to wear thermoluminescence dosimeters on their fingertips to evaluate the quantity of Hp(0.07) on the skin. Data collected were divided into two groups: before introducing ADD (no ADD) and after introducing ADD. For the chemist, the mean values (95th percentile) of Hp(0.07) for no ADD and ADD are 0.030 (0.099) and 0.019 (0.076) mSv/GBq, respectively, for Y, and 0.022 (0.037) and 0.007 (0.023) mSv/GBq, respectively, for Lu. The reduction for ADD was significant (t-test with P<0.05) for both isotopes. The relative differences before and after ADD collected for every finger were treated using the Wilcoxon test, proving a significantly higher reduction in extremity dose to each fingertip for Lu than for Y (P<0.05). For the medical staff, the mean values of Hp(0.07) (95th percentile) for no ADD and ADD are 0.021 (0.0762) and 0.0143 (0.0565) mSv/GBq, respectively, for Y, and 0.0011 (0.00196) and 0.0009 (0.00263) mSv/GBq, respectively, for Lu. The t-test provided a P-value less than 0.05 for both isotopes, making the difference between ADD and no ADD significant. ADD positively affects the dose saving of the chemist in handling both isotopes. For the medical staff not directly involved with the introduction of the ADD system, the analysis shows a learning curve of the workers over a 5-year period. Specific devices and procedures allow staff skin dose to be limited.

  7. Procurement of a fully licensed radioisotope thermoelectric generator transportation system

    SciTech Connect

    Adkins, H.E.; Bearden, T.E.

    1990-10-01

    A fully licensed transportation system for Radioisotope Thermoelectric Generators and Light-Weight Radioisotope Heater Units is currently being designed and built. The system will comply with all applicable US Department of Transportation regulations without the use of a DOE Alternative.'' The US Department of Transportation has special double containment'' requirements for plutonium. The system packaging uses a doubly contained bell jar'' concept. A refrigerated trailer is used for cooling the high-heat payloads. The same packaging is used for both high- and low-heat payloads. The system is scheduled to be available for use by mid-1992. 4 refs., 4 figs., 2 tabs.

  8. Separation methods for high specific activity radioarsenic

    NASA Astrophysics Data System (ADS)

    Jurisson, S. S.; Wycoff, D. E.; DeGraffenreid, A.; Embree, M. F.; Ketring, A. R.; Cutler, C. S.; Fassbender, M. E.; Ballard, B.

    2012-12-01

    Radiopharmaceuticals require the use of high specific activity radionuclides, especially when targeting limited numbers of receptors on tumor surfaces. Two radioisotopes of arsenic (72As and 77As) are potentially useful in diagnostic and therapeutic radiopharmaceuticals. Methods for the production, separation, and isolation of high specific activity 72As and 77As are presented.

  9. Anthropogenic radioisotopes to estimate rates of soil redistribution by wind

    USDA-ARS?s Scientific Manuscript database

    Erosion of soil by wind and water is a degrading process that affects millions of hectares worldwide. Atmospheric testing of nuclear weapons and the resulting fallout of anthropogenic radioisotopes, particularly Cesium 137, has made possible the estimation of mean soil redistribution rates. The pe...

  10. Targets for the production of radioisotopes and method of assembly

    DOEpatents

    Quinby, Thomas C.

    1976-01-01

    A target for preparation of radioisotopes by nuclear bombardment, and a method for its assembly are provided. A metallic sample to be bombarded is enclosed within a metallic support structure and the resulting target subjected to heat and pressure to effect diffusion bonds therebetween. The bonded target is capable of withstanding prolonged exposure to nuclear bombardment without thermal damage to the sample.

  11. A Concept for a Radioisotope Powered Lunar CubeSat

    NASA Astrophysics Data System (ADS)

    Cataldo, R. L.

    2016-11-01

    Presented is a concept for a small lander or cubesat lunar mission that would benefit from a low-power milli-watt radioisotope power source (RPS). A RPS would provide long-lived electrical and thermal power enabling a long-lived lunar mission.

  12. Reentry thermal testing of light-weight radioisotope heater units

    SciTech Connect

    Peterson, D.E.; Starzynski, J.S.

    1982-03-01

    Two Light-Weight Radioisotope Heater Units (LWRHU) were exposed to thermal ramps simulating atmospheric reentry. The helium release rates were measured during each test and modeled after simple diffusion theory. The reentry pulses did not result in swelling of the claddings or degradation of fuel pellets.

  13. Radioisotope production and management at Oak Ridge National Laboratory

    SciTech Connect

    Collins, E.D.; Aaron, W.S.; Alexander, C.W.; Bigelow, J.E.; Parks, J.T.; Tracy, J.G.; Wham, R.M.

    1994-09-01

    The production of radioisotopes has been one of the basic activities at Oak Ridge since the end of World War II. The importance of this work was best described by Alvin Weinberg, former Laboratory Director, when he wrote ``... If God has a golden book and writes down what it is that Oak Ridge National Laboratory did that had the biggest influence on science, I would guess that was the production and distribution of isotopes.`` Radioisotopes production continues to be an important aspect of Oak Ridge programs today and of those planned for the future. Past activities, current projects, and future plans and potentials will be described briefly in this paper. Also, some of the major issues facing the continued production of radioisotopes will be described. The scope of the program has always been primarily that of process development, followed by special batch-type productions, where no other supply exists. The technology developed has been available for adoption by US commercial corporations, and in cases where this has occurred, Oak Ridge has withdrawn as a supplier of the particular isotopes involved. One method of production that will not be described is that of target bombardment with an accelerator. This method was used at Oak Ridge prior to 1978 in the 86-inch Cyclotron. However, this method has not been used at Oak Ridge since then for radioisotope production, except as a research tool.

  14. Radioisotope research, production, and processing at the University of Missouri Research Reactor

    SciTech Connect

    Ehrhardt, G.J.; Ketring, A.R.; Ja, Wei; Ma, D.; Zinn, K.; Lanigan, J.

    1995-12-31

    The University of Missouri Research Reactor (MURR) is a 10 MW, light-water-cooled and moderated research reactor which first achieved criticality in 1996 and is currently the highest powered university-owned research reactor in the U.S. For many years a major supplier of reactor-produced isotopes for research and commercial purposes, in the last 15 years MURR has concentrated on development of reactor-produced beta-particle emitters for experimental use in nuclear medicine therapy of cancer and rheumatoid arthritis. MURR has played a major role in the development of bone cancer pain palliation with the agents {sup 153}Sm EDTMP and {sup 186}Re/{sup 188}Re HEDP, as well as in the use of {sup 186}Re, {sup 177}Lu, {sup 166}Ho, and {sup 105}Rh for radioimmunotherapy and receptor-agent-guided radiotherapy. MURR is also responsible for the development of therapeutic, {sup 90}Y-labeled glass microspheres for the treatment of liver tumors, a product ({sup 90}Y Therasphere{trademark}) which is currently an approved drug in Canada. MURR has also pioneered the development of {sup 188}W/{sup 188}Re and {sup 99}Mo/{sup 99m}Tc gel generators, which make the use of low specific activity {sup 188}W and {sup 99}Mo practical for such isotope generators.

  15. Production capabilities in US nuclear reactors for medical radioisotopes

    SciTech Connect

    Mirzadeh, S.; Callahan, A.P.; Knapp, F.F. Jr. ); Schenter, R.E. )

    1992-11-01

    The availability of reactor-produced radioisotopes in the United States for use in medical research and nuclear medicine has traditionally depended on facilities which are an integral part of the US national laboratories and a few reactors at universities. One exception is the reactor in Sterling Forest, New York, originally operated as part of the Cintichem (Union Carbide) system, which is currently in the process of permanent shutdown. Since there are no industry-run reactors in the US, the national laboratories and universities thus play a critical role in providing reactor-produced radioisotopes for medical research and clinical use. The goal of this survey is to provide a comprehensive summary of these production capabilities. With the temporary shutdown of the Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR) in November 1986, the radioisotopes required for DOE-supported radionuclide generators were made available at the Brookhaven National Laboratory (BNL) High Flux Beam Reactor (HFBR). In March 1988, however, the HFBR was temporarily shut down which forced investigators to look at other reactors for production of the radioisotopes. During this period the Missouri University Research Reactor (MURR) played an important role in providing these services. The HFIR resumed routine operation in July 1990 at 85 MW power, and the HFBR resumed operation in June 1991, at 30 MW power. At the time of the HFBR shutdown, there was no available comprehensive overview which could provide information on status of the reactors operating in the US and their capabilities for radioisotope production. The obvious need for a useful overview was thus the impetus for preparing this survey, which would provide an up-to-date summary of those reactors available in the US at both the DOE-funded national laboratories and at US universities where service irradiations are currently or expected to be conducted.

  16. Production capabilities in US nuclear reactors for medical radioisotopes

    SciTech Connect

    Mirzadeh, S.; Callahan, A.P.; Knapp, F.F. Jr.; Schenter, R.E.

    1992-11-01

    The availability of reactor-produced radioisotopes in the United States for use in medical research and nuclear medicine has traditionally depended on facilities which are an integral part of the US national laboratories and a few reactors at universities. One exception is the reactor in Sterling Forest, New York, originally operated as part of the Cintichem (Union Carbide) system, which is currently in the process of permanent shutdown. Since there are no industry-run reactors in the US, the national laboratories and universities thus play a critical role in providing reactor-produced radioisotopes for medical research and clinical use. The goal of this survey is to provide a comprehensive summary of these production capabilities. With the temporary shutdown of the Oak Ridge National Laboratory (ORNL) High Flux Isotope Reactor (HFIR) in November 1986, the radioisotopes required for DOE-supported radionuclide generators were made available at the Brookhaven National Laboratory (BNL) High Flux Beam Reactor (HFBR). In March 1988, however, the HFBR was temporarily shut down which forced investigators to look at other reactors for production of the radioisotopes. During this period the Missouri University Research Reactor (MURR) played an important role in providing these services. The HFIR resumed routine operation in July 1990 at 85 MW power, and the HFBR resumed operation in June 1991, at 30 MW power. At the time of the HFBR shutdown, there was no available comprehensive overview which could provide information on status of the reactors operating in the US and their capabilities for radioisotope production. The obvious need for a useful overview was thus the impetus for preparing this survey, which would provide an up-to-date summary of those reactors available in the US at both the DOE-funded national laboratories and at US universities where service irradiations are currently or expected to be conducted.

  17. Preparing for Harvesting Radioisotopes from FRIB

    SciTech Connect

    Lapi, Suzanne

    2015-11-30

    In the second quarter of this grant, work has progressed smoothly at all three collaborating institutions. We have recently completed our first experiment at the NSCL under this grant successfully, where 79Kr was collected by cryotrapping from our water target apparatus. The three PI’s, one undergraduate (Boone Marois), two graduate students (Stacy Queern and Matt Scott) and one post-doc (Aranh Pen) were assisted by Dave Morrissey at the NSCL to perform this experiment. The experiment also provided the opportunity for a collaboration meeting of the PI’s to discuss future work on this proposal. Significant progress has been made on both novel radiochemical separations technology at the University of Missouri, and validating a radiochemical separation procedure for 48V at Washington University. The only change in the work-scope of the original proposal is the transition of the Washington University PI to the University of Alabama at Birmingham.

  18. Iotron development of Cu67 radioisotope

    SciTech Connect

    Ehst, David A.

    2016-10-31

    The collaboration has developed a method of producing the Cu-67 medical isotope for beta therapy of cancers such as non-Hodgkins melanoma. In particular we have used electron linac production of intense gamma ray beams to convert Zn-68 into Cu-67 in metal targets. The targets are subsequently processed by separating the Cu isotope from the Zn metal using sublimation, with ceramic components to avoid contamination of the final product.

  19. Reactor production and processing of radioisotopes for therapeutic applications in nuclear medicine

    SciTech Connect

    Knapp, F.F. Jr.; Mirzadeh, S.; Beets, A.L.

    1995-02-01

    Nuclear reactors continue to play an important role in providing radioisotopes for nuclear medicine. Many reactor-produced radioisotopes are ``neutron rich`` and decay by beta-emission and are thus of interest for therapeutic applications. This talk discusses the production and processing of a variety of reactor-produced radioisotopes of current interest, including those produced by the single neutron capture process, double neutron capture and those available from beta-decay of reactorproduced radioisotopes. Generators prepared from reactorproduced radioisotopes are of particular interest since repeated elution inexpensively provides many patient doses. The development of the alumina-based W-188/Re-188 generator system is discussed in detail.

  20. Berkeley Off-line Radioisotope Generator (BORG)

    SciTech Connect

    Sudowe, Ralf; Patin, Joshua B.

    2001-07-23

    Development of chemical separations for the transactinides has traditionally been performed with longer-lived tracer activities purchased commercially. With these long-lived tracers, there is always the potential problem that the tracer atoms are not always in the same chemical form as the short-lived atoms produced in on-line experiments. This problem is especially severe for elements in groups 4 and 5 of the periodic table, where hydrolysis is present. The long-lived tracers usually are stored with a complexing agent to prevent sorption or precipitation. Chemistry experiments performed with these long-lived tracers are therefore not analogous to those chemical experiments performed in on-line experiments. One way to eliminate the differences between off-line and on-line chemistry experiments is through the use of a {sup 252}Cf fission fragment collection device. A {sup 252}Cf fission fragment collection device has already been constructed [1]. This device is limited in its capabilities. A new fission fragment device would allow the study of the chemical properties of the homologues of the heaviest elements. This new device would be capable of producing fission fragments for fast gas chemistry and aqueous chemistry experiments, long-lived tracers for model system development and neutrons for neutron activation. Fission fragment activities produced in this way should have the same chemical form as those produced in Cyclotron irradiations. The simple operation of this source will allow more rapid and reliable development of radiochemical separations with homologues of transactinide elements.

  1. Methods for separating medical isotopes using ionic liquids

    DOEpatents

    Luo, Huimin; Boll, Rose Ann; Bell, Jason Richard; Dai, Sheng

    2014-10-21

    A method for extracting a radioisotope from an aqueous solution, the method comprising: a) intimately mixing a non-chelating ionic liquid with the aqueous solution to transfer at least a portion of said radioisotope to said non-chelating ionic liquid; and b) separating the non-chelating ionic liquid from the aqueous solution. In preferred embodiments, the method achieves an extraction efficiency of at least 80%, or a separation factor of at least 1.times.10.sup.4 when more than one radioisotope is included in the aqueous solution. In particular embodiments, the method is applied to the separation of medical isotopes pairs, such as Th from Ac (Th-229/Ac-225, Ac-227/Th-227), or Ra from Ac (Ac-225 and Ra-225, Ac-227 and Ra-223), or Ra from Th (Th-227 and Ra-223, Th-229 and Ra-225).

  2. Multipurpose insulation system for a radioisotope fueled Mini-Brayton Heat Source Assembly

    NASA Technical Reports Server (NTRS)

    Aller, P.; Saylor, W.; Schmidt, G.; Wein, D.

    1976-01-01

    The Mini-Brayton Heat Source Assembly (HSA) consists of a radioisotope fueled heat source, a heat exchanger, a multifoil thermal insulation blanket, and a hermetically sealed housing. The thermal insulation blanket is a multilayer wrap of thin metal foil separated by a sparsely coated oxide. The objectives of the insulation blanket are related to the effective insulation of the HSA during operation, the transfer of the full thermal inventory to the housing when the primary coolant is not flowing, and the transfer of the full thermal inventory to the housing in the event of a flow stoppage of the primary coolant. A description is given of the approaches which have been developed to make it possible for the insulation blanket to meet these requirements.

  3. Investigation of Insulation Materials for Future Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    Cornell, Peggy A.; Hurwitz, Frances I.; Ellis, David L.; Schmitz, Paul C.

    2013-01-01

    NASA's Radioisotope Power Systems (RPS) Technology Advancement Project is developing next generation high-temperature insulation materials that directly benefit thermal management and improve performance of RPS for future science missions. Preliminary studies on the use of multilayer insulation (MLI) for Stirling convertors used on the Advanced Stirling Radioisotope Generator (ASRG) have shown the potential benefits of MLI for space vacuum applications in reducing generator size and increasing specific power (W/kg) as compared to the baseline Microtherm HT (Microtherm, Inc.) insulation. Further studies are currently being conducted at NASA Glenn Research Center on candidate MLI foils and aerogel composite spacers. This paper presents the method of testing of foils and spacers and experimental results to date.

  4. Investigation of Insulation Materials for Future Radioisotope Power Systems (RPS)

    NASA Technical Reports Server (NTRS)

    Cornell, Peggy A.; Hurwitz, Frances I.; Ellis, David L.; Schmitz, Paul C.

    2013-01-01

    NASA's Radioisotope Power System (RPS) Technology Advancement Project is developing next generation high temperature insulation materials that directly benefit thermal management and improve performance of RPS for future science missions. Preliminary studies on the use of multilayer insulation (MLI) for Stirling convertors used on the Advanced Stirling Radioisotope Generator (ASRG) have shown the potential benefits of MLI for space vacuum applications in reducing generator size and increasing specific power (W/kg) as compared to the baseline Microtherm HT (Microtherm, Inc.) insulation. Further studies are currently being conducted at NASA Glenn Research Center (GRC) on candidate MLI foils and aerogel composite spacers. This paper presents the method of testing of foils and spacers and experimental results to date.

  5. Emitted radiation characteristics of plutonium dioxide radioisotope thermoelectric generators

    NASA Technical Reports Server (NTRS)

    Gingo, P. J.; Steyn, J. J.

    1971-01-01

    The nuclear and emitted radiation characteristics of the radioisotope elements and impurities in commercial grade plutonium dioxide are presented in detail. The development of the methods of analysis are presented. Radioisotope thermoelectric generators (RTG) of 1575, 3468 and 5679 thermal watts are characterized with respect to neutron and gamma photon source strength as well as spatial and number flux distribution. The results are presented as a function of detector position and light element contamination concentration for fuel age ranging from 'fresh' to 18 years. The data may be used to obtain results for given O-18 and Pu-236 concentrations. The neutron and gamma photon flux and dose calculations compare favorably with reported experimental values for SNAP-27.

  6. Radioisotope Electric Propulsion for Fast Outer Planetary Orbiters

    NASA Technical Reports Server (NTRS)

    Oleson, Steven; Benson, Scott; Gefert, Leon; Patterson, Michael; Schreiber, Jeffrey

    2002-01-01

    Recent interest in outer planetary targets by the Office of Space Science has spurred the search for technology options to enable relatively quick missions to outer planetary targets. Several options are being explored including solar electric propelled stages combined with aerocapture at the target and nuclear electric propulsion. Another option uses radioisotope powered electric thrusters to reach the outer planets. Past work looked at using this technology to provide faster flybys. A better use for this technology is for outer planet orbiters. Combined with medium class launch vehicles and a new direct trajectory these small, sub-kilowatt ion thrusters and Stirling radioisotope generators were found to allow missions as fast as 5 to 12 years for objects from Saturn to Pluto, respectively. Key to the development is light spacecraft and science payload technologies.

  7. Outer Planet Exploration with Advanced Radioisotope Electric Propulsion

    NASA Technical Reports Server (NTRS)

    Oleson, Steven; Gefert, Leon; Patterson, Michael; Schreiber, Jeffrey; Benson, Scott; McAdams, Jim; Ostdiek, Paul

    2002-01-01

    In response to a request by the NASA Deep Space Exploration Technology Program, NASA Glenn Research Center conducted a study to identify advanced technology options to perform a Pluto/Kuiper mission without depending on a 2004 Jupiter Gravity Assist, but still arriving before 2020. A concept using a direct trajectory with small, sub-kilowatt ion thrusters and Stirling radioisotope power systems was shown to allow the same or smaller launch vehicle class as the chemical 2004 baseline and allow a launch slip and still flyby in the 2014 to 2020 timeframe. With this promising result the study was expanded to use a radioisotope power source for small electrically propelled orbiter spacecraft for outer planet targets such as Uranus, Neptune, and Pluto.

  8. Detectors for medical radioisotope imaging: demands and perspectives

    NASA Astrophysics Data System (ADS)

    Lopes, M. I.; Chepel, V.

    2004-10-01

    Radioisotope imaging is used to obtain information on biochemical processes in living organisms, being a tool of increasing importance for medical diagnosis. The improvement and expansion of these techniques depend on the progress attained in several areas, such as radionuclide production, radiopharmaceuticals, radiation detectors and image reconstruction algorithms. This review paper will be concerned only with the detector technology. We will review in general terms the present status of medical radioisotope imaging instrumentation with the emphasis put on the developments of high-resolution gamma cameras and PET detector systems for scinti-mammography and animal imaging. The present trend to combine two or more modalities in a single machine in order to obtain complementary information will also be considered.

  9. Environmental assessment for radioisotope heat source fuel processing and fabrication

    SciTech Connect

    Not Available

    1991-07-01

    DOE has prepared an Environmental Assessment (EA) for radioisotope heat source fuel processing and fabrication involving existing facilities at the Savannah River Site (SRS) near Aiken, South Carolina and the Los Alamos National Laboratory (LANL) near Los Alamos, New Mexico. The proposed action is needed to provide Radioisotope Thermoelectric Generators (RTG) to support the National Aeronautics and Space Administration's (NASA) CRAF and Cassini Missions. Based on the analysis in the EA, DOE has determined that the proposed action does not constitute a major Federal action significantly affecting the quality of the human environment within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, an Environmental Impact Statement is not required. 30 refs., 5 figs.

  10. Metal matrix composite fuel for space radioisotope energy sources

    NASA Astrophysics Data System (ADS)

    Williams, H. R.; Ning, H.; Reece, M. J.; Ambrosi, R. M.; Bannister, N. P.; Stephenson, K.

    2013-02-01

    Radioisotope fuels produce heat that can be used for spacecraft thermal control or converted to electricity. They must retain integrity in the event of destruction or atmospheric entry of the parent spacecraft. Addition of a metal matrix to the actinide oxide could yield a more robust fuel form. Neodymium (III) oxide (Nd2O3) - niobium metal matrix composites were produced using Spark Plasma Sintering; Nd2O3 is a non-radioactive surrogate for americium (III) oxide (Am2O3). Two compositions, 70 and 50 wt% Nd2O3, were mechanically tested under equibiaxial (ring-on-ring) flexure according to ASTM C1499. The addition of the niobium matrix increased the mean flexural strength by a factor of about 2 compared to typical ceramic nuclear fuels, and significantly increased the Weibull modulus to over 20. These improved mechanical properties could result in reduced fuel dispersion in severe accidents and improved safety of space radioisotope power systems.

  11. Safety status of space radioisotope and reactor power sources

    NASA Technical Reports Server (NTRS)

    Bennett, Gary L.

    1990-01-01

    The current overall safety criterion for both radioisotope and reactor power sources is containment or immobilization in the case of a reentry accident. In addition, reactors are designed to remain subcritical under conditions of land impact or water immersion. A very extensive safety test and analysis program was completed on the radioisotope thermoelectric generators (RTGs) in use on the Galileo spacecraft and planned for use on the Ulysses spacecraft. The results of this work show that the RTGs will pose little or no risk for any credible accident. The SP-100 space nuclear reactor program has begun addressing its safety criteria, and the design is planned to be such as to ensure meeting the various safety criteria. Preliminary mission risk analyses on SP-100 show the expected value population dose from postulated accidents on the reference mission to be very small. It is concluded that the current US nuclear power sources are the safest flown.

  12. A radioisotope-powered surface acoustic wave transponder

    NASA Astrophysics Data System (ADS)

    Tin, S.; Lal, A.

    2009-09-01

    We demonstrate a 63Ni radioisotope-powered pulse transponder that has a SAW (surface acoustic wave) device as the frequency transmission frequency selector. Because the frequency is determined by a SAW device, narrowband detection with an identical SAW device enables the possibility for a long-distance RF-link. The SAW transponders can be buried deep into structural constructs such as steel and concrete, where changing batteries or harvesting vibration or EM energy is not a reliable option. RF-released power to radioisotope- released power amplification is 108, even when regulatory safe amounts of 63Ni are used. Here we have achieved an 800 µW pulse (315 MHz, 10 µs pause) across a 50 Ω load every 3 min, using a 1.5 milli-Ci 63Ni source.

  13. Plastic Gamma Sensors: An Application in Detection of Radioisotopes

    SciTech Connect

    S. Mukhopadhyay

    2003-06-01

    A brief survey of plastic scintillators for various radiation measurement applications is presented here. The utility of plastic scintillators for practical applications such as gamma radiation monitoring, real-time radioisotope detection and screening is evaluated in laboratory and field measurements. This study also reports results of Monte Carlo-type predictive responses of common plastic scintillators in gamma and neutron radiation fields. Small-size plastic detectors are evaluated for static and dynamic gamma-ray detection sensitivity of selected radiation sources.

  14. Radioisotope powered alkali metal thermoelectric converter design for space systems

    NASA Technical Reports Server (NTRS)

    Sievers, R. K.; Bankston, C. P.

    1988-01-01

    The design concept of an alkali-metal thermoelectric converter (AMTEC) for 15-30-percent-efficient conversion of heat from the General Purpose (radioisotope) Heat Source (GPHS) on spacecraft is presented. The basic physical principles of the conversion cycle are outlined; a theoretical model is derived; a modular design is described and illustrated with drawings; and the overall AMTEC/GPHS system design is characterized. Predicted performance data are presented in extensive tables and graphs and discussed in detail.

  15. Radioisotope thermoelectric generator transportation system subsystem 143 software development plan

    SciTech Connect

    King, D.A.

    1994-11-10

    This plan describes the activities to be performed and the controls to be applied to the process of specifying, developing, and qualifying the data acquisition software for the Radioisotope Thermoelectric Generator (RTG) Transportation System Subsystem 143 Instrumentation and Data Acquisition System (IDAS). This plan will serve as a software quality assurance plan, a verification and validation (V and V) plan, and a configuration management plan.

  16. Radioisotope thermoelectric generator transportation system subsystem 143 software development plan

    NASA Astrophysics Data System (ADS)

    King, D. A.

    1994-11-01

    This plan describes the activities to be performed and the controls to be applied to the process of specifying, developing, and qualifying the data acquisition software for the Radioisotope Thermoelectric Generator (RTG) Transportation System Subsystem 143 Instrumentation and Data Acquisition System (IDAS). This plan will serve as a software quality assurance plan, a verification and validation (V and V) plan, and a configuration management plan.

  17. Radioisotope thermoelectric generator licensed hardware package and certification tests

    NASA Astrophysics Data System (ADS)

    Goldmann, L. H.; Averette, H. S.

    1994-09-01

    This paper presents the Licensed Hardware package and the Certification Test portions of the Radioisotope Thermoelectric Generator Transportation System. This package has been designed to meet those portions of the Code of Federal Regulations (10 CFR 71) relating to 'Type B' shipments of radioactive materials. The detailed information for the anticipated license is presented in the safety analysis report for packaging, which is now in process and undergoing necessary reviews. As part of the licensing process, a full-size Certification Test Article unit, which has modifications slightly different than the Licensed Hardware or production shipping units, is used for testing. Dimensional checks of the Certification Test Article were made at the manufacturing facility. Leak testing and drop testing were done at the 300 Area of the US Department of Energy's Hanford Site near Richland, Washington. The hardware includes independent double containments to prevent the environmental spread of Pu-238, impact limiting devices to protect portions of the package from impacts, and thermal insulation to protect the seal areas from excess heat during accident conditions. The package also features electronic feed-throughs to monitor the Radioisotope Thermoelectric Generator's temperature inside the containment during the shipment cycle. This package is designed to safely dissipate the typical 4500 thermal watts produced in the largest Radioisotope Thermoelectric Generators. The package also contains provisions to ensure leak tightness when radioactive materials, such as a Radioisotope Thermoelectric Generator for the Cassini Mission, planned for 1997 by the National Aeronautics and Space Administration, are being prepared for shipment. These provisions include test ports used in conjunction with helium mass spectrometers to determine seal leakage rates of each containment during the assembly process.

  18. Radioisotope Concentration in Lake Sediments of Maracaibo, Venezuela

    SciTech Connect

    Salas, A. Rangel; Viloria, T.; Sajo-Bohus, L.; Barros, H.; Greaves, E. D.; Palacios, D.

    2007-10-26

    Maracaibo Lake is one of the most important water basing and oil producing regions in Venezuela. Changes in the local environment have been monitored for chemical pollution in the past. For this study we selected a set of sediment samples collected in the shore and analyzed for its radioisotope content. Results show the gamma emitting isotopes distribution. Isotopes concentrations have been determined within the natural K, Th and U families.

  19. Development of an Integrated Robotic Radioisotope Identification and Location System

    DTIC Science & Technology

    2009-05-05

    468 Radium - 226 Ra226 1 1600 186 Radioactive waste from nuclear power plants and dismantled weapons sound like tempting targets for a terrorist to...system within a robotic base in order to inspect an area for either radioisotopes that could be used for a radiological dispersal device (RDD) or are... used for a radiological dispersal device (RDD) or are classified as Special Nuclear Material (SNM). In the current security climate, such a

  20. Isotope Identification in the GammaTracker Handheld Radioisotope Identifier

    SciTech Connect

    Batdorf, Michael T.; Hensley, Walter K.; Seifert, Carolyn E.; Kirihara, Leslie J.; Erikson, Luke E.; Jordan, David V.

    2009-11-13

    GammaTracker is a portable handheld radioisotope identifier using position sensitive CdZnTe crystals. The device uses a peak-based method for isotope identification implemented on an embedded computing platform within the device. This paper presents the run-time optimized algorithms used in this peak-based approach. Performance of the algorithms is presented using measured data from gamma-ray sources.

  1. Radioisotope Power: A Key Technology for Deep Space Explorations

    NASA Technical Reports Server (NTRS)

    Schmidt, George R.; Sutliff, Thomas J.; Duddzinski, Leonard

    2009-01-01

    A Radioisotope Power System (RPS) generates power by converting the heat released from the nuclear decay of radioactive isotopes, such as Plutonium-238 (Pu-238), into electricity. First used in space by the U.S. in 1961, these devices have enabled some of the most challenging and exciting space missions in history, including the Pioneer and Voyager probes to the outer solar system; the Apollo lunar surface experiments; the Viking landers; the Ulysses polar orbital mission about the Sun; the Galileo mission to Jupiter; the Cassini mission orbiting Saturn; and the recently launched New Horizons mission to Pluto. Radioisotopes have also served as a versatile heat source for moderating equipment thermal environments on these and many other missions, including the Mars exploration rovers, Spirit and Opportunity. The key advantage of RPS is its ability to operate continuously, independent of orientation and distance relative to the Sun. Radioisotope systems are long-lived, rugged, compact, highly reliable, and relatively insensitive to radiation and other environmental effects. As such, they are ideally suited for missions involving long-lived, autonomous operations in the extreme conditions of space and other planetary bodies. This paper reviews the history of RPS for the U.S. space program. It also describes current development of a new Stirling cycle-based generator that will greatly expand the application of nuclear-powered missions in the future.

  2. NASA's Radioisotope Power Systems Planning and Potential Future Systems Overview

    NASA Technical Reports Server (NTRS)

    Zakrajsek, June F.; Woerner, Dave F.; Cairns-Gallimore, Dirk; Johnson, Stephen G.; Qualls, Louis

    2016-01-01

    The goal of NASA's Radioisotope Power Systems (RPS) Program is to make RPS ready and available to support the exploration of the solar system in environments where the use of conventional solar or chemical power generation is impractical or impossible to meet the needs of the missions. To meet this goal, the RPS Program, working closely with the Department of Energy, performs mission and system studies (such as the recently released Nuclear Power Assessment Study), assesses the readiness of promising technologies to infuse in future generators, assesses the sustainment of key RPS capabilities and knowledge, forecasts and tracks the Program's budgetary needs, and disseminates current information about RPS to the community of potential users. This process has been refined and used to determine the current content of the RPS Program's portfolio. This portfolio currently includes an effort to mature advanced thermoelectric technology for possible integration into an enhanced Multi-Mission Radioisotope Generator (eMMRTG), sustainment and production of the currently deployed MMRTG, and technology investments that could lead to a future Stirling Radioisotope Generator (SRG). This paper describes the program planning processes that have been used, the currently available MMRTG, and one of the potential future systems, the eMMRTG.

  3. Stimulus sensitive gel with radioisotope and methods of making

    DOEpatents

    Weller, Richard E.; Lind, Michael A.; Fisher, Darrell R.; Gutowska, Anna; Campbell, Allison A.

    2005-03-22

    The present invention is a thermally reversible stimulus-sensitive gel or gelling copolymer radioisotope carrier that is a linear random copolymer of an [meth-]acrylamide derivative and a hydrophilic comonomer, wherein the linear random copolymer is in the form of a plurality of linear chains having a plurality of molecular weights greater than or equal to a minimum gelling molecular weight cutoff. Addition of a biodegradable backbone and/or a therapeutic agent imparts further utility. The method of the present invention for making a thermally reversible stimulus-sensitive gelling copolymer radionuclcide carrier has the steps of: (a) mixing a stimulus-sensitive reversible gelling copolymer with an aqueous solvent as a stimulus-sensitive reversible gelling solution; and (b) mixing a radioisotope with said stimulus-sensitive reversible gelling solution as said radioisotope carrier. The gel is enhanced by either combining it with a biodegradable backbone and/or a therapeutic agent in a gelling solution made by mixing the copolymer with an aqueous solvent.

  4. Stimulus sensitive gel with radioisotope and methods of making

    DOEpatents

    Weller, Richard E [Selah, WA; Lind, Michael A [Kent, WA; Fisher, Darrell R [Richland, WA; Gutowska, Anna [Richland, WA; Campbell, Allison A [Kennewick, WA

    2001-10-02

    The present invention is a thermally reversible stimulus-sensitive gel or gelling copolymer radioisotope carrier that is a linear random copolymer of an [meth]acrylamide derivative and a hydrophilic comonomer, wherein the linear random copolymer is in the form of a plurality of linear chains having a plurality of molecular weights greater than or equal to a minimum gelling molecular weight cutoff. Addition of a biodegradable backbone and/or a therapeutic agent imparts further utility. The method of the present invention for making a thermally reversible stimulus-sensitive gelling copolymer radionuclcide carrier has the steps of: (a) mixing a stimulus-sensitive reversible gelling copolymer with an aqueous solvent as a stimulus-sensitive reversible gelling solution; and (b) mixing a radioisotope with said stimulus-sensitive reversible gelling solution as said radioisotope carrier. The gel is enhanced by either combining it with a biodegradable backbone and/or a therapeutic agent in a gelling solution made by mixing the copolymer with an aqueous solvent.

  5. Advanced radioisotope power source options for Pluto Express

    SciTech Connect

    Underwood, M.L.

    1995-12-31

    In the drive to reduce mass and cost, Pluto Express is investigating using an advanced power conversion technology in a small Radioisotope Power Source (RPS) to deliver the required mission power of 74 W(electric) at end of mission. Until this year the baseline power source under consideration has been a Radioisotope Thermoelectric Generator (RTG). This RTG would be a scaled down GPHS RTG with an inventory of 6 General Purpose Heat Sources (GPHS) and a mass of 17.8 kg. High efficiency, advanced technology conversion options are being examined to lower the power source mass and to reduce the amount of radioisotope needed. Three technologies are being considered as the advanced converter technology: the Alkali Metal Thermal-to-Electric Converter (AMTEC), Thermophotovoltaic (TPV) converters, and Stirling Engines. Conceptual designs for each of these options have been prepared. Each converter would require only 2 GPHSs to provide the mission power and would have a mass of 6.1, 7.2, and 12.4 kg for AMTEC, TPV, and Stirling Engines respectively. This paper reviews the status of each technology and the projected performance of an advanced RPS based on each technology. Based on the projected performance and spacecraft integration issues, Pluto Express would prefer to use the AMTEC based RPS. However, in addition to technical performance, selection of a power technology will be based on many other factors.

  6. Radioisotope Power: A Key Technology for Deep Space Exploration

    NASA Technical Reports Server (NTRS)

    Schmidt, George; Sutliff, Tom; Dudzinski, Leonard

    2008-01-01

    A Radioisotope Power System (RPS) generates power by converting the heat released from the nuclear decay of radioactive isotopes, such as Plutonium-238 (Pu-238), into electricity. First used in space by the U.S. in 1961, these devices have enabled some of the most challenging and exciting space missions in history, including the Pioneer and Voyager probes to the outer solar system; the Apollo lunar surface experiments; the Viking landers; the Ulysses polar orbital mission about the Sun; the Galileo mission to Jupiter; the Cassini mission orbiting Saturn; and the recently launched New Horizons mission to Pluto. Radioisotopes have also served as a versatile heat source for moderating equipment thermal environments on these and many other missions, including the Mars exploration rovers, Spirit and Opportunity. The key advantage of RPS is its ability to operate continuously, independent of orientation and distance relative to the Sun. Radioisotope systems are long-lived, rugged, compact, highly reliable, and relatively insensitive to radiation and other environmental effects. As such, they are ideally suited for missions involving long-lived, autonomous operations in the extreme conditions of space and other planetary bodies. This paper reviews the history of RPS for the U.S. space program. It also describes current development of a new Stirling cycle-based generator that will greatly expand the application of nuclear-powered missions in the future.

  7. Radioisotope Electric Propulsion Centaur Orbiter Spacecraft Design Overview

    NASA Technical Reports Server (NTRS)

    Oleson, Steve; McGuire, Melissa; Sarver-Verhey, Tim; Juergens, Jeff; Parkey, Tom; Dankanich, John; Fiehler, Doug; Gyekenyesi, John; Hemminger, Joseph; Gilland, Jim; Colozza, Tony; Packard, Tom; Nguyen, Thahn; Schmitz, Paul; Ostdiek, Paul; Gold, Rob; Lisse, Carey; Hibbits, Karl

    2009-01-01

    Radioisotope electric propulsion (REP) has been shown in past studies to enable missions to outerplanetary bodies including the orbiting of Centaur asteroids. Key to the feasibility for REP missions are long life, low power electric propulsion (EP) devices, low mass radioisotope power systems (RPS) and light spacecraft (S/C) components. In order to determine what are the key parameters for EP devices to perform these REP missions a design study was completed to design an REP S/C to orbit a Centaur in a New Frontiers cost cap. The design shows that an orbiter using several long lived (approximately 200 kg Xenon throughput), low power (approximately 700 W) Hall thrusters teamed with six (150 W each) Advanced Stirling Radioisotope Generators (ASRG) can deliver 60 kg of science instruments to a Centaur in 10 yr within the New Frontiers cost cap. Optimal specific impulses for the Hall thrusters were found to be around 2000 sec with thruster efficiencies over 40%. Not only can the REP S/C enable orbiting a Centaur (when compared to an all chemical mission only capable of flybys) but the additional power from the REP system can be reused to enhance science and simplify communications.

  8. NASA's Radioisotope Power Systems Planning and Potential Future Systems Overview

    NASA Technical Reports Server (NTRS)

    Zakrajsek, June F.; Woerner, Dave F.; Cairns-Gallimore, Dirk; Johnson, Stephen G.; Qualis, Louis

    2016-01-01

    The goal of NASA's Radioisotope Power Systems (RPS) Program is to make RPS ready and available to support the exploration of the solar system in environments where the use of conventional solar or chemical power generation is impractical or impossible to meet the needs of the missions. To meet this goal, the RPS Program, working closely with the Department of Energy, performs mission and system studies (such as the recently released Nuclear Power Assessment Study), assesses the readiness of promising technologies to infuse in future generators, assesses the sustainment of key RPS capabilities and knowledge, forecasts and tracks the Programs budgetary needs, and disseminates current information about RPS to the community of potential users. This process has been refined and used to determine the current content of the RPS Programs portfolio. This portfolio currently includes an effort to mature advanced thermoelectric technology for possible integration into an enhanced Multi-Mission Radioisotope Generator (eMMRTG), sustainment and production of the currently deployed MMRTG, and technology investments that could lead to a future Stirling Radioisotope Generator (SRG). This paper describes the program planning processes that have been used, the currently available MMRTG, and one of the potential future systems, the eMMRTG.

  9. Hafnium radioisotope recovery from irradiated tantalum

    DOEpatents

    Taylor, Wayne A.; Jamriska, David J.

    2001-01-01

    Hafnium is recovered from irradiated tantalum by: (a) contacting the irradiated tantalum with at least one acid to obtain a solution of dissolved tantalum; (b) combining an aqueous solution of a calcium compound with the solution of dissolved tantalum to obtain a third combined solution; (c) precipitating hafnium, lanthanide, and insoluble calcium complexes from the third combined solution to obtain a first precipitate; (d) contacting the first precipitate of hafnium, lanthanide and calcium complexes with at least one fluoride ion complexing agent to form a fourth solution; (e) selectively adsorbing lanthanides and calcium from the fourth solution by cationic exchange; (f) separating fluoride ion complexing agent product from hafnium in the fourth solution by adding an aqueous solution of ferric chloride to obtain a second precipitate containing the hafnium and iron; (g) dissolving the second precipitate containing the hafnium and iron in acid to obtain an acid solution of hafnium and iron; (h) selectively adsorbing the iron from the acid solution of hafnium and iron by anionic exchange; (i) drying the ion exchanged hafnium solution to obtain hafnium isotopes. Additionally, if needed to remove residue remaining after the product is dried, dissolution in acid followed by cation exchange, then anion exchange, is performed.

  10. Real-time monitoring during transportation of a radioisotope thermoelectric generator (RTG) using the radioisotope thermoelectric generator transportation system (RTGTS)

    NASA Astrophysics Data System (ADS)

    Pugh, Barry K.

    1997-01-01

    The Radioisotopic Thermoelectric Generators (RTGs) that will be used to support the Cassini mission will be transported in the Radioisotope Thermoelectric Generator Transportation System (RTGTS). To ensure that the RTGs will not be affected during transportation, all parameters that could adversely affect RTG's performance must be monitored. The Instrumentation and Data Acquisition System (IDAS) for the RTGTS displays, monitors, and records all critical packaging and trailer system parameters. The IDAS also monitors the package temperature control system, RTG package shock and vibration data, and diesel fuel levels for the diesel fuel tanks. The IDAS alarms if any of these parameters reach an out-of-limit condition. This paper discusses the real-time monitoring during transportation of the Cassini RTGs using the RTGTS IDAS.

  11. Dynamic Radioisotope Power System Development for Space Explorations

    SciTech Connect

    Qualls, A L

    2017-01-01

    Dynamic power conversion offers the potential to produce radioisotope power systems (RPS) that generate higher power outputs and utilize the Pu-238 radioisotope more efficiently than Radioisotope Thermoelectric Generators (RTG). Additionally, dynamic systems also offer the potential of producing generators with significantly reduced power degradation over the course of deep space missions so that more power will be available at the end of the mission when it is needed for both powering the science and transmitting the results. The development of dynamic generators involves addressing technical issues not typically associated with traditional thermoelectric generators. Developing long-life, robust and reliable dynamic conversion technology is challenging yet essential to building a suitable generator. Considerations include working within existing handling infrastructure where possible so that development costs can be kept low and integrating dynamic generators into spacecraft, which may be more complex than integration of static systems. Methods of interfacing to and controlling a dynamic generator must be considered and new potential failure modes must be taken into account. This paper will address some of the key issues of dynamic RPS design, development and adaption.Dynamic power conversion offers the potential to produce Radioisotope Power Systems (RPS) that generate higher power outputs and utilize the available heat source plutonium fuel more efficiently than Radioisotope Thermoelectric Generators. Additionally, dynamic systems offer the potential of producing generators with significantly reduced power degradation over the course of deep space missions so that more power would be available at the end of the mission, when it is needed most for both powering science instruments and transmitting the resulting data. The development of dynamic generators involves addressing technical issues not typically associated with traditional thermoelectric generators

  12. Work Began on Contracts for Radioisotope Power Conversion Technology Research and Development

    NASA Technical Reports Server (NTRS)

    Wong, Wayne A.

    2005-01-01

    NASA has had a history of successful space flight missions that depended on radioisotope-fueled power systems. These Radioisotope Power Systems (RPSs) converted the heat generated from the decay of radioisotope material into useful electrical power. An RPS is most attractive in applications where photovoltaics are not optimal, such as deep-space applications where the solar flux is too low or extended applications on planets such as Mars where the day/night cycle, settling of dust, and life requirements limit the usefulness of photovoltaics. NASA s Radioisotope Power Conversion Technology (RPCT) Program is developing next-generation power-conversion technologies that will enable future missions that have requirements that cannot be met by the two RPS flight systems currently being developed by the Department of Energy for NASA: the Multi-Mission Radioisotope Thermoelectric Generator and the Stirling Radioisotope Generator (SRG).

  13. GEANT4 simulation of cyclotron radioisotope production in a solid target.

    PubMed

    Poignant, F; Penfold, S; Asp, J; Takhar, P; Jackson, P

    2016-05-01

    The use of radioisotopes in nuclear medicine is essential for diagnosing and treating cancer. The optimization of their production is a key factor in maximizing the production yield and minimizing the associated costs. An efficient approach to this problem is the use of Monte Carlo simulations prior to experimentation. By predicting isotopes yields, one can study the isotope of interest expected activity for different energy ranges. One can also study the target contamination with other radioisotopes, especially undesired radioisotopes of the wanted chemical element which are difficult to separate from the irradiated target and might result in increasing the dose when delivering the radiopharmaceutical product to the patient. The aim of this work is to build and validate a Monte Carlo simulation platform using the GEANT4 toolkit to model the solid target system of the South Australian Health and Medical Research Institute (SAHMRI) GE Healthcare PETtrace cyclotron. It includes a GEANT4 Graphical User Interface (GUI) where the user can modify simulation parameters such as the energy, shape and current of the proton beam, the target geometry and material, the foil geometry and material and the time of irradiation. The paper describes the simulation and presents a comparison of simulated and experimental/theoretical yields for various nuclear reactions on an enriched nickel 64 target using the GEANT4 physics model QGSP_BIC_AllHP, a model recently developed to evaluate with high precision the interaction of protons with energies below 200MeV available in Geant4 version 10.1. The simulation yield of the (64)Ni(p,n)(64)Cu reaction was found to be 7.67±0.074 mCi·μA(-1) for a target energy range of 9-12MeV. Szelecsenyi et al. (1993) gives a theoretical yield of 6.71mCi·μA(-1) and an experimental yield of 6.38mCi·μA(-1). The (64)Ni(p,n)(64)Cu cross section obtained with the simulation was also verified against the yield predicted from the nuclear database TENDL and

  14. Development of Advanced Stirling Radioisotope Generator for Space Exploration

    NASA Technical Reports Server (NTRS)

    Chan, Jack; Wood, J. Gary; Schreiber, Jeffrey G.

    2007-01-01

    Under the joint sponsorship of the Department of Energy and NASA, a radioisotope power system utilizing Stirling power conversion technology is being developed for potential future space missions. The higher conversion efficiency of the Stirling cycle compared with that of Radioisotope Thermoelectric Generators (RTGs) used in previous missions (Viking, Pioneer, Voyager, Galileo, Ulysses, Cassini, and New Horizons) offers the advantage of a four-fold reduction in PuO2 fuel, thereby saving cost and reducing radiation exposure to support personnel. With the advancement of state-of-the-art Stirling technology development under the NASA Research Announcement (NRA) project, the Stirling Radioisotope Generator program has evolved to incorporate the advanced Stirling convertor (ASC), provided by Sunpower, into an engineering unit. Due to the reduced envelope and lighter mass of the ASC compared to the previous Stirling convertor, the specific power of the flight generator is projected to increase from 3.5 to 7 We/kg, along with a 25 percent reduction in generator length. Modifications are being made to the ASC design to incorporate features for thermal, mechanical, and electrical integration with the engineering unit. These include the heat collector for hot end interface, cold-side flange for waste heat removal and structural attachment, and piston position sensor for ASC control and power factor correction. A single-fault tolerant, active power factor correction controller is used to synchronize the Stirling convertors, condition the electrical power from AC to DC, and to control the ASCs to maintain operation within temperature and piston stroke limits. Development activities at Sunpower and NASA Glenn Research Center (GRC) are also being conducted on the ASC to demonstrate the capability for long life, high reliability, and flight qualification needed for use in future missions.

  15. Joint Radioisotope Electric Propulsion Studies - Neptune System Explorer

    NASA Technical Reports Server (NTRS)

    Khan, M. Omair; Amini, Rashied; Ervin, Joan; Lang, Jared; Landau, Damon; Oleson, Steven; Spilker, Thomas; Strange, Nathan

    2011-01-01

    The Neptune System Explorer (NSE) mission concept study assessed opportunities to conduct Cassini-like science at Neptune with a radioisotope electric propulsion (REP) based spacecraft. REP is based on powering an electric propulsion (EP) engine with a radioisotope power source (RPS). The NSE study was commissioned under the Joint Radioisotope Electric Propulsion Studies (JREPS) project, which sought to determine the technical feasibility of flagship class REP applications. Within JREPS, special emphasis was given toward identifying tall technology tent poles, as well as recommending any new RPS technology developments that would be required for complicated REP missions. Based on the goals of JREPS, multiple RPS (e.g. thermoelectric and Stirling based RPS) and EP (e.g. Hall and ion engines) technology combinations were traded during the NSE study to determine the most favorable REP design architecture. Among the findings from the study was the need for >400We RPS systems, which was driven by EP operating powers and the requirement for a long-lived mission in the deep solar system. Additionally multiple development and implementation risks were identified for the NSE concept, as well as REP missions in general. Among the strengths of the NSE mission would be the benefits associated with RPS and EP use, such as long-term power (approx. 2-3kW) at Neptune and flexible trajectory options for achieving orbit or tours of the Neptune system. Although there are still multiple issues to mitigate, the NSE concept demonstrated distinct advantages associated with using REP for deep space flagship-class missions.

  16. Development of Advanced Stirling Radioisotope Generator for Space Exploration

    NASA Astrophysics Data System (ADS)

    Chan, Jack; Wood, J. Gary; Schreiber, Jeffrey G.

    2007-01-01

    Under the joint sponsorship of the Department of Energy and NASA, a radioisotope power system utilizing Stirling power conversion technology is being developed for potential future space missions. The higher conversion efficiency of the Stirling cycle compared with that of Radioisotope Thermoelectric Generators (RTGs) used in previous missions (Viking, Pioneer, Voyager, Galileo, Ulysses, Cassini, and New Horizons) offers the advantage of a four-fold reduction in PuO2 fuel, thereby saving cost and reducing radiation exposure to support personnel. With the advancement of state-of-the-art Stirling technology development under the NASA Research Announcement (NRA) project, the Stirling Radioisotope Generator program has evolved to incorporate the advanced Stirling convertor (ASC), provided by Sunpower, into an engineering unit. Due to the reduced envelope and lighter mass of the ASC compared to the previous Stirling convertor, the specific power of the flight generator is projected to increase from 3.5 We/kg to 7 We/kg, along with a 25% reduction in generator length. Modifications are being made to the ASC design to incorporate features for thermal, mechanical, and electrical integration with the engineering unit. These include the heat collector for hot end interface, cold-side flange for waste heat removal and structural attachment, and piston position sensor for ASC control and power factor correction. A single-fault tolerant, active power factor correction controller is used to synchronize the Stirling convertors, condition the electrical power from AC to DC, and to control the ASCs to maintain operation within temperature and piston stroke limits. Development activities at Sunpower and NASA Glenn Research Center (GRC) are also being conducted on the ASC to demonstrate the capability for long life, high reliability, and flight qualification needed for use in future missions.

  17. Radioisotope thermoelectric generator licensed hardware package and certification tests

    NASA Astrophysics Data System (ADS)

    Goldmann, Louis H.; Averette, Henry S.

    1995-01-01

    This paper presents the Licensed Hardware package and the Certification Test portions of the Radioisitope Themoelectric Generator Transportation System. This package has been designed to meet those portions of the Code of Federal Regulations (10 CFR 71) relating to ``Type B'' shipments of radioactive materials. The licensed hardware is now in the U. S. Department of Energy licensing process that certifies the packaging's integrity under accident conditions. The detailed information for the anticipated license is presented in the safety analysis report for packaging, which is now in process and undergoing necessary reviews. As part of the licensing process, a full-size Certification Test Article unit, which has modifications slightly different than the Licensed Hardware or production shipping units, is used for testing. Dimensional checks of the Certification Test Article were made at the manufacturing facility. Leak testing and drop testing were done at the 300 Area of the U.S. Department of Energy's Hanford Site near Richland, Washington. The hardware includes independent double containments to prevent the environmental spread of 238Pu, impact limiting devices to protect portions of the package from impacts, and thermal insulation to protect the seal areas from excess heat during accident conditions. The package also features electronic feed-throughs to monitor the Radioisotope Thermoelectric Generator's temperature inside the containment during the shipment cycle. This package is designed to safely dissipate the typical 4,500 thermal watts produced in the largest Radioisotope Thermoelectric Generators. The package also contains provisions to ensure leak tightness when radioactive materials, such as a Radioisotope Thermoelectric Generator for the Cassini Mission, planned for 1997 by the National Aeronautics and Space Administration, are being prepared for shipment. These provisions include test ports used in conjunction with helium mass spectrometers to determine

  18. Radioisotope Stirling Generator Options for Pluto Fast Flyby Mission

    SciTech Connect

    Schock, Alfred

    1993-10-01

    The preceding paper described conceptual designs and analytical results for five Radioisotope Thermoelectric Generator (RTG) options for the Pluto Fast Flyby (PFF) mission, and the present paper describes three Radioisotope Stirling Generator (RSG) options for the same mission. The RSG options are based on essentially the same radioisotope heat source modules used in previously flown RTGs and on designs and analyses of a 75-watt free-piston Stirling engine produced by Mechanical Technology Incorporated (MTI) for NASA's Lewis Research Center. The integrated system design options presented were generated in a Fairchild Space study sponsored by the Department of Energy's Office of Special Applications, in support of ongoing PFF mission and spacecraft studies that the Jet Propulsion Laboratory (JPL) is conducting for the National Aeronautics and Space Administration (NASA). That study's NASA-directed goal is to reduce the spacecraft mass from its baseline value of 166 kg to ~110 kg, which implies a mass goal of less than 10 kg for a power source able to deliver 69 watts(e) at the end of the 9.2-year mission. In general, the Stirling options were found to be lighter than the thermoelectric options described in the preceding paper. But they are less mature, requiring more development, and entailing greater programmatic risk. The Stirling power system mass ranged from 7.3 kg (well below the 10-kg goal) for a non-redundant system to 11.3 kg for a redundant system able to maintain full power if one of its engines fails. In fact, the latter system could deliver as much as 115 watts(e) if desired by the mission planners. There are 5 copies in the file.

  19. Joint Radioisotope Electric Propulsion Studies - Neptune System Explorer

    NASA Technical Reports Server (NTRS)

    Khan, M. Omair; Amini, Rashied; Ervin, Joan; Lang, Jared; Landau, Damon; Oleson, Steven; Spilker, Thomas; Strange, Nathan

    2011-01-01

    The Neptune System Explorer (NSE) mission concept study assessed opportunities to conduct Cassini-like science at Neptune with a radioisotope electric propulsion (REP) based spacecraft. REP is based on powering an electric propulsion (EP) engine with a radioisotope power source (RPS). The NSE study was commissioned under the Joint Radioisotope Electric Propulsion Studies (JREPS) project, which sought to determine the technical feasibility of flagship class REP applications. Within JREPS, special emphasis was given toward identifying tall technology tent poles, as well as recommending any new RPS technology developments that would be required for complicated REP missions. Based on the goals of JREPS, multiple RPS (e.g. thermoelectric and Stirling based RPS) and EP (e.g. Hall and ion engines) technology combinations were traded during the NSE study to determine the most favorable REP design architecture. Among the findings from the study was the need for >400We RPS systems, which was driven by EP operating powers and the requirement for a long-lived mission in the deep solar system. Additionally multiple development and implementation risks were identified for the NSE concept, as well as REP missions in general. Among the strengths of the NSE mission would be the benefits associated with RPS and EP use, such as long-term power (approx. 2-3kW) at Neptune and flexible trajectory options for achieving orbit or tours of the Neptune system. Although there are still multiple issues to mitigate, the NSE concept demonstrated distinct advantages associated with using REP for deep space flagship-class missions.

  20. Development of Next Generation Segmented Thermoelectric Radioisotope Power Systems

    NASA Astrophysics Data System (ADS)

    Fleurial, J.; Caillat, T.; Ewell, R. C.

    2005-12-01

    Radioisotope thermoelectric generators have been used for space-based applications since 1961 with a total of 22 space missions that have successfully used RTGs for electrical power production. The key advantages of radioisotope thermoelectric generators (RTGs) are their long life, robustness, compact size, and high reliability. Thermoelectric converters are easily scalable, and possess a linear current-voltage curve, making power generation easy to control via a shunt regulator and shunt radiator. They produce no noise, vibration or torque during operation. These properties have made RTGs ideally suitable for autonomous missions in the extreme environments of outer space and on planetary surfaces. More advanced radioisotope power systems (RPS) with higher specific power (W/kg) and/or power output are desirable for future NASA missions, including the Europa Geophysical Orbiter mission. For the past few years, the Jet Propulsion Laboratory (JPL) has been developing more efficient thermoelectric materials and has demonstrated significant increases in the conversion efficiency of high temperature thermocouples, up to 14% when operated across a 975K to 300K temperature differential. In collaboration with NASA Glenn Research Center, universities (USC and UNM), Ceramic and Metal Composites Corporation and industrial partners, JPL is now planning to lead the research and development of advanced thermoelectric technology for integration into the next generations of RPS. Preliminary studies indicate that this technology has the potential for improving the RPS specific power by more than 50% over the current state-of-the-art multi-mission RTG being built for the Mars Science Laboratory mission. A second generation advanced RPS is projected at more than doubling the specific power.

  1. Radioisotope Stirling Generator Options for Pluto Fast Flyby Mission

    NASA Astrophysics Data System (ADS)

    Schock, Alfred

    1994-07-01

    The preceding paper (Schock 1994) described conceptual designs and analytical results for five Radioisotope Thermoelectric Generator (RTG) options for the Pluto Fast Flyby (PFF) mission, and the present paper describes three Radioisotope Stirling Generator (RSG) options for the same mission. The RSG options are based on essentially the same radioisotope heat source modules used in previously flown RTGs and on designs and analyses of a 75-Watt free-piston Stirling engine produced by Mechanical Technology Incorporated (MTI) for NASA's Lewis Research Center. The integrated system design options presented were generated in a Fairchild Space study sponsored by the Department of Energy's Office of Special Applications, in support of ongoing PFF mission and spacecraft studies that the Jet Propulsion Laboratory (JPL) is conducting for the National Aeronautics and Space Administration (NASA). That study's NASA-directed goal is to reduce the spacecraft mass from its baseline value of 166 kg to -110 kg, which implies a mass goal of less than 10 kg for a power source able to deliver 69 Watts(e) at the end of the 9.2-year mission. In general, the Stirling options were found to be lighter than the thermoelectric options described in the preceding paper. But they are less mature, requiring more development, and entailing greater programmatic risk. The Stirling power system mass ranged from 7.3 kg (well below the 10-kg goal) for a non-redundant system to 11.3 kg for a redundant system able to maintain full power if one of its two engines fails. In fact, the latter system could deliver as much as 115 Watts(e) if desired by the mission planners.

  2. Radioisotope Stirling Generator Options for Pluto Fast Flyby Mission

    SciTech Connect

    Schock, Alfred

    2012-01-19

    The preceding paper described conceptual designs and analytical results for five Radioisotope Thermoelectric Generator (RTG) options for the Pluto Fast Flyby (PFF) mission, and the present paper describes three Radioisotope Stirling Generator (RSG) options for the same mission. The RSG options are based on essentially the same radioisotope heat source modules used in previously flown RTGs and on designs and analyses of a 75-watt free-piston Stirling engine produced by Mechanical Technology Incorporated (MTI) for NASA's Lewis Research Center. The integrated system design options presented were generated in a Fairchild Space study sponsored by the Department of Energy's Office of Special Applications, in support of ongoing PFF mission and spacecraft studies that the Jet Propulsion Laboratory (JPL) is conducting for the National Aeronautics and Space Administration (NASA). That study's NASA-directed goal is to reduce the spacecraft mass from its baseline value of 166 kg to ~110 kg, which implies a mass goal of less than 10 kg for a power source able to deliver 69 watts(e) at the end of the 9.2-year mission. In general, the Stirling options were found to be lighter than the thermoelectric options described in the preceding paper. But they are less mature, requiring more development, and entailing greater programmatic risk. The Stirling power system mass ranged from 7.3 kg (well below the 10-kg goal) for a non-redundant system to 11.3 kg for a redundant system able to maintain full power if one of its engines fails. In fact, the latter system could deliver as much as 115 watts(e) if desired by the mission planners. There are 2 copies in the file.

  3. Utilizing Radioisotope Power System Waste Heat for Spacecraft Thermal Management

    NASA Technical Reports Server (NTRS)

    Pantano, David R.; Dottore, Frank; Geng, Steven M.; Schrieber, Jeffrey G.; Tobery, E. Wayne; Palko, Joseph L.

    2005-01-01

    One of the advantages of using a Radioisotope Power System (RPS) for deep space or planetary surface missions is the readily available waste heat, which can be used to maintain electronic components within a controlled temperature range, to warm propulsion tanks and mobility actuators, and to gasify liquid propellants. Previous missions using Radioisotope Thermoelectric Generators (RTGs) dissipated a very large quantity of waste heat due to the relatively low efficiency of the thermoelectric conversion technology. The next generation RPSs, such as the 110-watt Stirling Radioisotope Generator (SRG110) will have much higher conversion efficiencies than their predecessors and therefore may require alternate approaches to transferring waste heat to the spacecraft. RTGs, with efficiencies of approx. 6 to 7% and 200 C housing surface temperatures, would need to use large and heavy radiator heat exchangers to transfer the waste heat to the internal spacecraft components. At the same time, sensitive spacecraft instruments must be shielded from the thermal radiation by using the heat exchangers or additional shields. The SRG110, with an efficiency around 22% and 50 C nominal housing surface temperature, can use the available waste heat more efficiently by more direct heat transfer methods such as heat pipes, thermal straps, or fluid loops. The lower temperatures allow the SRG110 much more flexibility to the spacecraft designers in configuring the generator without concern of overheating nearby scientific instruments, thereby eliminating the need for thermal shields. This paper will investigate using a high efficiency SRG110 for spacecraft thermal management and outline potential methods in several conceptual missions (Lunar Rover, Mars Rover, and Titan Lander) to illustrate the advantages with regard to ease of assembly, less complex interfaces, and overall mass savings.

  4. Milliwatt radioisotope power supply for the PASCAL Mars surface stations

    NASA Astrophysics Data System (ADS)

    Allen, Daniel T.; Murbach, Marcus S.

    2001-02-01

    A milliwatt power supply is being developed based on the 1 watt Light-Weight Radioisotope Heater Unit (RHU), which has already been used to provide heating alone on numerous spacecraft. In the past year the power supply has been integrated into the design of the proposed PASCAL Mars Network Mission, which is intended to place 24 surface climate monitoring stations on Mars. The PASCAL Mars mission calls for the individual surface stations to be transported together in one spacecraft on a trajectory direct from launch to orbit around Mars. From orbit around Mars each surface station will be deployed on a SCRAMP (slotted compression ramp) probe and, after aerodynamic and parachute deceleration, land at a preselected location on the planet. During descent sounding data and still images will be accumulated, and, once on the surface, the station will take measurements of pressure, temperature and overhead atmospheric optical depth for a period of 10 Mars years (18.8 Earth years). Power for periodic data acquisition and transmission to orbital then to Earth relay will come from a bank of ultracapacitors which will be continuously recharged by the radioisotope power supply. This electronic system has been designed and a breadboard built. In the ultimate design the electronics will be arrayed on the exterior surface of the radioisotope power supply in order to take advantage of the reject heat. This assembly in turn is packaged within the SCRAMP, and that assembly comprises the surface station. An electrically heated but otherwise prototypical power supply was operated in combination with the surface station breadboard system, which included the ultracapacitors. Other issues addressed in this work have been the capability of the generator to withstand the mechanical shock of the landing on Mars and the effectiveness of the generator's multi-foil vacuum thermal insulation. .

  5. Analytical predictions of RTG power degradation. [Radioisotope Thermoelectric Generator

    NASA Technical Reports Server (NTRS)

    Noon, E. L.; Raag, V.

    1979-01-01

    The DEGRA computer code that is based on a mathematical model which predicts performance and time-temperature dependent degradation of a radioisotope thermoelectric generator is discussed. The computer code has been used to predict performance and generator degradation for the selenide Ground Demonstration Unit (GDS-1) and the generator used in the Galileo Project. Results of parametric studies of load voltage vs generator output are examined as well as the I-V curve and the resulting predicted power vs voltage. The paper also discusses the increased capability features contained in DEGRA2 and future plans for expanding the computer code performance.

  6. The use of radioisotopes for palliation of metastatic bone pain.

    PubMed

    Gkialas, I; Iordanidou, L; Galanakis, I; Giannopoulos, S

    2008-01-01

    Bone pain associated with advanced prostate and other cancers is a frequent and significant complication. Pharmaceutical therapy of bone pain includes nonsteroidal analgesics and opiates. While external beam radiation therapy remains the mainstay of pain palliation of solitary lesions, bone-seeking radiopharmaceuticals have entered the armamentarium for the treatment of multiple osseous metastases. The 3 radioisotopes currently approved for treatment of pain (strontium-89/(89)Sr, samarium-153/(153)Sm and rhenium-186/(186)Re) are discussed in this review including the approved dose, method of administration and indications for use.

  7. Parametric System Model for a Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.

    2014-01-01

    A Parametric System Model (PSM) was created in order to explore conceptual designs, the impact of component changes and power level on the performance of Stirling Radioisotope Generator (SRG). Using the General Purpose Heat Source (GPHS approximately 250 watt thermal) modules as the thermal building block around which a SRG is conceptualized, trade studies are performed to understand the importance of individual component scaling on isotope usage. Mathematical relationships based on heat and power throughput, temperature, mass and volume were developed for each of the required subsystems. The PSM uses these relationships to perform component and system level trades.

  8. Parametric System Model for a Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Schmitz, Paul C.

    2015-01-01

    A Parametric System Model (PSM) was created in order to explore conceptual designs, the impact of component changes and power level on the performance of the Stirling Radioisotope Generator (SRG). Using the General Purpose Heat Source (GPHS approximately 250 Wth) modules as the thermal building block from which a SRG is conceptualized, trade studies are performed to understand the importance of individual component scaling on isotope usage. Mathematical relationships based on heat and power throughput, temperature, mass, and volume were developed for each of the required subsystems. The PSM uses these relationships to perform component- and system-level trades.

  9. Radioisotope measurement of the velocity of tracheal mucus

    SciTech Connect

    Russo, K.J.; Palmer, D.W.; Beste, D.J.; Carl, G.A.; Belson, T.P.; Pelc, L.R.; Toohill, R.J.

    1985-04-01

    A radioisotope scanning technique for measuring the velocity of tracheal mucus has been developed utilizing a canine model. A solution of stannous phytate labeled with /sup 99m/Tc is introduced percutaneously into the lower trachea and the upward movement of the leading edge of the radioactivity is followed by repeat scanning at 2-minute intervals using a modified rectilinear scanner, thus allowing calculation of the velocity of the mucus. It is believed that this technique may be of value in studying the effect of experimentally induced tracheal injuries on mucus velocity. Possible applications of the technique for the study of the velocity of mucus in the human trachea are discussed.

  10. Nuclear reactors for research and radioisotope production in Argentina

    SciTech Connect

    Duran, H.H.

    1981-01-01

    In Argentina, the construction, operation, and use of research and radioisotope production reactors is and has been an important method of personnel preparation for the nuclear power program. Moreover, it is a very suitable means for technology transfer to countries developing their own nuclear programs. At present, the following research reactors are in operation in Argentina: Argentine Reactor 0 (RA-0); Argentine Reactor 1 (RA-1); Argentine Reactor 2 (RA-2); Argentine Reactor 3 (RA-3); Argentine Reactor 4 (RA-4). The Argentine Reactor 6 (RA-6), under construction, should reach criticality in 1981.

  11. Accreditation experience of radioisotope metrology laboratory of Argentina.

    PubMed

    Iglicki, A; Milá, M I; Furnari, J C; Arenillas, P; Cerutti, G; Carballido, M; Guillén, V; Araya, X; Bianchini, R

    2006-01-01

    This work presents the experience developed by the Radioisotope Metrology Laboratory (LMR), of the Argentine National Atomic Energy Commission (CNEA), as result of the accreditation process of the Quality System by ISO 17025 Standard. Considering the LMR as a calibration laboratory, services of secondary activity determinations and calibration of activimeters used in Nuclear Medicine were accredited. A peer review of the (alpha/beta)-gamma coincidence system was also carried out. This work shows in detail the structure of the quality system, the results of the accrediting audit and gives the number of non-conformities detected and of observations made which have all been resolved.

  12. Lightweight Radioisotope Heater Unit (LWRHU) production for the Cassini mission

    SciTech Connect

    Rinehart, G.H.

    1996-06-01

    The Lightweight Radioisotope Heater Unit (LWRHU) is a {sup 238}PuO{sub 2} fueled heat source designed to provide a thermal watt of power for space missions. The LWRHU will be used to maintain the temperature of various components on the spacecraft at the required level. The heat source consists of a {sup 238}PuO{sub 2} fuel pellet, a Pt-30Rh capsule, a pyrolytic graphite insulator, and a woven graphite aeroshell assembly. Los Alamos has fabricated 180 heater units, which will be used on the Cassini mission. This report summarizes the specifications, fabrication processes, and production data for the heat sources fabricated at Los Alamos.

  13. Energy-Recovery Linacs for Commercial Radioisotope Production

    SciTech Connect

    Johnson, Rolland Paul

    2016-11-19

    Most radioisotopes are produced by nuclear reactors or positive ion accelerators, which are expensive to construct and to operate. Photonuclear reactions using bremsstrahlung photon beams from less-expensive electron linacs can generate isotopes of critical interest, but much of the beam energy in a conventional electron linac is dumped at high energy, making unwanted radioactivation. The largest part of this radioactivation may be completely eliminated by applying energy recovery linac technology to the problem with an additional benefit that the energy cost to produce a given amount of isotope is reduced. Consequently, a Superconducting Radio Frequency (SRF) Energy Recovery Linac (ERL) is a path to a more diverse and reliable domestic supply of short-lived, high-value, high-demand isotopes at a cost lower than that of isotopes produced by reactors or positive-ion accelerators. A Jefferson Lab approach to this problem involves a thin photon production radiator, which allows the electron beam to recirculate through rf cavities so the beam energy can be recovered while the spent electrons are extracted and absorbed at a low enough energy to minimize unwanted radioactivation. The thicker isotope photoproduction target is not in the beam. MuPlus, with Jefferson Lab and Niowave, proposed to extend this ERL technology to the commercial world of radioisotope production. In Phase I we demonstrated that 1) the ERL advantage for producing radioisotopes is at high energies (~100 MeV), 2) the range of acceptable radiator thickness is narrow (too thin and there is no advantage relative to other methods and too thick means energy recovery is too difficult), 3) using optics techniques developed under an earlier STTR for collider low beta designs greatly improves the fraction of beam energy that can be recovered (patent pending), 4) many potentially useful radioisotopes can be made with this ERL technique that have never before been available in significant commercial quantities

  14. ADVANCED RADIOISOTOPE HEAT SOURCE AND PROPULSION SYSTEMS FOR PLANETARY EXPLORATION

    SciTech Connect

    R. C. O'Brien; S. D. Howe; J. E. Werner

    2010-09-01

    The exploration of planetary surfaces and atmospheres may be enhanced by increasing the range and mobility of a science platform. Fundamentally, power production and availability of resources are limiting factors that must be considered for all science and exploration missions. A novel power and propulsion system is considered and discussed with reference to a long-range Mars surface exploration mission with in-situ resource utilization. Significance to applications such as sample return missions is also considered. Key material selections for radioisotope encapsulation techniques are presented.

  15. Radioisotope Electric Propulsion for Deep Space Sample Return

    SciTech Connect

    Noble, Robert J.; /SLAC

    2009-07-14

    The need to answer basic questions regarding the origin of the Solar System will motivate robotic sample return missions to destinations like Pluto, its satellite Charon, and objects in the Kuiper belt. To keep the mission duration short enough to be of interest, sample return from objects farther out in the Solar System requires increasingly higher return velocities. A sample return mission involves several complicated steps to reach an object and obtain a sample, but only the interplanetary return phase of the mission is addressed in this paper. Radioisotope electric propulsion is explored in this parametric study as a means to propel small, dedicated return vehicles for transferring kilogram-size samples from deep space to Earth. Return times for both Earth orbital rendezvous and faster, direct atmospheric re-entry trajectories are calculated for objects as far away as 100 AU. Chemical retro-rocket braking at Earth is compared to radioisotope electric propulsion but the limited deceleration capability of chemical rockets forces the return trajectories to be much slower.

  16. GRC Supporting Technology for NASA's Advanced Stirling Radioisotope Generator (ASRG)

    NASA Technical Reports Server (NTRS)

    Schreiber, Jeffrey G.; Thieme, Lanny G.

    2008-01-01

    From 1999 to 2006, the NASA Glenn Research Center (GRC) supported a NASA project to develop a high-efficiency, nominal 110-We Stirling Radioisotope Generator (SRG110) for potential use on NASA missions. Lockheed Martin was selected as the System Integration Contractor for the SRG110, under contract to the Department of Energy (DOE). The potential applications included deep space missions, and Mars rovers. The project was redirected in 2006 to make use of the Advanced Stirling Convertor (ASC) that was being developed by Sunpower, Inc. under contract to GRC, which would reduce the mass of the generator and increase the power output. This change would approximately double the specific power and result in the Advanced Stirling Radioisotope Generator (ASRG). The SRG110 supporting technology effort at GRC was replanned to support the integration of the Sunpower convertor and the ASRG. This paper describes the ASRG supporting technology effort at GRC and provides details of the contributions in some of the key areas. The GRC tasks include convertor extended-operation testing in air and in thermal vacuum environments, heater head life assessment, materials studies, permanent magnet characterization and aging tests, structural dynamics testing, electromagnetic interference and electromagnetic compatibility characterization, evaluation of organic materials, reliability studies, and analysis to support controller development.

  17. Multi-Watt Small Radioisotope Thermoelectric Generator Conceptual Design Study

    NASA Astrophysics Data System (ADS)

    Determan, William R.; Otting, William; Frye, Patrick; Abelson, Robert; Ewell, Richard; Miyake, Bob; Synder, Jeff

    2007-01-01

    A need has been identified for a small, light-weight, reliable power source using a radioisotope heat source, to power the next generation of NASA's small surface rovers and exploration probes. Unit performance, development costs, and technical risk are key criteria to be used to select the best design approach. Because safety can be a major program cost and schedule driver, RTG designs should utilize the DOE radioisotope safety program's data base to the maximum extent possible. Other aspects important to the conceptual design include: 1) a multi-mission capable design for atmospheric and vacuum environments, 2) a module size based on one GPHS Step 2 module, 3) use of flight proven thermoelectric converter technologies, 4) a long service lifetime of up to 14 years, 5) maximize unit specific power consistent with all other requirements, and 6) be ready by 2013. Another critical aspect of the design is the thermal integration of the RTG with the rover or probe's heat rejection subsystem and the descent vehicle's heat rejection subsystem. This paper describes two multi-watt RTG design concepts and their integration with a MER-class rover.

  18. An overview of the Radioisotope Thermoelectric Generator Transportation System Program

    NASA Astrophysics Data System (ADS)

    McCoy, John C.; Becker, David L.

    1996-03-01

    Radioisotope Thermoelectric Generators (RTG) convert the heat generated by radioactive decay to electricity using thermocouples. RTGs have a long operating life, are reasonably lightweight, and require little or no maintenance once assembled and tested. These factors make RTGs particularly attractive for use in spacecraft. However, because RTGs contain significant quantities of radioactive materials, normally plutonium-238 and its decay products, they must be transported in packages built in accordance with Title 10, Code of Federal Regulations, Part 71. The U.S. Department of Energy assigned the Radioisotope Thermoelectric Generator Transportation System (RTGTS) Program to Westinghouse Hanford Company in 1988 to develop a system meeting the regulatory requirements. The program objective was to develop a transportation system that would fully comply with 10 CFR 71 while protecting RTGs from adverse environmental conditions during normal conditions of transport (e.g., shock and heat). The RTGTS is scheduled for completion in December 1996 and will be available to support the National Aeronautics and Space Administration's Cassini mission to Saturn in October 1997. This paper provides an overview of the RTGTS and discusses the hardware being produced. Additionally, various program management innovations mandated by recent major changes in the U.S. Department of Energy structure and resources will be outlined.

  19. Technology Development for a Stirling Radioisotope Power System

    NASA Technical Reports Server (NTRS)

    Thieme, Lanny G.; Qiu, Songgang; White, Maurice A.

    2000-01-01

    NASA Glenn Research Center and the Department of Energy are developing a Stirling convertor for an advanced radioisotope power system to provide spacecraft on-board electric power for NASA deep space missions. NASA Glenn is addressing key technology issues through the use of two NASA Phase II SBIRs with Stirling Technology Company (STC) of Kennewick, WA. Under the first SBIR, STC demonstrated a synchronous connection of two thermodynamically independent free-piston Stirling convertors and a 40 to 50 fold reduction in vibrations compared to an unbalanced convertor. The second SBIR is for the development of an Adaptive Vibration Reduction System (AVRS) that will essentially eliminate vibrations over the mission lifetime, even in the unlikely event of a failed convertor. This paper presents the status and results for these two SBIR projects and also discusses a new NASA Glenn in-house project to provide supporting technology for the overall Stirling radioisotope power system development. Tasks for this new effort include convertor performance verification, controls development, heater head structural life assessment, magnet characterization and thermal aging tests, FEA analysis for a lightweight alternator concept, and demonstration of convertor operation under launch and orbit transfer load conditions.

  20. Utilizing Radioisotope Power Systems for Human Lunar Exploration

    NASA Technical Reports Server (NTRS)

    Schreiner, Timothy M.

    2005-01-01

    The Vision for Space Exploration has a goal of sending crewed missions to the lunar surface as early as 2015 and no later than 2020. The use of nuclear power sources could aid in assisting crews in exploring the surface and performing In-Situ Resource Utilization (ISRU) activities. Radioisotope Power Systems (RPS) provide constant sources of electrical power and thermal energy for space applications. RPSs were carried on six of the crewed Apollo missions to power surface science packages, five of which still remain on the lunar surface. Future RPS designs may be able to play a more active role in supporting a long-term human presence. Due to its lower thermal and radiation output, the planned Stirling Radioisotope Generator (SRG) appears particularly attractive for manned applications. The MCNPX particle transport code has been used to model the current SRG design to assess its use in proximity with astronauts operating on the surface. Concepts of mobility and ISRU infrastructure were modeled using MCNPX to analyze the impact of RPSs on crewed mobility systems. Strategies for lowering the radiation dose were studied to determine methods of shielding the crew from the RPSs.

  1. High Temperature Variable Conductance Heat Pipes for Radioisotope Stirling Systems

    NASA Technical Reports Server (NTRS)

    Tarau, Calin; Walker, Kara L.; Anderson, William G.

    2009-01-01

    In a Stirling radioisotope system, heat must continually be removed from the GPHS modules, to maintain the GPHS modules and surrounding insulation at acceptable temperatures. Normally, the Stirling convertor provides this cooling. If the Stirling convertor stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS, but also ending the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) is under development to allow multiple stops and restarts of the Stirling convertor. The status of the ongoing effort in developing this technology is presented in this paper. An earlier, preliminary design had a radiator outside the Advanced Stirling Radioisotope Generator (ASRG) casing, used NaK as the working fluid, and had the reservoir located on the cold side adapter flange. The revised design has an internal radiator inside the casing, with the reservoir embedded inside the insulation. A large set of advantages are offered by this new design. In addition to reducing the overall size and mass of the VCHP, simplicity, compactness and easiness in assembling the VCHP with the ASRG are significantly enhanced. Also, the permanently elevated temperatures of the entire VCHP allows the change of the working fluid from a binary compound (NaK) to single compound (Na). The latter, by its properties, allows higher performance and further mass reduction of the system. Preliminary design and analysis shows an acceptable peak temperature of the ASRG case of 140 C while the heat losses caused by the addition of the VCHP are 1.8 W.

  2. Characterization of the Advanced Stirling Radioisotope Generator EU2

    NASA Technical Reports Server (NTRS)

    Lewandowski, Edward J.; Oriti, Salvatore M.; Schifer, Nicholas A.

    2015-01-01

    Significant progress was made developing the Advanced Stirling Radioisotope Generator (ASRG), a 140-watt radioisotope power system. While the ASRG flight development project has ended, the hardware that was designed and built under the project is continuing to be tested to support future Stirling-based power system development. NASA GRC recently completed the assembly of the ASRG Engineering Unit 2 (EU2). The ASRG EU2 consists of the first pair of Sunpower's ASC-E3 Stirling convertors mounted in an aluminum housing, and Lockheed Martin's Engineering Development Unit (EDU) 4 controller (a fourth generation controller). The ASC-E3 convertors and Generator Housing Assembly (GHA) closely match the intended ASRG Qualification Unit flight design. A series of tests were conducted to characterize the EU2, its controller, and the convertors in the flight-like GHA. The GHA contained an argon cover gas for these tests. The tests included: measurement of convertor, controller, and generator performance and efficiency, quantification of control authority of the controller, disturbance force measurement with varying piston phase and piston amplitude, and measurement of the effect of spacecraft DC bus voltage on EU2 performance. The results of these tests are discussed and summarized, providing a basic understanding of EU2 characteristics and the performance and capability of the EDU 4 controller.

  3. Characterization of the Advanced Stirling Radioisotope Generator Engineering Unit 2

    NASA Technical Reports Server (NTRS)

    Lewandowski, Edward J.; Oriti, Salvatore M.; Schifer, Niholas A.

    2016-01-01

    Significant progress was made developing the Advanced Stirling Radioisotope Generator (ASRG) 140-W radioisotope power system. While the ASRG flight development project has ended, the hardware that was designed and built under the project is continuing to be tested to support future Stirling-based power system development. NASA Glenn Research Center recently completed the assembly of the ASRG Engineering Unit 2 (EU2). The ASRG EU2 consists of the first pair of Sunpower's Advanced Stirling Convertor E3 (ASC-E3) Stirling convertors mounted in an aluminum housing, and Lockheed Martin's Engineering Development Unit (EDU) 4 controller (a fourth-generation controller). The ASC-E3 convertors and Generator Housing Assembly (GHA) closely match the intended ASRG Qualification Unit flight design. A series of tests were conducted to characterize the EU2, its controller, and the convertors in the flight-like GHA. The GHA contained an argon cover gas for these tests. The tests included measurement of convertor, controller, and generator performance and efficiency; quantification of control authority of the controller; disturbance force measurement with varying piston phase and piston amplitude; and measurement of the effect of spacecraft direct current (DC) bus voltage on EU2 performance. The results of these tests are discussed and summarized, providing a basic understanding of EU2 characteristics and the performance and capability of the EDU 4 controller.

  4. Strontium Iodide Instrument Development for Gamma Spectroscopy and Radioisotope Identification

    SciTech Connect

    Beck, P; Cherepy, Nerine; Payne, Stephen A.; Swanberg, E.; Nelson, K.; Thelin, P; Fisher, S E; Hunter, Steve; Wihl, B; Shah, Kanai; Hawrami, Rastgo; Burger, Arnold; Boatner, Lynn A; Momayezi, M; Stevens, K; Randles, M H; Solodovnikov, D

    2014-01-01

    Development of the Europium-doped Strontium Iodide scintillator, SrI2(Eu), has progressed significantly in recent years. SrI2(Eu) has excellent material properties for gamma ray spectroscopy: high light yield (>80,000 ph/MeV), excellent light yield proportionality, and high effective atomic number (Z=49) for high photoelectric cross-section. High quality 1.5 and 2 diameter boules are now available due to rapid advances in SrI2(Eu) crystal growth. In these large SrI2(Eu) crystals, optical self-absorption by Eu2+ degrades the energy resolution as measured by analog electronics, but we mitigate this effect through on-the-fly correction of the scintillation pulses by digital readout electronics. Using this digital correction technique we have demonstrated energy resolution of 2.9% FWHM at 662 keV for a 4 in3 SrI2(Eu) crystal, over 2.6 inches long. Based on this digital readout technology, we have developed a detector prototype with greatly improved radioisotope identification capability compared to Sodium Iodide, NaI(Tl). The higher resolution of SrI2(Eu) yields a factor of 2 to 5 improvement in radioisotope identification (RIID) error rate compared to NaI(Tl).

  5. Industrial radiation and radioisotope gauging techniques and applications

    SciTech Connect

    Gardner, R.P.

    1997-12-01

    The radiation and radioisotope gauging industry in the United States has primarily followed a path of development solely by the private sector. It has remained highly proprietary in nature, which is opposite to the path taken by many other countries. In other countries radiation gauge development has been controlled in large part by government-sponsored research and development, which has spawned many more publications in the open literature. Historically, some of the leaders have been Great Britain, Poland, France, Russia, and Australia. This has possibly led to the misconception that the development of this technology is being dominated by countries outside the United States. This is not a healthy situation-it would be good to see our industry begin to publish more in the open literature and to sponsor more research at universities. In efforts to promote more open-literature publication, the American Nuclear Society (ANS) sponsored a topical meeting on Industrial Radiation and Radioisotope Measurement Applications (IRRMA) in 1988 that was held again in 1992.

  6. Retention of Radium-225 and Its Daughter Radioisotopes in Bone

    SciTech Connect

    Mirzadeh, Saed; Garland, Marc A; Kennel, Steve J

    2008-01-01

    The natural bone seeking tendency of Ra+2, similar to the other alkali metal ions, coupled with the short range high LET of -particle emissions are an ideal combination for localized therapy, and recently 11.4 d 223Ra has been studied for therapy of bone tumors in rats and humans [1,2]. Actinium-225 is also an attractive radioisotope for endo-radiotherapy in a single decay chain from 225Ac, over 26 MeV (~70% of total) is carried by four - particles ranging in energy from 5.7 to 8.4 MeV [3,4]. Although Ac+3 does not home naturally to bone (rather to liver) [5,6], its parent, 225Ra ( -, t1/2 = 15 d), can be used as an in vivo source for 225Ac. A pivotal question for the 225Ra/225Ac in vivo generator system is whether translocation of the daughter nuclei occurs prior to or following the uptake of 225Ra by the bone. In order to assess potential collateral damage to soft tissue organs it is essential to quantitate the extent to which 225Ac is retained in organs following the uptake of 225Ra. We have attempted to answer these questions by investigating the extent of translocation of 225Ac and 213Bi, two daughter radioisotopes of 225Ra, following retention of initially pure 225Ra in bone in normal mice.

  7. Strontium iodide instrument development for gamma spectroscopy and radioisotope identification

    NASA Astrophysics Data System (ADS)

    Beck, P. R.; Cherepy, N. J.; Payne, S. A.; Swanberg, E. L.; Nelson, K. E.; Thelin, P. A.; Fisher, S. E.; Hunter, S.; Wihl, B. M.; Shah, K. S.; Hawrami, R.; Burger, A.; Boatner, L. A.; Momayezi, M.; Stevens, K. T.; Randles, M. H.; Solodovnikov, D.

    2014-09-01

    Development of the Europium-doped Strontium Iodide scintillator, SrI2(Eu2+), has progressed significantly in recent years. SrI2(Eu2+) has excellent material properties for gamma ray spectroscopy: high light yield (<80,000 ph/MeV), excellent light yield proportionality, and high effective atomic number (Z = 49) for high photoelectric cross-section. High quality 1.5" and 2" diameter boules are now available due to rapid advances in SrI2(Eu) crystal growth. In these large SrI2(Eu) crystals, optical self-absorption by Eu2+ degrades the energy resolution as measured by analog electronics, but we mitigate this effect through on-the-fly correction of the scintillation pulses by digital readout electronics. Using this digital correction technique we have demonstrated energy resolution of 2.9% FWHM at 662 keV for a 4 in3 SrI2(Eu) crystal, over 2.6 inches long. Based on this digital readout technology, we have developed a detector prototype with greatly improved radioisotope identification capability compared to Sodium Iodide, NaI(Tl). The higher resolution of SrI2(Eu) yields a factor of 2 to 5 improvement in radioisotope identification (RIID) error rate compared to NaI(Tl).

  8. Radioisotope Thermoelectric Generator Options for Pluto Fast Flyby Mission

    NASA Astrophysics Data System (ADS)

    Schock, Alfred

    1994-07-01

    A small spacecraft design for the Pluto Fast Flyby (PFF) mission is under study by the Jet Propulsion Laboratory (PL) for the National Aeronautics and Space Administration (NASA), for a possible launch as early as 1998. JPL's 1992 baseline design calls for a power source able to furnish an energy output of 3963 kWh and a power output of 69 Watts(e) at the end of the 9.2-year mission. Satisfying those demands is made difficult because NASA management has set a goal of reducing the spacecraft mass from a baseline value of 166 kg to ~110 kg, which implies a mass goal of less than 10 kg for the power source. To support the ongoing NASA/JPL studies, the Department of Energy's Office of Special Applications (DOE/OSA) commissioned Fairchild Space to prepare and analyze conceptual designs of radioisotope power systems for the PFF mission. Thus far, a total of eight options employing essentially the same radioisotope heat source modules were designed and subjected to thermal, electrical, structural, and mass analyses by Fairchild. Five of these - employing thermoelectric converters - are described in the present paper, and three - employing free-piston Stirling converters - are described in the companion paper presented next. The system masses of the thermoelectric options ranged from 19.3 kg to 10.2 kg. In general, the options requiring least development are the heaviest, and the lighter options require more development with greater programmatic risk.

  9. Sodium Variable Conductance Heat Pipe for Radioisotope Stirling Systems

    NASA Technical Reports Server (NTRS)

    Tarau, Calin; Anderson, William G.; Walker, Kara

    2009-01-01

    In a Stirling radioisotope system, heat must continually be removed from the General Purpose Heat Source (GPHS) modules to maintain the modules and surrounding insulation at acceptable temperatures. Normally, the Stirling convertor provides this cooling. If the converter stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS, and also ending the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) has been designed to allow multiple stops and restarts of the Stirling convertor in an Advanced Stirling Radioisotope Generator (ASRG). When the Stirling convertor is turned off, the VCHP will activate when the temperatures rises 30 C above the setpoint temperature. A prototype VCHP with sodium as the working fluid was fabricated and tested in both gravity aided and against gravity conditions for a nominal heater head temperature of 790 C. The results show very good agreement with the predictions and validate the model. The gas front was located at the exit of the reservoir when heater head temperature was 790 C while cooling was ON, simulating an operating Advanced Stirling Converter (ASC). When cooling stopped, the temperature increased by 30 C, allowing the gas front to move past the radiator, which transferred the heat to the case. After resuming the cooling flow, the front returned at the initial location turning OFF the VCHP. The against gravity working conditions showed a colder reservoir and faster transients.

  10. Utilizing Radioisotope Power Systems for Human Lunar Exploration

    NASA Technical Reports Server (NTRS)

    Schreiner, Timothy M.

    2005-01-01

    The Vision for Space Exploration has a goal of sending crewed missions to the lunar surface as early as 2015 and no later than 2020. The use of nuclear power sources could aid in assisting crews in exploring the surface and performing In-Situ Resource Utilization (ISRU) activities. Radioisotope Power Systems (RPS) provide constant sources of electrical power and thermal energy for space applications. RPSs were carried on six of the crewed Apollo missions to power surface science packages, five of which still remain on the lunar surface. Future RPS designs may be able to play a more active role in supporting a long-term human presence. Due to its lower thermal and radiation output, the planned Stirling Radioisotope Generator (SRG) appears particularly attractive for manned applications. The MCNPX particle transport code has been used to model the current SRG design to assess its use in proximity with astronauts operating on the surface. Concepts of mobility and ISRU infrastructure were modeled using MCNPX to analyze the impact of RPSs on crewed mobility systems. Strategies for lowering the radiation dose were studied to determine methods of shielding the crew from the RPSs.

  11. Efficient Radioisotope Energy Transfer by Gold Nanoclusters for Molecular Imaging.

    PubMed

    Volotskova, Olga; Sun, Conroy; Stafford, Jason H; Koh, Ai Leen; Ma, Xiaowei; Cheng, Zhen; Cui, Bianxiao; Pratx, Guillem; Xing, Lei

    2015-08-26

    Beta-emitting isotopes Fluorine-18 and Yttrium-90 are tested for their potential to stimulate gold nanoclusters conjugated with blood serum proteins (AuNCs). AuNCs excited by either medical radioisotope are found to be highly effective ionizing radiation energy transfer mediators, suitable for in vivo optical imaging. AuNCs synthesized with protein templates convert beta-decaying radioisotope energy into tissue-penetrating optical signals between 620 and 800 nm. Optical signals are not detected from AuNCs incubated with Technetium-99m, a pure gamma emitter that is used as a control. Optical emission from AuNCs is not proportional to Cerenkov radiation, indicating that the energy transfer between the radionuclide and AuNC is only partially mediated by Cerenkov photons. A direct Coulombic interaction is proposed as a novel and significant mechanism of energy transfer between decaying radionuclides and AuNCs. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Future planetary missions potentially requiring Radioisotope Power Systems

    NASA Astrophysics Data System (ADS)

    Mondt, Jack F.; Nesmith, Bill J.

    2000-01-01

    This paper summarizes the potential Radioisotope Power System, (RPS), technology requirements for future missions being planned for NASA's Solar System Exploration (SSE) theme. Many missions to the outer planets (Jupiter and beyond) require completion of the work on advanced radioisotope power systems (ARPS) now underway in NASA's Deep Space Systems Technology Program. The power levels for the ARPS can be divided into four classes. Forty to one hundred milliwatt-class provides both thermal and electric power for small in situ science laboratories on the surface of bodies in the solar system. One to two watt class for surface and aerobot science laboratories. Ten to twenty-watt class for micro satellites in orbit, surface science stations and aerobots. One hundred to two hundred watt class for orbiter science spacecraft, for drilling core samples, for powering subsurface hydrobots and cryobots on accessible bodies and for data handling and communicating data from small orbiters, surface laboratories, aerobots and hydrobots back to Earth. Using the most optimistic solar-based power system instead of advanced RPSs pushes the launch masses of these missions beyond the capability of affordable launch vehicles. Advanced RPS is also favored over solar power for obtaining comet samples on extended-duration missions. .

  13. An overview of the Radioisotope Thermoelectric Generator Transportation System Program

    SciTech Connect

    McCoy, J.C.; Becker, D.L.

    1996-03-01

    Radioisotope Thermoelectric Generators (RTG) convert the heat generated by radioactive decay to electricity using thermocouples. RTGs have a long operating life, are reasonably lightweight, and require little or no maintenance once assembled and tested. These factors make RTGs particularly attractive for use in spacecraft. However, because RTGs contain significant quantities of radioactive materials, normally plutonium-238 and its decay products, they must be transported in packages built in accordance with Title 10, Code of Federal Regulations, Part 71. The U.S. Department of Energy assigned the Radioisotope Thermoelectric Generator Transportation System (RTGTS) Program to Westinghouse Hanford Company in 1988 to develop a system meeting the regulatory requirements. The program objective was to develop a transportation system that would fully comply with 10 CFR 71 while protecting RTGs from adverse environmental conditions during normal conditions of transport (e.g., shock and heat). The RTGTS is scheduled for completion in December 1996 and will be available to support the National Aeronautics and Space Administration{close_quote}s Cassini mission to Saturn in October 1997. This paper provides an overview of the RTGTS and discusses the hardware being produced. Additionally, various program management innovations mandated by recent major changes in the U.S. Department of Energy structure and resources will be outlined. {copyright} {ital 1996 American Institute of Physics.}

  14. An overview of the Radioisotope Thermoelectric Generator Transporation System Program

    SciTech Connect

    McCoy, J.C.

    1995-10-01

    Radioisotope Thermoelectric Generators (RTG) convert the heat generated by radioactive decay to electricity using thermocouples. RTGs have a long operating life, are reasonably lightweight, and require little or no maintenance once assembled and tested. These factors make RTGs particularly attractive for use in spacecraft However, because RTGs contain significant quantities of radioactive materials, normally plutonium-238 and its decay products, they must be transported in packages built in accordance with Title 10, Code of Federal Regulations, Part 71. The US Department of Energy assigned the Radioisotope Thermoelectric Generator Transportation System (RTGTS) Program to Westinghouse Hanford Company in 1988 to develop a system meeting the regulatory requirements. The program objective was to develop a transportation system that would fully comply with 10 CFR 71 while protecting RTGs from adverse environmental conditions during normal conditions of transport (e.g., shock and heat). The RTGTS is scheduled for completion in December 1996 and will be available to support the National Aeronautics and Space Administrations Cassini mission to Saturn in October 1997. This paper provides an overview of the RTGTS and discusses the hardware being produced. Additionally, various program management innovations mandated by recent ma or changes in the US Department of Energy structure and resources will be outlined.

  15. The Mars Hopper: a radioisotope powered, impulse driven, long-range, long-lived mobile platform for exploration of Mars

    SciTech Connect

    Steven D. Howe; Robert C. O'Brien; William Taitano; Doug Crawford; Nathan Jerred; Spencer Cooley; John Crapeau; Steve Hansen; Andrew Klein; James Werner

    2011-02-01

    Planetary exploration mission requirements are becoming more demanding. Due to the increasing cost, the missions that provide mobile platforms that can acquire data at multiple locations are becoming more attractive. Wheeled vehicles such as the MER rovers have proven extremely capable but have very limited range and cannot traverse rugged terrain. Flying vehicles such as balloons and airplanes have been proposed but are problematic due to the very thin atmospheric pressure and the strong, dusty winds present on Mars. The Center for Space Nuclear Research has designed an instrumented platform that can acquire detailed data at hundreds of locations during its lifetime - a Mars Hopper. The Mars Hopper concept utilizes energy from radioisotopic decay in a manner different from any existing radioisotopic power sources—as a thermal capacitor. By accumulating the heat from radioisotopic decay for long periods, the power of the source can be dramatically increased for short periods. The platform will be able to "hop" from one location to the next every 5-7 days with a separation of 5-10 km per hop. Preliminary designs show a platform that weighs around 52 kgs unfueled which is the condition at deployment. Consequently, several platforms may be deployed on a single launch from Earth. With sufficient lifetime, the entire surface of Mars can be mapped in detail by a couple dozen platforms. In addition, Hoppers can collect samples from all over the planet, including gorges, mountains and crevasses, and deliver them to a central location for eventual pick-up by a Mars Sample Return mission. The status of the Mars Hopper development project at the CSNR is discussed.

  16. Effect of salinity on the concentrations of radioisotopes in the aquatic environment of a hypersaline coastal lagoon.

    PubMed

    Ramadan, Khaled A; Seddeek, Mostafa K; Sharshar, Taher; Elnimr, Tarek; Badran, Hussein M

    2014-06-01

    Research of the effect of salinity on the fate of radionuclides has been focused on seas or estuarine systems while there is almost no information on marine environments with a salinity higher than that of sea water. The hypersaline Bardawil lagoon is a concentration basin, with evaporation exceeding precipitation. This study presents the characteristics of some environmental factors including salinity and their influence on the distribution of natural and artificial radionuclides in different compartments of the lagoon. The concentrations of (238)U, (234)Th, (228)Ra and (137)Cs in sediments show some degree of dependency on the water's salinity. Migration of these radionuclides in the lagoon's sediments must take place from high salinity to low-salinity regions. Cluster analysis revealed the data structure for sediment by separating (137)Cs and (40)K from (232)Th, (226)Ra, and (234)Th and for sand by separating (40)K from the other radioisotopes.

  17. Evaluation of IAEA Clearance Concept for Low-level Radioactive Waste from a Radioisotope Research Institute.

    PubMed

    Yumoto, Yasuhiro; Okada, Shigeru; Kinno, Ikuo; Nagamatsu, Tomohiro; Nouso, Kazuhiro; Nakayama, Eiichi

    2016-05-01

    The clearance of solid low-level radioactive laboratory waste (LLRW) after decay-in-storage (DIS) obtained from a research institute and thoroughly separated using the separation and classification protocols presented in this study was evaluated. The radioisotope (RI) content of incinerated LLRW from the specified RI research group (group A); the RI content of LLRW obtained in fiscal year 2000, which contained radionuclides with half-lives of less than 164 d (LLRW2); and the RI content of the LLRW reported in group A's disposal records were compared. The LLRW2 and LLRW of group A were incinerated after 2 y of decay-in-storage and immediately after storage, respectively. The highest ratio of the RI of incinerated LLRW to the value in the disposal records was 2.52 for ⁵¹Cr. The radioactivities of radionuclides in both the LLRW2 and LLRW for ³⁵S, ⁴⁵Ca, ⁵¹Cr, ¹²⁵I, ³²P, ³³P, and ⁹⁹mTc and the incinerated ash after 1 y later of decay-in-storage were below the clearance level defined by the RS-G-1.7 of the International Basic Safety Standard without contamination by ³H and ¹⁴C. These remains contained very small amounts of some long-half-life radionuclides of natural origin after 7 y of decay-in-storage. This LLRW separation protocol was effective for the separation of ³H and ¹⁴C. LLRW2 after 2 years of DIS and its incinerated ash after one year later of DIS were below the clearance level for radioactivity and radioactivity concentration.

  18. Space radioisotope power source requirements update and technology status

    SciTech Connect

    Mondt, J.F.

    1998-07-01

    The requirements for a space advanced radioisotope power source are based on potential deep space missions being investigated for the NASA Advanced Space Systems Development Program. Since deep space missions have not been approved, updating requirements is a continuos parallel process of designing the spacecraft and the science instruments to accomplish the potential missions and developing the power source technology to meet changing requirements. There are at least two potential missions, Pluto/Kuiper Express and Europa Orbiter, which may require space advanced radioisotope power sources. The Europa Orbiter has been selected as the preferred first potential mission. However the final decision will depend on the technology readiness of all the subsystems and the project must be able to switch to Pluto Kuiper Express as the first mission as late as the beginning of fiscal year 2000. Therefore the requirements for the power source will cover both potential missions. As the deep space spacecraft design evolves to meet the science requirements and the Alkali Metal Thermal to Electric (AMTEC) technology matures the advanced radioisotope power source design requirements are updated The AMTEC technology developed to date uses stainless steel for the sodium containment material. The higher efficiency required for the space power system dictates that the AMTEC technology must operate at a higher temperature than possible with stainless steel. Therefore refractory materials have been selected as the baseline material for the AMTEC cell. These refractory materials are Nb1Zr for the hot side and Nb1Zr or Nb10Hf1Ti for the cold side. These materials were selected so the AMTEC cell can operate at 1150K to 1350K hot side temperature and 600K to 700K cold side temperature and meet the present power and mass requirements using four to six general purpose heat source modules as the heat source. The new containment materials and brazes will be evaluated as to lifetime

  19. Stirling Convertor Technologies Being Developed for a Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Thieme, Lanny G.

    2003-01-01

    The Department of Energy, Lockheed Martin, Stirling Technology Company (STC), and the NASA Glenn Research Center are developing a high-efficiency Stirling Radioisotope Generator (SRG) for NASA space science missions. The SRG is being developed for multimission use, including providing electric power for unmanned Mars rovers and deep space missions. On Mars, rovers with SRGs would be used for missions that might not be able to use photovoltaic power systems, such as exploration at high Martian latitudes and missions of long duration. The projected SRG system efficiency of 23 percent will reduce the required amount of radioisotope by a factor of 4 or more in comparison to currently used Radioisotope Thermoelectric Generators. The Department of Energy recently named Lockheed Martin as the system integration contractor. Lockheed Martin has begun to develop the SRG engineering unit under contract to the Department of Energy, and has contract options to develop the qualification unit and the first flight units. The developers expect the SRG to produce about 114 Wdc at the beginning of mission, using two opposed Stirling convertors and two General Purpose Heat Source modules. STC previously developed the Stirling convertor under contract to the Department of Energy and is now providing further development as a subcontractor to Lockheed Martin. Glenn is conducting an in-house technology project to assist in developing the convertor for space qualification and mission implementation. A key milestone was recently reached with the accumulation of 12 000 hr of long-term aging on two types of neodymium-iron boron permanent magnets. These tests are characterizing any possible aging in the strength or demagnetization resistance of the magnets used in the linear alternator. Preparations are underway for a thermal/vacuum system demonstration and unattended operation during endurance testing of the 55-We Technology Demonstration Convertors. In addition, Glenn is developing a

  20. Utilizing Radioisotope Power System Waste Heat for Spacecraft Thermal Management

    NASA Technical Reports Server (NTRS)

    Pantano, David R.; Dottore, Frank; Tobery, E. Wayne; Geng, Steven M.; Schreiber, Jeffrey G.; Palko, Joseph L.

    2005-01-01

    An advantage of using a Radioisotope Power System (RPS) for deep space or planetary surface missions is the readily available waste heat, which can be used for a number of beneficial purposes including: maintaining electronic components within a controlled temperature range, warming propulsion tanks and mobility actuators, and maintaining liquid propellants above their freezing temperature. Previous missions using Radioisotope Thermoelectric Generators (RTGs) dissipated large quantities of waste heat due to the low efficiency of the thermoelectric conversion technology. The next generation RPSs, such as the 110-Watt Stirling Radioisotope Generator (SRG110) will have higher conversion efficiencies, thereby rejecting less waste heat at a lower temperature and may require alternate approaches to transferring waste heat to the spacecraft. RTGs, with efficiencies of 6 to 7 percent, reject their waste heat at the relatively high heat rejection temperature of 200 C. This is an advantage when rejecting heat to space; however, transferring heat to the internal spacecraft components requires a large and heavy radiator heat exchanger. At the same time, sensitive spacecraft instruments must be shielded from the thermal radiation of the RTG. The SRG110, with an efficiency around 22 percent and 50 C nominal housing surface temperature, can readily transfer the available waste heat directly via heat pipes, thermal straps, or fluid loops. The lower temperatures associated with the SRG110 avoid the chances of overheating other scientific components, eliminating the need for thermal shields. This provides the spacecraft designers more flexibility when locating the generator for a specific mission. A common misconception with high-efficiency systems is that there is not enough waste heat for spacecraft thermal management. This paper will dispel this misconception and investigate the use of a high-efficiency SRG110 for spacecraft thermal management and outline potential methods of

  1. RTGs - The powering of Ulysses. [Radio-isotope Thermoelectric Generator

    NASA Technical Reports Server (NTRS)

    Mastal, E. F.; Campbell, R. W.

    1990-01-01

    The radio-isotope thermoelectric generator (RTG) for Ulysses' electronic supply is described noting that lack of sufficient sunlight renders usual solar cell power generation ineffective due to increased distance from sun. The history of the RTG in the U.S.A. is reviewed citing the first RTG launch in 1961 with an electrical output of 2.7 W and the improved Ulysses RTG, which provides 285 W at mission beginning and 250 W at mission end. The RTG concept is discussed including the most recent RTG technology developed by the DOE, the General Purpose Heat Source RTG (GPHS-RTG). The system relies upon heat generated by radioactive decay using radioactive plutonium-238, which is converted directly to energy using the Seebeck method.

  2. Radioisotope cisternography in acute viral encephalitis. A reappraisal

    SciTech Connect

    Fukuyama, H.; Kawamura, J.

    1982-05-01

    Five cases of presumed acute viral encephalitis with convulsions were examined with radioisotope (RI) cisternography six and 24 hours after an intrathecal injection of 1 mCi of pentetic acid labeled with either /sup 169/Yb or /sup 111/In. All cases showed abnormalities with this study. The cold areas observed with RI cisternography were well correlated with abnormal foci on the EEG. Although the findings are nonspecific, the CSF dynamics and patency of the subarachnoid space are easily examined by RI cisternography without appreciable complications. It is a useful supplementary diagnostic method to depict the extent of lobar abnormalities of cerebral cortex, particularly at an early stage, that either narrow or obliterate subarachnoid space and CSF pathways.

  3. AMTEC radioisotope power system for the Pluto Express mission

    SciTech Connect

    Ivanenok, J.F. III; Sievers, R.K.

    1995-12-31

    The Alkali Metal Thermal to Electric Converter (AMTEC) technology has made substantial advances in the last 3 years through design improvements and technical innovations. In 1993 programs began to produce an AMTEC cell specifically for the NASA Pluto Express Mission. A set of efficiency goals was established for this series of cells to be developed. According to this plan, cell {number_sign}8 would be 17% efficient but was actually 18% efficient. Achieving this goal, as well as design advances that allow the cell to be compact, has resulted in pushing the cell from an unexciting 2 W/kg and 2% efficiency to very attractive 40 W/kg and 18% measured efficiency. This paper will describe the design and predict the performance of a radioisotope powered AMTEC system for the Pluto Express mission.

  4. Testing to Characterize the Advanced Stirling Radioisotope Generator Engineering Unit

    NASA Technical Reports Server (NTRS)

    Lewandowski, Edward; Schreiber, Jeffrey

    2010-01-01

    The Advanced Stirling Radioisotope Generator (ASRG), a high efficiency generator, is being considered for space missions. Lockheed Martin designed and fabricated an engineering unit (EU), the ASRG EU, under contract to the Department of Energy. This unit is currently undergoing extended operation testing at the NASA Glenn Research Center to generate performance data and validate life and reliability predictions for the generator and the Stirling convertors. It has also undergone performance tests to characterize generator operation while varying control parameters and system inputs. This paper summarizes and explains test results in the context of designing operating strategies for the generator during a space mission and notes expected differences between the EU performance and future generators.

  5. Development and Buildup of a Stirling Radioisotope Generator Electrical Simulator

    NASA Technical Reports Server (NTRS)

    Prokop, Norman F.; Krasowski, Michael J.; Greer, Lawrence C.; Flatico, Joseph M.; Spina, Dan C.

    2008-01-01

    This paper describes the development of a Stirling Radioisotope Generator (SRG) Simulator for use in a prototype lunar robotic rover. The SRG developed at NASA Glenn Research Center (GRC) is a promising power source for the robotic exploration of the sunless areas of the moon. The simulator designed provides a power output similar to the SRG output of 5.7 A at 28 Vdc, while using ac wall power as the input power source. The designed electrical simulator provides rover developers the physical and electrical constraints of the SRG supporting parallel development of the SRG and rover. Parallel development allows the rover design team to embrace the SRG s unique constraints while development of the SRG is continued to a flight qualified version.

  6. End-on radioisotope thermoelectric generator impact tests

    SciTech Connect

    Reimus, M.A.H.; Hhinckley, J.E.

    1997-01-01

    The General-Purpose Heat Source (GPHS) provides power for space missions by transmitting the heat of [sup 238]Pu decay to an array of thermoelectric elements in a radioisotope thermoelectric generator (RTG). The modular GPHS design was developed to address both survivability during launch abort and return from orbit. The first two RTG Impact Tests were designed to provide information on the response of a fully loaded RTG to end-on impact against a concrete target. The results of these tests indicated that at impact velocities up to 57 m/s the converter shell and internal components protect the GPHS capsules from excessive deformation. At higher velocities, some of the internal components of the RTG interact with the GPHS capsules to cause excessive localized deformation and failure.

  7. Computer program for the transient analysis of radioisotope thermoelectric generators.

    NASA Technical Reports Server (NTRS)

    Eggers, P. E.; Ridihalgh, J. L.

    1972-01-01

    A computer program is described which represents a comprehensive analytical tool providing the capability for predicting the output power and temperature profile of an arbitrary radioisotope thermoelectric generator (RTG) design in the presence of time-dependent operating conditions. The approach taken involves the merging of three existing computer programs - namely, an RTG weight optimization design program, a thermoelectric analysis program, and a nodal heat-transfer computer program. A total of seven transient conditions are included in the computer program as the principal transients affecting long- and short-term performance characteristics of RTGs. This computer program is unique in that it designs an optimum RTG, generates a thermal model or analog and performs heat-transfer analysis of the RTG under user-specified transient conditions.

  8. Radioisotope thermoelectric generator/thin fragment impact test

    SciTech Connect

    Reimus, M.A.H.; Hinckley, J.E.

    1998-12-31

    The General-Purpose Heat Source (GPHS) provides power for space missions by transmitting the heat of {sup 238}Pu decay to an array of thermoelectric elements in a radioisotope thermoelectric generator (RTG). Because the potential for a launch abort or return from orbit exists for any space mission, the heat source response to credible accident scenarios is being evaluated. This test was designed to provide information on the response of a loaded RTG to impact by a fragment similar to the type of fragment produced by breakup of the spacecraft propulsion module system (PMS). The results of this test indicated that impact of the RTG by a thin aluminum fragment traveling at 306 m/s may result in significant damage to the convertor housing, failure of one fueled clad, and release of a small quantity of fuel.

  9. Multimodality Therapy: Bone-Targeted Radioisotope Therapy of Prostate Cancer

    PubMed Central

    Tu, Shi-Ming; Lin, Sue-Hwa; Podoloff, Donald A.; Logothetis, Christopher J.

    2016-01-01

    Accumulating data suggest that bone-seeking radiopharmaceuticals can be used to treat prostate cancer bone metastasis and improve the clinical outcome of patients with advanced prostate cancer. It remains to be elucidated whether radiopharmaceuticals enhance the disruption of the onco-niche or the eradication of micrometastatic cells in the bone marrow. The purpose of this review is to investigate the role of bone-targeted radioisotope therapy in the setting of multimodality therapy for advanced prostate cancer. We examine available data and evaluate whether dose escalation, newer generations, or repeated dosing of radiopharmaceuticals enhance their antitumor effects and whether their combination with hormone ablative therapy, chemotherapy, or novel targeted therapy can improve clinical efficacy. PMID:20551894

  10. Fabrication of light weight radioisotope heater unit hardware components

    SciTech Connect

    McNeil, D.C.

    1996-03-01

    The Light Weight Radioisotope Heater Unit (LWRHU) is planned to be used on the National Aeronautics and Space Administration (NASA) Cassini Mission, to provide localized thermal energy as strategic locations on the spacecraft. These one watt heater units will support the operation of many on-board instruments that require a specific temperature range to function properly. The system incorporates a fuel pellet encapsulated in a vented metallic clad fabricated from platinum-30{percent} rhodium (Pt-30{percent}Rh) tubing, sheet and foil materials. To complete the package, the clad assemblies are placed inside a combination of graphite components. This report describes the techniques employed by Mound related to the fabrication and sub assembly processes of the LWRHU clad hardware components. Included are details concerning configuration control systems, material procurement and certification, hardware fabrication specifics, and special processes that are utilized. {copyright} {ital 1996 American Institute of Physics.}

  11. Radioisotope thermoelectric generator/thin fragment impact test

    SciTech Connect

    Reimus, M.A.; Hinckley, J.E.

    1998-01-01

    The General-Purpose Heat Source (GPHS) provides power for space missions by transmitting the heat of {sup 238}Pu decay to an array of thermoelectric elements in a radioisotope thermoelectric generator (RTG). Because the potential for a launch abort or return from orbit exists for any space mission, the heat source response to credible accident scenarios is being evaluated. This test was designed to provide information on the response of a loaded RTG to impact by a fragment similar to the type of fragment produced by breakup of the spacecraft propulsion module system (PMS). The results of this test indicated that impact of the RTG by a thin aluminum fragment traveling at 306 m/s may result in significant damage to the converter housing, failure of one fueled clad, and release of a small quantity of fuel. {copyright} {ital 1998 American Institute of Physics.}

  12. Radioisotope thermoelectric generator/thin fragment impact test

    SciTech Connect

    Reimus, M. A. H.; Hinckley, J. E.

    1998-01-15

    The General-Purpose Heat Source (GPHS) provides power for space missions by transmitting the heat of {sup 238}Pu decay to an array of thermoelectric elements in a radioisotope thermoelectric generator (RTG). Because the potential for a launch abort or return from orbit exists for any space mission, the heat source response to credible accident scenarios is being evaluated. This test was designed to provide information on the response of a loaded RTG to impact by a fragment similar to the type of fragment produced by breakup of the spacecraft propulsion module system (PMS). The results of this test indicated that impact of the RTG by a thin aluminum fragment traveling at 306 m/s may result in significant damage to the converter housing, failure of one fueled clad, and release of a small quantity of fuel.

  13. Particle-beam accelerators for radiotherapy and radioisotopes

    NASA Astrophysics Data System (ADS)

    Boyd, T. J., Jr.; Crandall, K. R.; Hamm, R. W.; Hansborough, L. D.; Hoeberling, R. F.; Jameson, R. A.; Knapp, E. A.; Mueller, D. W.; Potter, J. M.; Stokes, R. H.

    The philosophy used in developing the PIGMI (pion generator for medical irradiation) technology was that the parameters chosen for physics research machines are not necessarily the right ones for a dedicated therapy or radioisotope machine. In particular, the beam current and energy can be optimized, and the design should emphasize minimum size, simplicity and reliability of operation, and economy in capital and operating costs. A major part of achieving these goals lay in raising the operating frequency and voltage gradient of the accelerator, which shrinks the diameter and length of the components. Several other technical innovations resulted in major system improvements. One of these is a radically new type of accelerator structure named the radio frequency quadrupole accelerator. This allowed the elimination of the large, complicated ion source used in previous ion accelerators, and a very high quality accelerated beam. Also, by using advanced permanent magnet materials to make the focusing elements, the system becomes much simpler. Other improvements are described.

  14. Reliability Demonstration Approach for Advanced Stirling Radioisotope Generator

    NASA Technical Reports Server (NTRS)

    Ha, CHuong; Zampino, Edward; Penswick, Barry; Spronz, Michael

    2010-01-01

    Developed for future space missions as a high-efficiency power system, the Advanced Stirling Radioisotope Generator (ASRG) has a design life requirement of 14 yr in space following a potential storage of 3 yr after fueling. In general, the demonstration of long-life dynamic systems remains difficult in part due to the perception that the wearout of moving parts cannot be minimized, and associated failures are unpredictable. This paper shows a combination of systematic analytical methods, extensive experience gained from technology development, and well-planned tests can be used to ensure a high level reliability of ASRG. With this approach, all potential risks from each life phase of the system are evaluated and the mitigation adequately addressed. This paper also provides a summary of important test results obtained to date for ASRG and the planned effort for system-level extended operation.

  15. A Pixelated Emission Detector for RadiOisotopes (PEDRO)

    NASA Astrophysics Data System (ADS)

    Dimmock, M. R.; Gillam, J. E.; Beveridge, T. E.; Brown, J. M. C.; Lewis, R. A.; Hall, C. J.

    2009-12-01

    The Pixelated Emission Detector for RadiOisotopes (PEDRO) is a hybrid imager designed for the measurement of single photon emission from small animals. The proof-of-principle device currently under development consists of a Compton-camera situated behind a mechanical modulator. The combination of mechanical and electronic (hybrid) collimation should provide optimal detection characteristics over a broad spectral range (30 keV≤Eγ≤511 keV), through a reduction in the sensitivity-resolution trade-off, inherent in conventional mechanically collimated configurations. This paper presents GEANT4 simulation results from the PEDRO geometry operated only as a Compton camera in order to gauge its advantage when used in concert with mechanical collimation—regardless of the collimation pattern. The optimization of multiple detector spacing and resolution parameters is performed utilizing the Median Distance of Closest Approach (MDCA) and has been shown to result in an optimum distance, beyond which only a loss in sensitivity occurs.

  16. Analysis of a case of internal contamination with cobalt radioisotopes.

    PubMed

    Vrba, T; Malatova, I; Jurochova, B

    2007-01-01

    Internal contamination by compounds of cobalt radioisotopes occurs time to time at nuclear power plants. Intakes and committed effective doses are estimated by biokinetic models described in ICRP publications. The paper deals with a case of internal contamination of a worker engaged in a maintenance task at NPP Dukovany. In this case significant discrepancy was observed between intakes based on various datasets (whole body counting, analysis of urine and faeces) when default model setting was used. The reason of this phenomenon was searched for. Three different least square methods of fits were used to find out possible effect of a fitting method. The measured data were fitted by set of biokinetic functions, which covered all intake ways (ingestion and inhalation) and types (M, S, different AMADs and different f1) of the contaminant. The biokinetic model of cobalt needs further improvements as to find better agreement between data fit from direct measurements and bioassay.

  17. Pathway of radioisotopes from land surface to sewage sludge

    NASA Astrophysics Data System (ADS)

    Fischer, Helmut W.; Yokoo, Yoshiyuki

    2014-05-01

    Radioactive surface contaminations will only partially remain at the original location - a fraction of the inventory will take part in (mainly terrestrial and aquatic) environmental transport processes. The probably best known and most important process comprises the food chain. Besides, the translocation of dissolved and particle-bound radioisotopes with surface waters plays an important role. These processes can have the effect of displacing large radioisotope amounts over considerable distances and of creating new sinks and hot spots, as it is already known for sewage sludge. We are reporting on a combined modeling and experimental project concerning the transport of I-131 and Cs-134/Cs-137 FDNPP 2011 depositions in the Fukushima Prefecture. Well-documented experimental data sets are available for surface deposition and sewage sludge concentrations. The goal is to model the pathway in between, involving surface runoff, transport in the sewer system and processes in the sewage treatment plant. Watershed runoff and sewer transport will be treated with models developed recently by us in other projects. For sewage treatment processes a new model is currently being constructed. For comparison and further validation, historical data from Chernobyl depositions and tracer data from natural and artificial, e.g. medical, isotopes will be used. First results for 2011 data from Fukushima Prefecture will be presented. The benefits of the study are expected to be two-fold: on one hand, the abundant recent and historical data will help to develop and improve environmental transport models; on the other hand, both data and models will help in identifying the most critical points in the envisaged transport pathways in terms of radiation protection and waste management.

  18. Advanced Stirling Convertor Development for NASA Radioisotope Power Systems

    NASA Technical Reports Server (NTRS)

    Wong, Wayne A.; Wilson, Scott D.; Collins, Josh

    2015-01-01

    Sunpower Inc.'s Advanced Stirling Convertor (ASC) initiated development under contract to the NASA Glenn Research Center and after a series of successful demonstrations, the ASC began transitioning from a technology development project to a flight development project. The ASC has very high power conversion efficiency making it attractive for future Radioisotope Power Systems (RPS) in order to make best use of the low plutonium-238 fuel inventory in the United States. In recent years, the ASC became part of the NASA and Department of Energy (DOE) Advanced Stirling Radioisotope Generator (ASRG) Integrated Project. Sunpower held two parallel contracts to produce ASCs, one with the DOE and Lockheed Martin to produce the ASC-F flight convertors, and one with NASA Glenn for the production of ASC-E3 engineering units, the initial units of which served as production pathfinders. The integrated ASC technical team successfully overcame various technical challenges that led to the completion and delivery of the first two pairs of flightlike ASC-E3 by 2013. However, in late fall 2013, the DOE initiated termination of the Lockheed Martin ASRG flight development contract driven primarily by budget constraints. NASA continues to recognize the importance of high-efficiency ASC power conversion for RPS and continues investment in the technology including the continuation of ASC-E3 production at Sunpower and the assembly of the ASRG Engineering Unit #2. This paper provides a summary of ASC technical accomplishments, overview of tests at Glenn, plans for continued ASC production at Sunpower, and status of Stirling technology development.

  19. Radioisotope synoviorthesis with Holmium-166-chitosan complex in haemophilic arthropathy.

    PubMed

    Cho, Y J; Kim, K I; Chun, Y S; Rhyu, K H; Kwon, B K; Kim, D Y; Yoo, M C

    2010-07-01

    Radiosynoviorthesis is a safe and easy method for synovectomy in haemophilic arthropathy. Various agents have been used in radiosynoviorthesis, especially newly developed agent Holmium-166-chitosan complex has good clinical outcome. This study analysed clinical results and radiologic evaluation of radioisotope synoviorthesis using Holmium-166-chitosan complex in haemophilic arthropathy. From March 2001 to December 2003, 58 radiosynoviorthesis were performed in 53 haemophiliacs. The average age at procedure was 13.8 years. The Arnold and Hilgartner stage of the patients was from I to IV. Holmium-166-chitosan complex was injected in 31 ankle joints, 19 elbow joints and 8 knee joints. Average follow-up was 33 months since primary procedure. The range of motion of each joint, frequency of intra-articular bleeding and factor dose used were analysed for clinical assessment. There was no significant improvement of range of motion in affected joints. After procedure, the average frequency of bleeding of the elbow joint has decreased from 3.76 to 0.47 times per month, the knee joint from 5.87 to 1.12 times per month, and the ankle joint from 3.62 to 0.73 times per month respectively (P < 0.05). After treatment, the average coagulation factor dose injected was significantly decreased to 779.3 units per month from 2814.8 units per month before treatment (P < 0.001). Radioisotope synoviorthesis with Holmium-166-chitosan complex in haemophilic arthropathy is a very safe and simple procedure with the expectation of a satisfactory outcome without serious complication. It has excellent bleeding control effect on target joint and the need for substitution of coagulation factor concentrate can be reduced.

  20. High Temperature Variable Conductance Heat Pipes for Radioisotope Stirling Systems

    SciTech Connect

    Tarau, Calin; Walker, Kara L.; Anderson, William G.

    2009-03-16

    In a Stirling radioisotope system, heat must continually be removed from the GPHS modules, to maintain the GPHS modules and surrounding insulation at acceptable temperatures. Normally, the Stirling converter provides this cooling. If the Stirling engine stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS, but also ending the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) is under development to allow multiple stops and restarts of the Stirling engine. The status of the ongoing effort in developing this technology is presented in this paper. An earlier, preliminary design had a radiator outside the Advanced Stirling Radioisotope Generator (ASRG) casing, used NaK as the working fluid, and had the reservoir located on the cold side adapter flange. The revised design has an internal radiator inside the casing, with the reservoir embedded inside the insulation. A large set of advantages are offered by this new design. In addition to reducing the overall size and mass of the VCHP, simplicity, compactness and easiness in assembling the VCHP with the ASRG are significantly enhanced. Also, the permanently elevated temperatures of the entire VCHP allows the change of the working fluid from a binary compound (NaK) to single compound (Na). The latter, by its properties, allows higher performance and further mass reduction of the system. Preliminary design and analysis shows an acceptable peak temperature of the ASRG case of 140 deg. C while the heat losses caused by the addition of the VCHP are 1.8 W.

  1. INTRACORPOREAL HEAT DISSIPATION FROM A RADIOISOTOPE-POWERED ARTIFICIAL HEART

    PubMed Central

    Huffman, Fred N.; Hagen, Kenneth G.; Whalen, Robert L.; Fuqua, John M.; Norman, John C.

    1974-01-01

    The feasibility of radioisotope-fueled circulatory support systems depends on the ability of the body to dissipate the reject heat from the power source driving the blood pump as well as to tolerate chronic intracorporeal radiation. Our studies have focused on the use of the circulating blood as a heat sink. Initial in vivo heat transfer studies utilized straight tube heat exchangers (electrically and radioisotope energized) to replace a segment of the descending aorta. More recent studies have used a left ventricular assist pump as a blood-cooled heat exchanger. This approach minimizes trauma, does not increase the area of prosthetic interface with the blood, and minimizes system volume. Heat rejected from the thermal engine (vapor or gas cycle) is transported from the nuclear power source in the abdomen to the pump in the thoracic cavity via hydraulic lines. Adjacent tissue is protected from the fuel capsule temperature (900 to 1200°F) by vacuum foil insulation and polyurethane foam. The in vivo thermal management problems have been studied using a simulated thermal system (STS) which approximates the heat rejection and thermal transport mechanisms of the nuclear circulatory support systems under development by NHLI. Electric heaters simulate the reject heat from the thermal engines. These studies have been essential in establishing the location, suspension, surgical procedures, and postoperative care for implanting prototype nuclear heart assist systems in calves. The pump has a thermal impedance of 0.12°C/watt. Analysis of the STS data in terms of an electrical analog model implies a heat transfer coefficient of 4.7 × 10−3 watt/cm2°C in the abdomen compared to a value of 14.9 × 10−3 watt/cm2°C from the heat exchanger plenum into the diaphragm. Images PMID:15215968

  2. Radio-isotope production scale-up at the University of Wisconsin

    SciTech Connect

    Nickles, Robert Jerome

    2014-06-19

    Our intent has been to scale up our production capacity for a subset of the NSAC-I list of radioisotopes in jeopardy, so as to make a significant impact on the projected national needs for Cu-64, Zr-89, Y-86, Ga-66, Br-76, I-124 and other radioisotopes that offer promise as PET synthons. The work-flow and milestones in this project have been compressed into a single year (Aug 1, 2012- July 31, 2013). The grant budget was virtually dominated by the purchase of a pair of dual-mini-cells that have made the scale-up possible, now permitting the Curie-level processing of Cu-64 and Zr-89 with greatly reduced radiation exposure. Mile stones: 1. We doubled our production of Cu-64 and Zr-89 during the grant period, both for local use and out-bound distribution to ≈ 30 labs nationwide. This involved the dove-tailing of beam schedules of both our PETtrace and legacy RDS cyclotron. 2. Implemented improved chemical separation of Zr-89, Ga-66, Y-86 and Sc-44, with remote, semi-automated dissolution, trap-and-release separation under LabView control in the two dual-mini-cells provided by this DOE grant. A key advance was to fit the chemical stream with miniature radiation detectors to confirm the transfer operations. 3. Implemented improved shipping of radioisotopes (Cu-64, Zr-89, Tc-95m, and Ho-163) with approved DOT 7A boxes, with a much-improved FedEx shipping success compared to our previous steel drums. 4. Implemented broad range quantitative trace metal analysis, employing a new microwave plasma atomic emission spectrometer (Agilent 4200) capable of ppb sensitivity across the periodic table. This new instrument will prove essential in bringing our radiometals into FDA compliance needing CoA’s for translational research in clinical trials. 5. Expanded our capabilities in target fabrication, with the purchase of a programmable 1600 oC inert gas tube furnace for the smelting of binary alloy target materials. A similar effort makes use of our RF induction furnace, allowing

  3. An Overview and Status of NASA's Radioisotope Power Conversion Technology NRA

    NASA Technical Reports Server (NTRS)

    Anderson, David J.; Wong, Wayne A.; Tuttle, Karen L.

    2005-01-01

    NASA's Advanced Radioisotope Power Systems (RPS) development program is developing next generation radioisotope power conversion technologies that will enable future missions that have requirements that can not be met by either photovoltaic systems or by current Radioisotope Power System (RPS) technology. The Advanced Power Conversion Research and Technology project of the Advanced RPS development program is funding research and technology activities through the NASA Research Announcement (NRA) 02-OSS-01, "Research Opportunities in Space Science 2002" entitled "Radioisotope Power Conversion Technology" (RPCT), August 13, 2002. The objective of the RPCT NRA is to advance the development of radioisotope power conversion technologies to provide significant improvements over the state-of-practice General Purpose Heat Source/Radioisotope Thermoelectric Generator by providing significantly higher efficiency to reduce the number of radioisotope fuel modules, and increase specific power (watts/kilogram). Other Advanced RPS goals include safety, long-life, reliability, scalability, multi-mission capability, resistance to radiation, and minimal interference with the scientific payload. Ten RPCT NRA contracts were awarded in 2003 in the areas of Brayton, Stirling, thermoelectric (TE), and thermophotovoltaic (TPV) power conversion technologies. This paper will provide an overview of the RPCT NRA, and a brief summary of accomplishments over the first 18 months but focusing on advancements made over the last 6 months.

  4. Characterization of front-end electronics for CZT based handheld radioisotope identifier

    SciTech Connect

    Lombigit, L.; Rahman, Nur Aira Abd; Mohamad, Glam Hadzir Patai; Ibrahim, Maslina Mohd; Yussup, Nolida; Yazid, Khairiah; Jaafar, Zainudin

    2016-01-22

    A radioisotope identifier device based on large volume Co-planar grid CZT detector is current under development at Malaysian Nuclear Agency. This device is planned to be used for in-situ identification of radioisotopes based on their unique energies. This work reports on electronics testing performed on the front-end electronics (FEE) analog section comprising charge sensitive preamplifier-pulse shaping amplifier chain. This test involves measurement of charge sensitivity, pulse parameters and electronics noise. This report also present some preliminary results on the spectral measurement obtained from gamma emitting radioisotopes.

  5. Radioisotope electric propulsion of sciencecraft to the outer solar system and near-interstellar space

    SciTech Connect

    Noble, R.J.

    1998-08-01

    Recent results are presented in the study of radioisotope electric propulsion as a near-term technology for sending small robotic sciencecraft to the outer Solar System and near-interstellar space. Radioisotope electric propulsion (REP) systems are low-thrust, ion propulsion units based on radioisotope electric generators and ion thrusters. Powerplant specific masses are expected to be in the range of 100 to 200 kg/kW of thrust power. Planetary rendezvous missions to Pluto, fast missions to the heliopause (100 AU) with the capability to decelerate an orbiter for an extended science program and prestellar missions to the first gravitational lens focus of the Sun (550 AU) are investigated.

  6. An in-cell alpha detection system for radioisotope component assembly operations

    SciTech Connect

    Carteret, B.A. ); Goles, R.W. )

    1991-09-01

    A remotely operated alpha detection system is being developed for use at the Radioisotope Power Systems Facility at the US Department of Energy's Hanford Site. It will be used in hot cells being constructed to assemble components of Radioisotope Thermoelectric Generators for space power applications. The in-cell detection equipment will survey radiological swipe samples to determine smearable surface contamination levels on radioisotope fuel, fueled components, and hot-cell work areas. This system is potentially adaptable to other hot cell and glovebox applications where radiation dose rates and contamination levels are expected to be low. 2 figs.

  7. Characterization of front-end electronics for CZT based handheld radioisotope identifier

    NASA Astrophysics Data System (ADS)

    Lombigit, L.; Rahman, Nur Aira Abd; Mohamad, Glam Hadzir Patai; Ibrahim, Maslina Mohd; Yussup, Nolida; Yazid, Khairiah; Jaafar, Zainudin

    2016-01-01

    A radioisotope identifier device based on large volume Co-planar grid CZT detector is current under development at Malaysian Nuclear Agency. This device is planned to be used for in-situ identification of radioisotopes based on their unique energies. This work reports on electronics testing performed on the front-end electronics (FEE) analog section comprising charge sensitive preamplifier-pulse shaping amplifier chain. This test involves measurement of charge sensitivity, pulse parameters and electronics noise. This report also present some preliminary results on the spectral measurement obtained from gamma emitting radioisotopes.

  8. Radioisotope generators for short-lived positron emitters applicable to positron emission tomography

    NASA Astrophysics Data System (ADS)

    Yano, Y.

    1989-04-01

    Radioisotope generators provide short-lived positron emitters for positron emission tomography (PET) without the need for an on-site cyclotron. These generators consist of a long-lived parent radionuclide, generally produced on an accelerator, from which the short-lived daughter radionuclide is separated and used as needed. Generators developed and applied to PET studies include 288 d 68Ge for 68 min 68Ga, 25 d 82Sr for 76 s 82Rb and 20.1 h 122Xe for 3.6 min 122I. These radiotracers have been used for the assessment of myocardial and brain blood flow in patient studies. Additionally, 82Rb has been used to determine the breakdown in the blood brain barrier in brain tumor patients who have undergone radiation therapy. When used in conjunction with 18F-fluorodeoxylucose produced on a regional cyclotron for the measurement of glucose utilization in brain tumors, differential diagnosis can be made between tumor regrowth and radiation therapy necrosis. Other possible applications include the detection of vascular lesions with 68Ga labeled platelets or porphyrins.

  9. Radioisotope Stirling Engine Powered Airship for Atmospheric and Surface Exploration of Titan

    NASA Technical Reports Server (NTRS)

    Colozza, Anthony J.; Cataldo, Robert L.

    2014-01-01

    The feasibility of an advanced Stirling radioisotope generator (ASRG) powered airship for the near surface exploration of Titan was evaluated. The analysis did not consider the complete mission only the operation of the airship within the atmosphere of Titan. The baseline airship utilized two ASRG systems with a total of four general-purpose heat source (GPHS) blocks. Hydrogen gas was used to provide lift. The ASRG systems, airship electronics and controls and the science payload were contained in a payload enclosure. This enclosure was separated into two sections, one for the ASRG systems and the other for the electronics and payload. Each section operated at atmospheric pressure but at different temperatures. The propulsion system consisted of an electric motor driving a propeller. An analysis was set up to size the airship that could operate near the surface of Titan based on the available power from the ASRGs. The atmospheric conditions on Titan were modeled and used in the analysis. The analysis was an iterative process between sizing the airship to carry a specified payload and the power required to operate the electronics, payload and cooling system as well as provide power to the propulsion system to overcome the drag on the airship. A baseline configuration was determined that could meet the power requirements and operate near the Titan surface. From this baseline design additional trades were made to see how other factors affected the design such as the flight altitude and payload mass and volume.

  10. Radioisotope Electric Propulsion (REP): A Near-Term Approach to Nuclear Propulsion

    NASA Technical Reports Server (NTRS)

    Schmidt, George R.; Manzella, David H.; Kamhawi, Hani; Kremic, Tibor; Oleson, Steven R.; Dankanich, John W.; Dudzinski, Leonard A.

    2009-01-01

    Studies over the last decade have shown radioisotope-based nuclear electric propulsion to be enhancing and, in some cases, enabling for many potential robotic science missions. Also known as radioisotope electric propulsion (REP), the technology offers the performance advantages of traditional reactor-powered electric propulsion (i.e., high specific impulse propulsion at large distances from the Sun), but with much smaller, affordable spacecraft. Future use of REP requires development of radioisotope power sources with system specific powers well above that of current systems. The US Department of Energy and NASA have developed an advanced Stirling radioisotope generator (ASRG) engineering unit, which was subjected to rigorous flight qualification-level tests in 2008, and began extended lifetime testing later that year. This advancement, along with recent work on small ion thrusters and life extension technology for Hall thrusters, could enable missions using REP sometime during the next decade.

  11. 77 FR 21592 - Guidelines for Preparing and Reviewing Licensing Applications for the Production of Radioisotopes

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-10

    ... Chapters 7-18 of Draft Interim Staff Guidance (ISG) NPR-ISG-2011-002, augmenting NUREG-1537, Part 1...,'' for the production of radioisotopes. The ISG augmenting NUREG-1537, Parts 1 & 2, Chapters 1-6...

  12. Estimates for production of radioisotopes of medical interest at Extreme Light Infrastructure - Nuclear Physics facility

    NASA Astrophysics Data System (ADS)

    Luo, Wen; Bobeica, Mariana; Gheorghe, Ioana; Filipescu, Dan M.; Niculae, Dana; Balabanski, Dimiter L.

    2016-01-01

    We report Monte Carlo simulations of the production of radioisotopes of medical interest through photoneutron reactions using the high-brilliance γ-beam of the Extreme Light Infrastructure - Nuclear Physics (ELI-NP) facility. The specific activity for three benchmark radioisotopes, 99Mo/99Tc, 225Ra/225Ac and 186Re, was obtained as a function of target geometry, irradiation time and γ-beam energy. Optimized conditions for the generation of these radioisotopes of medical interest with the ELI-NP γ-beams were discussed. We estimated that a saturation specific activity of the order of 1-2 mCi/g can be achieved for thin targets with about one gram of mass considering a γ-beam flux of 10^{11} photons/s. Based on these results, we suggest that the ELI-NP facility can provide a unique possibility for the production of radioisotopes in sufficient quantities for nuclear medicine research.

  13. Kuiper Belt Object Orbiter Using Advanced Radioisotope Power Sources and Electric Propulsion

    NASA Technical Reports Server (NTRS)

    Oleson, Steven R.; McGuire, Melissa L.; Dankanich, John; Colozza, Anthony; Schmitz, Paul; Khan, Omair; Drexler, Jon; Fittje, James

    2011-01-01

    A joint NASA GRC/JPL design study was performed for the NASA Radioisotope Power Systems Office to explore the use of radioisotope electric propulsion for flagship class missions. The Kuiper Belt Object Orbiter is a flagship class mission concept projected for launch in the 2030 timeframe. Due to the large size of a flagship class science mission larger radioisotope power system building blocks were conceptualized to provide the roughly 4 kW of power needed by the NEXT ion propulsion system and the spacecraft. Using REP the spacecraft is able to rendezvous with and orbit a Kuiper Belt object in 16 years using either eleven (no spare) 420 W advanced RTGs or nine (with a spare) 550 W advanced Stirling Radioisotope systems. The design study evaluated integrating either system and estimated impacts on cost as well as required General Purpose Heat Source requirements.

  14. Potential medical applications of the plasma focus in the radioisotope production for PET imaging

    NASA Astrophysics Data System (ADS)

    Roshan, M. V.; Razaghi, S.; Asghari, F.; Rawat, R. S.; Springham, S. V.; Lee, P.; Lee, S.; Tan, T. L.

    2014-06-01

    Devices other than the accelerators are desired to be investigated for generating high energy particles to induce nuclear reaction and positron emission tomography (PET) producing radioisotopes. The experimental data of plasma focus devices (PF) are studied and the activity scaling law for External Solid Target (EST) activation is established. Based on the scaling law and the techniques to enhance the radioisotopes production, the feasibility of generating the required activity for PET imaging is studied.

  15. Personal reflections on the highlights and changes in radiation and radioisotope measurement applications

    NASA Astrophysics Data System (ADS)

    Gardner, Robin P.; Lee, Kyoung O.

    2015-11-01

    This paper describes the recent changes that the authors have perceived in the use of radiation and radioisotope measurement applications. The first change is that due to the increased use of Monte Carlo simulation which has occurred from a normal evolutionary process. This is due in large part to the increased accuracy that is being obtained by the use of detector response functions (DRFs) and the simultaneous increased computational efficiency that has become available with these DRFs, the availability of a greatly improved weight windows variance reduction method, and the availability of inexpensive computer clusters. This first change is a happy one. The other change that is occurring is in response to recent terrorist activities. That change is the replacement or major change in the use of long-lived radioisotopes in radioisotope measurement and other radioisotope source applications. In general this can be done by improving the security of these radioisotope sources or by replacing them altogether by using machine sources of radiation. In either case one would like to preclude altogether or at least minimize the possibility of terrorists being able to obtain radioisotopes and use them for clandestine purposes.

  16. Toward high performance radioisotope thermophotovoltaic systems using spectral control

    NASA Astrophysics Data System (ADS)

    Wang, Xiawa; Chan, Walker; Stelmakh, Veronika; Celanovic, Ivan; Fisher, Peter

    2016-12-01

    This work describes RTPV-PhC-1, an initial prototype for a radioisotope thermophotovoltaic (RTPV) system using a two-dimensional photonic crystal emitter and low bandgap thermophotovoltaic (TPV) cell to realize spectral control. We validated a system simulation using the measurements of RTPV-PhC-1 and its comparison setup RTPV-FlatTa-1 with the same configuration except a polished tantalum emitter. The emitter of RTPV-PhC-1 powered by an electric heater providing energy equivalent to one plutonia fuel pellet reached 950 °C with 52 W of thermal input power and produced 208 mW output power from 1 cm2 TPV cell. We compared the system performance using a photonic crystal emitter to a polished flat tantalum emitter and found that spectral control with the photonic crystal was four times more efficient. Based on the simulation, with more cell areas, better TPV cells, and improved insulation design, the system powered by a fuel pellet equivalent heat source is expected to reach an efficiency of 7.8%.

  17. Radioisotope Power Systems Reference Book for Mission Designers and Planners

    NASA Technical Reports Server (NTRS)

    Lee, Young; Bairstow, Brian

    2015-01-01

    The RPS Program's Program Planning and Assessment (PPA) Office commissioned the Mission Analysis team to develop the Radioisotope Power Systems (RPS) Reference Book for Mission Planners and Designers to define a baseline of RPS technology capabilities with specific emphasis on performance parameters and technology readiness. The main objective of this book is to provide RPS technology information that could be utilized by future mission concept studies and concurrent engineering practices. A progress summary from the major branches of RPS technology research provides mission analysis teams with a vital tool for assessing the RPS trade space, and provides concurrent engineering centers with a consistent set of guidelines for RPS performance characteristics. This book will be iterated when substantial new information becomes available to ensure continued relevance, serving as one of the cornerstone products of the RPS PPA Office. This book updates the original 2011 internal document, using data from the relevant publicly released RPS technology references and consultations with RPS technologists. Each performance parameter and RPS product subsection has been reviewed and cleared by at least one subject matter representative. A virtual workshop was held to reach consensus on the scope and contents of the book, and the definitions and assumptions that should be used. The subject matter experts then reviewed and updated the appropriate sections of the book. The RPS Mission Analysis Team then performed further updates and crosschecked the book for consistency. Finally, a second virtual workshop was held to ensure all subject matter experts and stakeholders concurred on the contents.

  18. Neptune Orbiters Utilizing Solar and Radioisotope Electric Propulsion

    NASA Technical Reports Server (NTRS)

    Fiehler, Douglas I.; Oleson, Steven R.

    2004-01-01

    In certain cases, Radioisotope Electric Propulsion (REP), used in conjunction with other propulsion systems, could be used to reduce the trip times for outer planetary orbiter spacecraft. It also has the potential to improve the maneuverability and power capabilities of the spacecraft when the target body is reached as compared with non-electric propulsion spacecraft. Current missions under study baseline aerocapture systems to capture into a science orbit after a Solar Electric Propulsion (SEP) stage is jettisoned. Other options under study would use all REP transfers with small payloads. Compared to the SEP stage/Aerocapture scenario, adding REP to the science spacecraft as well as a chemical capture system can replace the aerocapture system but with a trip time penalty. Eliminating both the SEP stage and the aerocapture system and utilizing a slightly larger launch vehicle, Star 48 upper stage, and a combined REP/Chemical capture system, the trip time can nearly be matched while providing over a kilowatt of science power reused from the REP maneuver. A Neptune Orbiter mission is examined utilizing single propulsion systems and combinations of SEP, REP, and chemical systems to compare concepts.

  19. Assessment of dynamic energy conversion systems for radioisotope heat sources

    SciTech Connect

    Thayer, G.R.; Mangeng, C.A.

    1985-06-01

    The use of dynamic conversion systems to convert the heat generated in a 7500 W(t) 90 Sr radioisotopic heat source to electricity is examined. The systems studies were Stirling; Brayton Cycle; three organic Rankines (ORCs) (Barber-Nichols/ORMAT, Sundstrand, and TRW); and an organic Rankine plus thermoelectrics. The systems were ranked for a North Warning System mission using a Los Alamos Multiattribute Decision Theory code. Three different heat source designs were used: case I with a beginning of life (BOL) source temperature of 640 C, case II with a BOL source temperature of 745/sup 0/C, and case III with a BOL source temperature of 945/sup 0/C. The Stirling engine system was the top-ranked system of cases I and II, closely followed by the ORC systems in case I and ORC plus thermoelectrics in case II. The Brayton cycle system was top-ranked for case III, with the Stirling engine system a close second. The use of /sup 238/Pu in heat source sizes of 7500 W(t) was examined and found to be questionable because of cost and material availability and because of additional requirements for analysis of safeguards and critical mass.

  20. Radioisotope tracer study in a sludge hygienization research irradiator (SHRI).

    PubMed

    Pant, H J; Thýn, J; Zitný, R; Bhatt, B C

    2001-01-01

    A radioisotope tracer study has been carried out in a batch type sludge hygienization research irradiator with flow from top to bottom, the objective being to measure flow rate, circulation and mixing times and to investigate the hydrodynamic behaviour of the irradiator for identifying the cause(s) of malfunction. A stimulus-response technique with NH4(82)Br as a tracer was used to measure the above parameters. Experiments were carried out at three different flow rates, i.e 1.0, 0.64 and 0.33 m3/min. Three combined models based on a set of differential equations are proposed and used to simulate the measured tracer concentration curves. The obtained parameters were used to estimate dead volume and analyse hydrodynamic behaviour of the irradiator. The nonlinear regression problem of model parameter estimation was solved using the Marquardt-Levenberg method. The measured flow rate was found to be in good agreement with the values shown by the flow meter. The circulation times were found to be half of the mixing times. A simple approach for estimation of dose based on a known vertical dose-rate profile inside the irradiator is presented. About one-fourth of the volume of the irradiator was found to be dead at lower flow rates and this decreased with increase in flow rate. At higher flow rates, a semi stagnant volume was found with slow exchange of flow between the active and dead volumes.

  1. Production of medical Sc radioisotopes with an alpha particle beam.

    PubMed

    Szkliniarz, Katarzyna; Sitarz, Mateusz; Walczak, Rafał; Jastrzębski, Jerzy; Bilewicz, Aleksander; Choiński, Jarosław; Jakubowski, Andrzej; Majkowska, Agnieszka; Stolarz, Anna; Trzcińska, Agnieszka; Zipper, Wiktor

    2016-12-01

    The internal α-particle beam of the Warsaw Heavy Ion Cyclotron was used to produce research quantities of the medically interesting Sc radioisotopes from natural Ca and K and isotopically enriched (42)Ca targets. The targets were made of metallic calcium, calcium carbonate and potassium chloride. New data on the production yields and impurities generated during the target irradiations are presented for the positron emitters (43)Sc, (44g)Sc and (44m)Sc. The different paths for the production of the long lived (44m)Sc/(44g)Sc in vivo generator, proposed by the ARRONAX team, using proton and deuteron beams as well as alpha-particle beams are discussed. Due to the larger angular momentum transfer in the formation of the compound nucleus in the case of the alpha particle induced reactions, the isomeric ratio of (44m)Sc/(44g)Sc at a bombarding energy of 29MeV is five times larger than previously determined for a deuteron beam and twenty times larger than for proton induced reactions on enriched CaCO3 targets. Therefore, formation of this generator via the alpha-particle route seems a very attractive way to form these isotopes. The experimental data presented here are compared with theoretical predictions made using the EMPIRE evaporation code. Reasonable agreement is generally observed.

  2. Target optimization for the photonuclear production of radioisotopes.

    PubMed

    Howard, Sean; Starovoitova, Valeriia N

    2015-02-01

    In this paper we discuss the optimum shape of a target for photonuclear production of radioisotopes using an electron linear accelerator. Different target geometries such as right cylinder, conical frustum, Gaussian volume of revolution and semi-ellipsoid have been considered for the production of (67)Cu via (68)Zn(γ,p)(67)Cu photonuclear reaction. The specific activity (SA) of (67)Cu was simulated for each target shape. Optimum ratio of radius to height for cylindrical targets was found to be between 0.2 and 0.25 for target masses ranging from 20 g to 100 g. It was shown that while some unconventional target shapes, such as semi-elliptical volume of revolution, result in slightly higher specific activities than cylindrical targets, the advantage is not significant and is outweighed by the complexity of the target production and handling. Power deposition into the target was modeled and the trade-off between the maximization of (67)Cu yield and the minimization of target heating has been discussed. The (67)Cu case can easily be extended for production of many other isotopes.

  3. Radioisotope-based Nuclear Power Strategy for Exploration Systems Development

    SciTech Connect

    Schmidt, George R.; Houts, Michael G.

    2006-01-20

    Nuclear power will play an important role in future exploration efforts. Its benefits pertain to practically all the different timeframes associated with the Exploration Vision, from robotic investigation of potential lunar landing sites to long-duration crewed missions on the lunar surface. However, the implementation of nuclear technology must follow a logical progression in capability that meets but does not overwhelm the power requirements for the missions in each exploration timeframe. It is likely that the surface power infrastructure, particularly for early missions, will be distributed in nature. Thus, nuclear sources will have to operate in concert with other types of power and energy storage systems, and must mesh well with the power architectures envisioned for each mission phase. Most importantly, they must demonstrate a clear advantage over other non-nuclear options (e.g., solar power, fuel cells) for their particular function. This paper describes a strategy that does this in the form of three sequential system developments. It begins with use of radioisotope generators currently under development, and applies the power conversion technology developed for these units to the design of a simple, robust reactor power system. The products from these development efforts would eventually serve as the foundation for application of nuclear power systems for exploration of Mars and beyond.

  4. Thermal vacuum life test facility for radioisotope thermoelectric generators

    NASA Astrophysics Data System (ADS)

    Deaton, R. L.; Goebel, C. J.; Amos, W. R.

    In the late 1970's, the Department of Energy (DOE) assigned Monsanto Research Corporation, Mound Facility, now operated by EG and G Mound Applied Technologies, the responsibility for assembling and testing General Purpose Heat Source (GPHS) radioisotope thermoelectric generators (RTGs). Assembled and tested were five RTGs, which included four flight units and one non-flight qualification unit. Figure 1 shows the RTG, which was designed by General Electric AstroSpace Division (GE/ASD) to produce 285 W of electrical power. A detailed description of the processes for RTG assembly and testing is presented by Amos and Goebel (1989). The RTG performance data are described by Bennett, et al., (1986). The flight units will provide electrical power for the National Aeronautics and Space Administration's (NASA) Galileo mission to Jupiter (two RTGs) and the joint NASA/European Space Agency (ESA) Ulysses mission to study the polar regions of the sun (one RTG). The remaining flight unit will serve as the spare for both missions, and a non-flight qualification unit was assembled and tested to ensure that performance criteria were adequately met.

  5. Analytical thermal model validation for Cassini radioisotope thermoelectric generator

    SciTech Connect

    Lin, E.I.

    1997-12-31

    The Saturn-bound Cassini spacecraft is designed to rely, without precedent, on the waste heat from its three radioisotope thermoelectric generators (RTGs) to warm the propulsion module subsystem, and the RTG end dome temperature is a key determining factor of the amount of waste heat delivered. A previously validated SINDA thermal model of the RTG was the sole guide to understanding its complex thermal behavior, but displayed large discrepancies against some initial thermal development test data. A careful revalidation effort led to significant modifications and adjustments of the model, which result in a doubling of the radiative heat transfer from the heat source support assemblies to the end domes and bring up the end dome and flange temperature predictions to within 2 C of the pertinent test data. The increased inboard end dome temperature has a considerable impact on thermal control of the spacecraft central body. The validation process offers an example of physically-driven analytical model calibration with test data from not only an electrical simulator but also a nuclear-fueled flight unit, and has established the end dome temperatures of a flight RTG where no in-flight or ground-test data existed before.

  6. Light-weight radioisotope heater unit (LWRHU) impact tests

    SciTech Connect

    Reimus, M.A.; Rinehart, G.H.; Herrera, A.; Lopez, B.; Lynch, C.; Moniz, P.

    1998-01-01

    The light-weight radioisotope heater unit (LWRHU) is a {sup 238}PuO{sub 2}-fueled heat source designed to provide one thermal watt in each of various locations on a spacecraft. Los Alamos National Laboratory designed, fabricated, and safety tested the LWRHU. The heat source consists of a hot-pressed {sup 238}PuO{sub 2} fuel pellet, a Pt-30Rh vented capsule, a pyrolytic graphite insulator, and a fineweave-pierced fabric graphite aeroshell assembly. To compare the performance of the LWRHUs fabricated for the Cassini mission with the performance of those fabricated for the Galileo mission, and to determine a failure threshold, two types of impact tests were conducted. A post-reentry impact test was performed on one of 180 flight-quality units produced for the Cassini mission and a series of sequential impact tests using simulant-fueled LWRHU capsules were conducted respectively. The results showed that deformation and fuel containment of the impacted Cassini LWRHU was similar to that of a previously tested Galileo LWRHU. Both units sustained minimal deformation of the aeroshell and fueled capsule; the fuel was entirely contained by the platinum capsule. Sequential impacting, in both end-on and side-on orientations, resulted in increased damage with each subsequent impact. Sequential impacting of the LWRHU appears to result in slightly greater damage than a single impact at the final impact velocity of 50 m/s. {copyright} {ital 1998 American Institute of Physics.}

  7. Light-weight radioisotope heater unit (LWRHU) impact tests

    SciTech Connect

    Reimus, M. A. H.; Rinehart, G. H.; Herrera, A.; Lopez, B.; Lynch, C.; Moniz, P.

    1998-01-15

    The light-weight radioisotope heater unit (LWRHU) is a {sup 238}PuO{sub 2}-fueled heat source designed to provide one thermal watt in each of various locations on a spacecraft. Los Alamos National Laboratory designed, fabricated, and safety tested the LWRHU. The heat source consists of a hot-pressed {sup 238}PuO{sub 2} fuel pellet, a Pt-30Rh vented capsule, a pyrolytic graphite insulator, and a fineweave-pierced fabric graphite aeroshell assembly. To compare the performance of the LWRHUs fabricated for the Cassini mission with the performance of those fabricated for the Galileo mission, and to determine a failure threshold, two types of impact tests were conducted. A post-reentry impact test was performed on one of 180 flight-quality units produced for the Cassini mission and a series of sequential impact tests using simulant-fueled LWRHU capsules were conducted respectively. The results showed that deformation and fuel containment of the impacted Cassini LWRHU was similar to that of a previously tested Galileo LWRHU. Both units sustained minimal deformation of the aeroshell and fueled capsule; the fuel was entirely contained by the platinum capsule. Sequential impacting, in both end-on and side-on orientations, resulted in increased damage with each subsequent impact. Sequential impacting of the LWRHU appears to result in slightly greater damage than a single impact at the final impact velocity of 50 m/s.

  8. Radioisotope Electric Propulsion Missions Utilizing a Common Spacecraft Design

    NASA Technical Reports Server (NTRS)

    Fiehler, Douglas; Oleson, Steven

    2004-01-01

    A study was conducted that shows how a single Radioisotope Electric Propulsion (REP) spacecraft design could be used for various missions throughout the solar system. This spacecraft design is based on a REP feasibility design from a study performed by NASA Glenn Research Center and the Johns Hopkins University Applied Physics Laboratory. The study also identifies technologies that need development to enable these missions. The mission baseline for the REP feasibility design study is a Trojan asteroid orbiter. This mission sends an REP spacecraft to Jupiter s leading Lagrange point where it would orbit and examine several Trojan asteroids. The spacecraft design from the REP feasibility study would also be applicable to missions to the Centaurs, and through some change of payload configuration, could accommodate a comet sample-return mission. Missions to small bodies throughout the outer solar system are also within reach of this spacecraft design. This set of missions, utilizing the common REP spacecraft design, is examined and required design modifications for specific missions are outlined.

  9. Variable Conductance Heat Pipes for Radioisotope Stirling Systems

    NASA Technical Reports Server (NTRS)

    Anderson, William G.; Tarau, Calin

    2008-01-01

    In a Stirling radioisotope system, heat must continually be removed from the GPHS modules, to maintain the GPHS modules and surrounding insulation at acceptable temperatures. Normally, the Stirling convertor provides this cooling. If the Stirling engine stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS, but also ending the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) was designed to allow multiple stops and restarts of the Stirling engine. A VCHP turns on with a delta T of 30 C, which is high enough to not risk standard ASRG operation but low enough to save most heater head life. This VCHP has a low mass, and low thermal losses for normal operation. In addition to the design, a proof-of-concept NaK VCHP was fabricated and tested. While NaK is normally not used in heat pipes, it has an advantage in that it is liquid at the reservoir operating temperature, while Na or K alone would freeze. The VCHP had two condensers, one simulating the heater head, and the other simulating the radiator. The experiments successfully demonstrated operation with the simulated heater head condenser off and on, while allowing the reservoir temperature to vary over 40 to 120 C, the maximum range expected. In agreement with previous NaK heat pipe tests, the evaporator delta T was roughly 70 C, due to distillation of the NaK in the evaporator.

  10. [L'application des radioisotopes a la chromatographie sur colonnes de celluloses substituees-IV L'analyse du mercure et du zinc dans le bismuth].

    PubMed

    Muzzarelli, R A; Marcotrigiano, G

    1967-03-01

    The Chromatographic behaviour of nanogram amounts of bismuth has been studied by radioisotope techniques on cellobiose, cellulose and seven substituted celluloses. All celluloses in ethyl ether adsorb bismuth, provided that it is as nitrate, and that excess of nitric acid is avoided. Bismuth can be eluted with thiocyanate in ether-methanol or with hydrochloric acid in methanol, depending on the retention strength of the various functional groups of celluloses. A very simple method of separation of bismuth from mercury over a wide range of concentration is presented.

  11. Separated Shoulder

    MedlinePlus

    Separated shoulder Overview By Mayo Clinic Staff A separated shoulder is an injury to the ligaments that hold your collarbone (clavicle) to your shoulder blade. In a mild separated shoulder, the ligaments ...

  12. Radioisotope Power System Delivery, Ground Support and Nuclear Safety Implementation: Use of the Multi-Mission Radioisotope Thermoelectric Generator for the NASA's Mars Science Laboratory

    SciTech Connect

    S.G. Johnson; K.L. Lively; C.C. Dwight

    2014-07-01

    Radioisotope power systems have been used for over 50 years to enable missions in remote or hostile environments. They are a convenient means of supplying a few milliwatts up to a few hundred watts of useable, long-term electrical power. With regard to use of a radioisotope power system, the transportation, ground support and implementation of nuclear safety protocols in the field is a complex process that requires clear identification of needed technical and regulatory requirements. The appropriate care must be taken to provide high quality treatment of the item to be moved so it arrives in a condition to fulfill its missions in space. Similarly it must be transported and managed in a manner compliant with requirements for shipment and handling of special nuclear material. This presentation describes transportation, ground support operations and implementation of nuclear safety and security protocols for a radioisotope power system using recent experience involving the Multi-Mission Radioisotope Thermoelectric Generator for National Aeronautics and Space Administration’s Mars Science Laboratory, which launched in November of 2011.

  13. Radioisotope electric propulsion of sciencecraft to the outer Solar System and near-interstellar space

    SciTech Connect

    Noble, R.J.

    1999-11-01

    Radioisotopes have been used successfully for more than 25 years to supply the heat for thermoelectric generators on various deep-space probes. Radioisotope electric propulsion (REP) systems have been proposed as low-thrust ion propulsion units based on radioisotope electric generators and ion thrusters. The perceived liability of radioisotope electric generators for ion propulsion is their high mass. Conventional radioisotope thermoelectric generators have a specific mass of about 200 kg/kW of electric power. Many development efforts have been undertaken with the aim of reducing the specific mass of radioisotope electric systems. Recent performance estimates suggest that specific masses of 50 kg/kW may be achievable with thermophotovoltaic and alkali metal thermal-to-electric conversion generators. Powerplants constructed from these near-term radioisotope electric generators and long-life ion thrusters will likely have specific masses in the range of 100 to 200 kg/kW of thrust power if development continues over the next decade. In earlier studies, it was concluded that flight times within the Solar System are indeed insensitive to reductions in the powerplant specific mass, and that a timely scientific program of robotic planetary rendezvous and near-interstellar space missions is enabled by primary electric propulsion once the powerplant specific mass is in the range of 100 to 200 kg/kW. Flight times can be substantially reduced by using hybrid propulsion schemes that combine chemical propulsion, gravity assist, and electric propulsion. Hybrid schemes are further explored in this article to illustrate how the performance of REP is enhanced for Pluto rendezvous, heliopause orbiter, and gravitational lens missions.

  14. An Overview and Status of NASA's Radioisotope Power Conversion Technology NRA

    NASA Technical Reports Server (NTRS)

    Anderson, David J.; Wong, Wayne A.; Tuttle, Karen L.

    2005-01-01

    NASA's Advanced Radioisotope Power Systems (RPS) development program is developing next generation radioisotope power conversion technologies that will enable future missions that have requirements that can not be met by either photovoltaic systems or by current Radioisotope Power System (RPS) technology. The Advanced Power Conversion Research and Technology project of the Advanced RPS development program is funding research and technology activities through the NASA Research Announcement (NRA) 02- OSS-01, "Research Opportunities in Space Science 2002" entitled "Radioisotope Power Conversion Technology" (RPCT), 13 August 2002. The objective of the RPCT NRA is to advance the development of radioisotope power conversion technologies to provide significant improvements over the state-of-practice General Purpose Heat Source/Radioisotope Thermoelectric Generator by providing significantly higher efficiency to reduce the number of radioisotope fuel modules, and increase specific power (watts/kilogram). Other Advanced RPS goals include safety, long-life, reliability, scalability, multi-mission capability, resistance to radiation, and minimal interference with the scientific payload. These advances would enable a factor of 2 to 4 decrease in the amount of fuel required to generate electrical power. The RPCT NRA selected advanced RPS power conversion technology research and development proposals in the following three areas: innovative RPS power conversion research, RPS power conversion technology development in a nominal 100We scale; and, milliwatt/multi-watt RPS (mWRPS) power conversion research. Ten RPCT NRA contracts were awarded in 2003 in the areas of Brayton, Stirling, thermoelectric (TE), and thermophotovoltaic (TPV) power conversion technologies. This paper will provide an overview of the RPCT NRA, and a brief summary of accomplishments over the first 18 months but focusing on advancements made over the last 6 months.

  15. Symptomatic rotator cuff tears show higher radioisotope uptake on bone scintigraphy compared with asymptomatic tears.

    PubMed

    Koike, Yoichi; Sano, Hirotaka; Kita, Atushi; Itoi, Eiji

    2013-09-01

    Some patients with rotator cuff tears complain of pain, whereas others are asymptomatic. Previous studies have pointed out the presence of active bone metabolism in the painful shoulder, identified with increased radioisotope uptake during bone scintigraphy. Shoulders with symptomatic rotator cuff tears will demonstrate higher radioisotope uptake than shoulders with asymptomatic tears with bone scintigraphy, reflecting active bone metabolism in symptomatic tears. Cross-sectional study; Level of evidence, 3. The study consisted of 3 groups: patients with symptomatic tears (symptomatic group), patients with asymptomatic tears (asymptomatic group), and controls (no tear group). The symptomatic group consisted of 28 shoulders from 28 patients with symptomatic rotator cuff tears (pain score ≤4 on the University of California, Los Angeles [UCLA] shoulder evaluation form) who underwent bone scintigraphy followed by rotator cuff repair. Of 70 volunteers who had previously undergone bone scintigraphy for diseases unrelated to their shoulder, 34 were selected for the asymptomatic group (pain score ≥8 on the UCLA shoulder form), and 32 were selected for the no tear group. The mean radioisotope uptake in the symptomatic group was significantly higher than that in the asymptomatic group (P = .02) and the no tear group (P = .02). Ten of 28 shoulders (36%) in the symptomatic group showed increased radioisotope uptake exceeding 2 standard deviations from the mean of the no tear group. This percentage was significantly higher when compared with the asymptomatic group (0%) (P < .01). Shoulders with a symptomatic rotator cuff tear showed higher radioisotope uptake on bone scintigraphy than those with an asymptomatic tear. The radioisotope uptake in shoulders with an asymptomatic tear was comparable with that in shoulders without a tear. Positive radioisotope uptake may be associated with pain in a subgroup of patients with rotator cuff tears.

  16. Small Radioisotope Power System at NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Dugala, Gina M.; Fraeman, Martin; Frankford, David P.; Duven, Dennis; Shamkovich, Andrei; Ambrose, Hollis; Meer, David W.

    2012-01-01

    In April 2009, NASA Glenn Research Center (GRC) formed an integrated product team (IPT) to develop a Small Radioisotope Power System (SRPS) utilizing a single Advanced Stirling Convertor (ASC) with passive balancer for possible use by the International Lunar Network (ILN) program. The ILN program is studying the feasibility of implementing a multiple node seismometer network to investigate the internal lunar structure. A single ASC produces approximately 80 W(sub e) and could potentially supply sufficient power for that application. The IPT consists of Sunpower, Inc., to provide the single ASC with balancer, The Johns Hopkins University Applied Physics Laboratory (JHU/APL) to design an engineering model Single Convertor Controller (SCC) for an ASC with balancer, and NASA GRC to provide technical support to these tasks and to develop a simulated lunar lander test stand. A controller maintains stable operation of an ASC. It regulates the alternating current produced by the linear alternator of the convertor, provides a specified output voltage, and maintains operation at a steady piston amplitude and hot end temperature. JHU/APL also designed an ASC dynamic engine/alternator simulator to aid in the testing and troubleshooting of the SCC. This paper describes the requirements, design, and development of the SCC, including some of the key challenges and the solutions chosen to overcome those issues. In addition, it describes the plans to analyze the effectiveness of a passive balancer to minimize vibration from the ASC, characterize the effect of ASC vibration on a lunar lander, characterize the performance of the SCC, and integrate the single ASC, SCC, and lunar lander test stand to characterize performance of the overall system.

  17. Small Radioisotope Power System Testing at NASA Glenn Research Center

    NASA Technical Reports Server (NTRS)

    Dugala, Gina; Bell, Mark; Oriti, Salvatore; Fraeman, Martin; Frankford, David; Duven, Dennis

    2013-01-01

    In April 2009, NASA Glenn Research Center (GRC) formed an integrated product team (IPT) to develop a Small Radioisotope Power System (SRPS) utilizing a single Advanced Stirling Convertor (ASC) with passive balancer. A single ASC produces approximately 80 We making this system advantageous for small distributed lunar science stations. The IPT consists of Sunpower, Inc., to provide the single ASC with a passive balancer, The Johns Hopkins University Applied Physics Laboratory (JHUAPL) to design an engineering model Single Convertor Controller (SCC) for an ASC with a passive balancer, and NASA GRC to provide technical support to these tasks and to develop a simulated lunar lander test stand. The single ASC with a passive balancer, simulated lunar lander test stand, and SCC were delivered to GRC and were tested as a system. The testing sequence at GRC included SCC fault tolerance, integration, electromagnetic interference (EMI), vibration, and extended operation testing. The SCC fault tolerance test characterized the SCCs ability to handle various fault conditions, including high or low bus power consumption, total open load or short circuit, and replacing a failed SCC card while the backup maintains control of the ASC. The integrated test characterized the behavior of the system across a range of operating conditions, including variations in cold-end temperature and piston amplitude, including the emitted vibration to both the sensors on the lunar lander and the lunar surface. The EMI test characterized the AC and DC magnetic and electric fields emitted by the SCC and single ASC. The vibration test confirms the SCCs ability to control the single ASC during launch. The extended operation test allows data to be collected over a period of thousands of hours to obtain long term performance data of the ASC with a passive balancer and the SCC. This paper will discuss the results of each of these tests.

  18. [Cancer therapy using unsealed radioisotopes-the present and future].

    PubMed

    Karasawa, Katsuyuki

    2014-12-01

    Iodine-131 (I-131) has been used for the ablation of residual thyroid remnants and cancer cells in well-differentiated thyroid cancers. It has also been used for metastatic well-differentiated thyroid cancers, especially lung and bone metastases. For small lung metastases, I-131 treatment has curative potential, particularly in young patients. Suppression of the thyroid stimulating hormone is also important for prolonging the survival of thyroid cancer patients. Strontium-89 (Sr-89) chloride has a mechanism similar to calcium, and it has been used for the treatment of bone metastases, especially osteoblastic metastases. It has been reported to have analgesic effects in an average of 76% of cases, and it is more effective if used in the early bone metastatic phase. Ibritumomab tiuxetan (Zevalin) is an anti-CD20 mouse monoclonal antibody labeled with Yttrium-90 (Y-90). It is used for treatment-resistant low grade or follicular B-cell non-Hodgkin's lymphomas and mantle lymphomas. Recently, radium-223 (Ra-223) has been used for bone metastases from castration resistant prostate cancers, and in a phase III trial, it has been proven to prolong survival of these patients. Cancer therapy using unsealed radioisotopes has been thought to be promising because it exhibits more targeted therapy than external beam irradiation. Therefore, if many more ideal targeting agents are developed in the future, this treatment might be used more commonly. As many agents such as I-131, Sr-89, and Ra-223 are available for treating bone metastasis, the combined use of other treatments such as high precision radiotherapy, bisphosphonates, hormonal agents, and molecular targeted agents should be investigated.

  19. Concept for a radioisotope powered dual mode lunar rover

    NASA Technical Reports Server (NTRS)

    Elliott, John O.; Schriener, Timothy M.; Coste, Keith

    2006-01-01

    Over three decades ago, the Apollo missions manifestly demonstrated the value of a lunar rover to expand the exploration activities of lunar astronauts. The stated plan of the new Vision for Space Exploration to establish a permanent presence on the moon in the next decades gives new impetus to providing long range roving and exploration capability in support of the siting, construction, and maintenance of future human bases. The incorporation of radioisotope power systems and telerobotic capability in the design has the potential to significantly expand the capability of such a rover, allowing continuous operation during the full lunar day/night cycle, as well as enabling exploration in permanently shadowed regions that may be of interest to humans for the resources they may hold. This paper describes a concept that builds on earlier studies originated in the Apollo program for a Dual Mode (crewed and telerobotic) Lunar Roving Vehicle (DMLRV). The goal of this vehicle would be to provide a multipurpose infrastructure element and remote science platform for the exploration of the moon. The DMLRV would be essential for extending the productivity of human exploration crews, and would provide a unique capability for diverse long-range, long-duration science exploration between human visits. With minimal reconfiguration this vehicle could also provide the basic platform to support a range of site survey and preparation activities in anticipation of the establishment of a permanent human presence on the moon. A conceptual design is presented for the DMLRV, including discussion of mission architecture, vehicle performance, representative science payload accommodation, and equipment and crew radiation considerations.

  20. Thermal Model Predictions of Advanced Stirling Radioisotope Generator Performance

    NASA Technical Reports Server (NTRS)

    Wang, Xiao-Yen J.; Fabanich, William Anthony; Schmitz, Paul C.

    2014-01-01

    This paper presents recent thermal model results of the Advanced Stirling Radioisotope Generator (ASRG). The three-dimensional (3D) ASRG thermal power model was built using the Thermal Desktop(trademark) thermal analyzer. The model was correlated with ASRG engineering unit test data and ASRG flight unit predictions from Lockheed Martin's (LM's) I-deas(trademark) TMG thermal model. The auxiliary cooling system (ACS) of the ASRG is also included in the ASRG thermal model. The ACS is designed to remove waste heat from the ASRG so that it can be used to heat spacecraft components. The performance of the ACS is reported under nominal conditions and during a Venus flyby scenario. The results for the nominal case are validated with data from Lockheed Martin. Transient thermal analysis results of ASRG for a Venus flyby with a representative trajectory are also presented. In addition, model results of an ASRG mounted on a Cassini-like spacecraft with a sunshade are presented to show a way to mitigate the high temperatures of a Venus flyby. It was predicted that the sunshade can lower the temperature of the ASRG alternator by 20 C for the representative Venus flyby trajectory. The 3D model also was modified to predict generator performance after a single Advanced Stirling Convertor failure. The geometry of the Microtherm HT insulation block on the outboard side was modified to match deformation and shrinkage observed during testing of a prototypic ASRG test fixture by LM. Test conditions and test data were used to correlate the model by adjusting the thermal conductivity of the deformed insulation to match the post-heat-dump steady state temperatures. Results for these conditions showed that the performance of the still-functioning inboard ACS was unaffected.

  1. Interplanetary Sample Return Missions Using Radioisotope Electric Propulsion

    NASA Technical Reports Server (NTRS)

    Williams, R.; Gao, Y.; Kluever, C. A.; Capples, M.; Belcher, J.

    2005-01-01

    Solar electric propulsion (SEP) is being used for a variety of planetary missions sponsored by ESA, JAXA, and NASA and nuclear electric propulsion (NEP) is being considered for future, flagship-class interplanetary missions. Radioisotope electric propulsion (REP) has recently been shown to effectively complement SEP and NEP for missions to high-AU targets with modest payload requirements. This paper investigates the application of an advanced REP for a sample return from the comet Tempel 1. A set of mission and system parameters are varied with the goal of quantifying their impact on total mission payload. Mission parameters considered include trip-time and Earth return entry interface speed of the sample return system. System parameters considered include launch vehicle, power level of spacecraft at beginning of mission, and thruster specific impulse. For the baseline case of Atlas 401 and REP power level of 750 W, the mission time was 12 years, the payload was 144 kg, and the missions optimized to a single specific impulse generally within Hall ion thruster range. Other cases were investigated in support of graduate studies, and include the larger Atlas 551 launch vehicle and extended power level to 1 kW. The Atlas 551 cases tended to optimize dual specific impulses generally in the Hall ion thruster range for both legs of the mission. A power level of at least 1-kW and trip-time of approximately 11 years was required to obtain a total science payload close to 320 kg for the Atlas 401 launch vehicle. An Atlas 551 launch vehicle yielded a science payload of approximately 540 kg for the case of 1-kW of power and an 11-year trip time, and nearly 250 kg of science payload for the case of 1-kW of power and a 6-year trip time. Results are also reported indicating the performance ramifications of meeting a reduced Earth entry interface velocity constraint.

  2. Concept for a radioisotope powered dual mode lunar rover

    NASA Technical Reports Server (NTRS)

    Elliott, John O.; Schriener, Timothy M.; Coste, Keith

    2006-01-01

    Over three decades ago, the Apollo missions manifestly demonstrated the value of a lunar rover to expand the exploration activities of lunar astronauts. The stated plan of the new Vision for Space Exploration to establish a permanent presence on the moon in the next decades gives new impetus to providing long range roving and exploration capability in support of the siting, construction, and maintenance of future human bases. The incorporation of radioisotope power systems and telerobotic capability in the design has the potential to significantly expand the capability of such a rover, allowing continuous operation during the full lunar day/night cycle, as well as enabling exploration in permanently shadowed regions that may be of interest to humans for the resources they may hold. This paper describes a concept that builds on earlier studies originated in the Apollo program for a Dual Mode (crewed and telerobotic) Lunar Roving Vehicle (DMLRV). The goal of this vehicle would be to provide a multipurpose infrastructure element and remote science platform for the exploration of the moon. The DMLRV would be essential for extending the productivity of human exploration crews, and would provide a unique capability for diverse long-range, long-duration science exploration between human visits. With minimal reconfiguration this vehicle could also provide the basic platform to support a range of site survey and preparation activities in anticipation of the establishment of a permanent human presence on the moon. A conceptual design is presented for the DMLRV, including discussion of mission architecture, vehicle performance, representative science payload accommodation, and equipment and crew radiation considerations.

  3. RADIOISOTOPE POWER SYSTEM CAPABILITIES AT THE IDAHO NATIONAL LABORATORY (INL)

    SciTech Connect

    Kelly Lively; Stephen Johnson; Eric Clarke

    2014-07-01

    --Idaho National Laboratory’s, Space Nuclear Systems and Technology Division established the resources, equipment and facilities required to provide nuclear-fueled, Radioisotope Power Systems (RPS) to Department of Energy (DOE) Customers. RPSs are designed to convert the heat generated by decay of iridium clad, 238PuO2 fuel pellets into electricity that is used to power missions in remote, harsh environments. Utilization of nuclear fuel requires adherence to governing regulations and the INL provides unique capabilities to safely fuel, test, store, transport and integrate RPSs to supply power—supporting mission needs. Nuclear capabilities encompass RPS fueling, testing, handling, storing, transporting RPS nationally, and space vehicle integration. Activities are performed at the INL and in remote locations such as John F. Kennedy Space Center and Cape Canaveral Air Station to support space missions. This paper will focus on the facility and equipment capabilities primarily offered at the INL, Material and Fuel Complex located in a security-protected, federally owned, industrial area on the remote desert site west of Idaho Falls, ID. Nuclear and non-nuclear facilities house equipment needed to perform required activities such as general purpose heat source (GPHS) module pre-assembly and module assembly using nuclear fuel; RPS receipt and baseline electrical testing, fueling, vibration testing to simulate the launch environment, mass properties testing to measure the mass and compute the moment of inertia, electro-magnetic characterizing to determine potential consequences to the operation of vehicle or scientific instrumentation, and thermal vacuum testing to verify RPS power performance in the vacuum and cold temperatures of space.

  4. Improving power density and efficiency of miniature radioisotopic thermoelectric generators

    NASA Astrophysics Data System (ADS)

    Whalen, Scott A.; Apblett, Christopher A.; Aselage, Terrence L.

    We have built and tested a prototype miniaturized thermoelectric power source that generates 450 μW of electrical power in a system volume of 4.3 cm 3. The measured power density of 104 μW cm -3 exceeds that of any previously reported thermoelectric power system of equivalent size. This improvement was achieved by implementing a novel thermopile design in which wagon wheel-shaped thermoelectric elements contact the entire circumference of the heat source whereas traditional approaches utilize only one heat source surface. The thermopile consists of 22 wagon wheel-shaped elements (11 P-N thermocouples) fabricated from 215-μm thick bismuth-telluride wafers having ZT = 0.97 at 30 °C. The power source operates on a 150 mW thermal input provided by an electrical resistance heater that simulates a capsule containing 0.4 g of 238PuO 2 located at the center of the device. Our primary research objective was to develop and demonstrate a prototype thermopile and radioisotopic thermoelectric generator (RTG) architecture with improved power density at small scales. Output power from this device, while optimized for efficiency, was not optimized for output voltage, and the maximum power was delivered at 41 mV. We also discuss modifications to our prototype design that result in significantly improved voltage and power. Numerical predictions show that a power output of 1.4 mW, power density of 329 μW cm -3, and voltage of 362 mV, is possible in the same package size.

  5. Radioisotope Productions for Medical Use with Accelerator Neutrons

    NASA Astrophysics Data System (ADS)

    Minato, Futoshi; Nagai, Yasuki; Iwamoto, Nobuyuki; Iwamoto, Osamu

    2014-09-01

    Various kinds of radioactive isotopes (RIs) are widely used in nuclear medicine for diagnostics and therapy. Since the RIs are not usually present in the nature, they must be produced by nuclear reactors and accelerators. For instance, 99mTc, which is the most common RI used in diagnosis, is mainly produc