Spelling suggestions: "subject:"indium111"" "subject:"indium""
1 |
Targeted Auger Electron Radiotherapy of HER2-amplified Breast CancerCostantini, Danny 23 September 2009 (has links)
Monoclonal antibodies (mAbs) conjugated to nuclear localization sequences (NLS) and labeled with Auger electron-emitters have great potential for targeted radiotherapy of cancer. This approach may be especially appropriate for the 25-30% of patients with breast cancer whose tumors display overexpression of HER2. Trastuzumab (Herceptin) is a humanized anti-HER2 mAb approved for immunotherapy of HER2-amplified breast cancer. The goal of this research was to radiolabel trastuzumab with [111]In, and to modify it with peptides harboring the NLS (CGYGPKKKRKVGG) of the simian virus 40 large-T antigen for targeted radiotherapy of breast cancer. It was hypothesized that the NLS-peptides would mediate the translocation of covalently linked [111]In-trastuzumab molecules into the nuclei of HER2-overexpressing breast cancer cells where subcellular-range Auger electrons are most damaging to DNA and lethal to cells.
Trastuzumab was derivatized with sulfosuccinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate for reaction with NLS-peptides and labeled with [111]In using diethylenetriaminepentaacetic acid. The dissociation constant for binding of [111]In-NLS-trastuzumab to HER2-overexpressing SK-BR-3 human breast cancer cells was reduced < 3-fold compared to [111]In-trastuzumab, demonstrating relatively preserved receptor-binding affinity. The NLS-peptides did not affect the biodistribution of [111]In-trastuzumab, but promoted its nuclear uptake in HER2-overexpressing MDA-MB-361 xenografts. The cytotoxicity of [111]In-NLS-trastuzumab on breast cancer cells correlated with their HER2 expression. Moreover, [111]In-NLS-trastuzumab was 2-fold and 5-fold more potent at killing MDA-MB-361 and SK-BR-3 cells compared to [111]In-trastuzumab, and nearly 3-fold and 6-fold more effective than unlabeled trastuzumab, respectively. Methotrexate is a known radiosensitizer that can amplify the lethal effects of ionizing radiation on tumor cells. Non-cytotoxic, but radiosensitizing doses of methotrexate were therefore combined with [111]In-NLS-trastuzumab; this enhanced the sensitivity of HER2-overexpressing breast cancer cells to [111]In-NLS-trastuzumab. The blood t1/2 of [111]In-NLS-trastuzumab in non-tumor bearing BALB/c mice was 23-34 h when administered intravenously or intraperitoneally. The maximum tolerated dose was 9.2-18.5 MBq; doses >18.5 MBq caused decreased leukocyte and platelet counts. [111]In-NLS-trastuzumab exhibited strong anti-tumor effects against HER2-overexpressing MDA-MB-361 xenografts, reducing their growth rate 2-fold and 3-fold compared to mice administered [111]In-trastuzumab or unlabeled trastuzumab, respectively.
These promising results suggest that [111]In-NLS-trastuzumab may be a useful Auger electron radioimmunotherapeutic agent for HER2-positive breast cancer in humans.
|
2 |
Targeted Auger Electron Radiotherapy of HER2-amplified Breast CancerCostantini, Danny 23 September 2009 (has links)
Monoclonal antibodies (mAbs) conjugated to nuclear localization sequences (NLS) and labeled with Auger electron-emitters have great potential for targeted radiotherapy of cancer. This approach may be especially appropriate for the 25-30% of patients with breast cancer whose tumors display overexpression of HER2. Trastuzumab (Herceptin) is a humanized anti-HER2 mAb approved for immunotherapy of HER2-amplified breast cancer. The goal of this research was to radiolabel trastuzumab with [111]In, and to modify it with peptides harboring the NLS (CGYGPKKKRKVGG) of the simian virus 40 large-T antigen for targeted radiotherapy of breast cancer. It was hypothesized that the NLS-peptides would mediate the translocation of covalently linked [111]In-trastuzumab molecules into the nuclei of HER2-overexpressing breast cancer cells where subcellular-range Auger electrons are most damaging to DNA and lethal to cells.
Trastuzumab was derivatized with sulfosuccinimidyl-4-(N-maleimidomethyl)-cyclohexane-1-carboxylate for reaction with NLS-peptides and labeled with [111]In using diethylenetriaminepentaacetic acid. The dissociation constant for binding of [111]In-NLS-trastuzumab to HER2-overexpressing SK-BR-3 human breast cancer cells was reduced < 3-fold compared to [111]In-trastuzumab, demonstrating relatively preserved receptor-binding affinity. The NLS-peptides did not affect the biodistribution of [111]In-trastuzumab, but promoted its nuclear uptake in HER2-overexpressing MDA-MB-361 xenografts. The cytotoxicity of [111]In-NLS-trastuzumab on breast cancer cells correlated with their HER2 expression. Moreover, [111]In-NLS-trastuzumab was 2-fold and 5-fold more potent at killing MDA-MB-361 and SK-BR-3 cells compared to [111]In-trastuzumab, and nearly 3-fold and 6-fold more effective than unlabeled trastuzumab, respectively. Methotrexate is a known radiosensitizer that can amplify the lethal effects of ionizing radiation on tumor cells. Non-cytotoxic, but radiosensitizing doses of methotrexate were therefore combined with [111]In-NLS-trastuzumab; this enhanced the sensitivity of HER2-overexpressing breast cancer cells to [111]In-NLS-trastuzumab. The blood t1/2 of [111]In-NLS-trastuzumab in non-tumor bearing BALB/c mice was 23-34 h when administered intravenously or intraperitoneally. The maximum tolerated dose was 9.2-18.5 MBq; doses >18.5 MBq caused decreased leukocyte and platelet counts. [111]In-NLS-trastuzumab exhibited strong anti-tumor effects against HER2-overexpressing MDA-MB-361 xenografts, reducing their growth rate 2-fold and 3-fold compared to mice administered [111]In-trastuzumab or unlabeled trastuzumab, respectively.
These promising results suggest that [111]In-NLS-trastuzumab may be a useful Auger electron radioimmunotherapeutic agent for HER2-positive breast cancer in humans.
|
3 |
Optimum ¹¹¹In okine labelled autologous leukocytesDeTurk, Kenneth Wayne 01 January 1989 (has links)
The purpose of this study is to determine the optimum conditions for obtaining a leukocyte button which most effectively will be subsequently labelled with 111In oxine. As in all radiopharmaceuticals, the highest radiopharmaceutical purity, or the fraction of total radioactivity in the desired radiopharmaceutical form (111In oxine leukocyte), the better the product. Many 111In ocine labelled leukocytes are contaminated by labelled platelets, red cells, and proteins, resulting in a “dirty” product. But with careful leukocyte culturing, sedimentation, centrifugation, and labelling, as demonstrated by this study, a highly desirable, pure radiopharmaceutical can be made. In an attempt to further purify the leukocyte button beyond centrifugation, hypotonic red cell lysing and its effect on leukocyte viability will be studied. The optimum incubation time will be determined by examining the leukocyte and red cell elution profiles at different incubation times. And, 0.9% saline washes of plasma and proteins from the leukocytes will be varied by both volume and number to determine if extra washes will optimize the labelling efficiency.
|
4 |
89Zr-Imuno-PET/111In-Imuno- SPECT: desenvolvimento radiofarmacêutico de agentes de imagem molecular para receptores EGF / 89Zr immuno-PET/111In imuno-SPECT: Radiopharmaceutical development of molecular imaging agents for EGF receptorsRaquel Benedetto 08 December 2017 (has links)
A baixa seletividade dos métodos convencionais para diagnóstico e terapia de neoplasias, bem como o fato de nem sempre alcançarem o sucesso terapêutico desejado, configuram dificuldades para a prática oncológica. Diante disso, os anticorpos monoclonais (AcMs) radiomarcados, aplicados em técnicas diagnósticas, têm se destacado, visto que permitem a entrega seletiva da radiação ao alvo de interesse. A metodologia Radioimunodiagnóstico (RID), utilizando AcM anti-EGFR radiomarcado, possibilita triagem prévia, avaliando a resistência ao tratamento e estratificando pacientes que possam apresentar benefícios à imunoterapia com cetuximabe. Além disso, permite monitorar a progressão da terapia, visando tratamento mais efetivo e direcionado, promulgando a abordagem da medicina personalizada. No Brasil, ainda não há radioimunoconjugado disponível para diagnóstico e seguimento do câncer. Nesse contexto, o objetivo com este trabalho foi o de desenvolver uma formulação farmacêutica para padronizar uma rotina de produção dos radiofármacos para radioimunodiagnóstico de câncer de cabeça e pescoço e de câncer colorretal: cetuximabe-DTPA-111In e cetuximabe-DFO-89Zr. Em adição, corroborar na elucidação dos mecanismos de resistência das células tumorais à terapia com o cetuximabe, através da realização de estudos de ligação do radioimunoconjugado à receptores celulares. Em relação aos radiofármacos estudados, destaca-se que os processos de conjugação do cetuximabe com os quelantes DTPA, na razão molar 1:20, e com o DFO, 1:5, foram bem-sucedidos e otimizados, demonstrando boa reprodutibilidade. Os imunoconjugados apresentaram preservação da imunorreatividade e alta estabilidade quando armazenados a -20°C por até seis meses. Esses imunoconjugados, quando radiomarcado com 111In e 89Zr, exibiram pureza radioquímica superior a 95%, sem necessidade de purificação pós-marcação, e estabilidade por tempo que possibilita seu transporte às clínicas distantes do centro produtor. As análises in vitro do cetuximabe-DTPA-111In em células FaDu-C10 (linhagem resistente) demonstraram percentual inexpressivo de ligação e internalização do radioimunoconjugado, congruindo na explanação do modelo de resistência conferido à linhagem. O estudo de corpo inteiro em MicroPET/TC revelou redução no perfil de captação no grupo de bloqueio, com excesso de cetuximabe não marcado, e intensa captação do cetuximabe-DFO-89Zr pelo tumor de células escamosas no grupo sem bloqueador, confirmando a especificidade in vivo do radioimunoconjugado. Os estudos de biodistribuição dos radiofármacos foram compatíveis com os descritos em literatura e validaram os resultados obtidos por imagens em MicroSPECT/TC e MicroPET/TC, além de apresentarem apreciável captação tumoral, considerando os tempos analisados. A estabilidade alta in vivo e a eficácia da marcação foram confirmadas pela baixa captação óssea e em tecidos não alvos. O melhor intervalo pós-injeção do radiofármaco para avaliação in vivo foi após cinco dias da administração. Conclui-se, portanto, que os radioimunoconjugados para imuno-SPECT e imuno-PET, cetuximabe-DTPA-111In e cetuximabe-DFO-89Zr, são ferramentas promissoras para diagnóstico e monitoramento de câncer receptor específico (EGFR) e para estratificação de pacientes à terapia anti-EGFR, encorajando a continuidade deste projeto para futuros estudos clínicos. / The low selectivity of conventional methods for cancer diagnosis and therapy, as well as the fact that these methods could not achieve the desired therapeutic success, constitute difficulties for the oncological practice. In this regard, radiolabeled monoclonal antibodies (mAbs) applied in diagnostic techniques have been highlighted, since they allow the selective delivery of the radiation to the specific target. The radioimmunodiagnosis methodology (RID), using radiolabeled anti-EGFR mAbs, enables previous screening, evaluating resistance to treatment and stratifying patients who may present benefits to cetuximab immunotherapy. In addition, it allows monitoring the progression of the therapy, aiming for a more effective and directed treatment, leading the personalized medicine approach. A radioimmunoconjugate is not yet available for diagnosis and management of cancer in Brazil. In this context, this research was carried out to develop a pharmaceutical formulation to standardize a routine production of radiopharmaceuticals for diagnosis and monitoring head and neck cancer and colorectal carcinoma: 111In-DTPA-cetuximab and 89Zr-DFO-cetuximab. In addition, corroborate in the elucidation of the tumor cells resistance mechanisms to EGFR-targeted therapy, through in vitro and in vivo radioimmunoconjugate binding studies to cellular receptors. Regarding to the radiopharmaceuticals studied, cetuximab was conjugated to DTPA chelator at 1:20 molar ratio and to DFO at 1: 5, and these processes were successful and optimized, showing good reproducibility. Immunoconjugates showed preservation of immunoreactivity and high stability when stored at -20 °C for up to 6 months. These immunoconjugates when radiolabeled with 111In and 89Zr have exhibited radiochemical purity above 95%, without any post-labeling purification, and the radioimmunoconjugates have demonstrated stability for a time that allows them to be transported to clinics far from the producer center. 111In-DTPA-cetuximab in vitro analyzes in FaDu-C10 cells (resistant cell line) has presented an inexpressive percentage of binding and internalization of the radioimmunoconjugate, ensuring the resistance model conferred to this cell line. The MicroPET/CT imaging study has revealed a reduction in uptake profile for \"Blocking\" group, with an excess of unlabeling cetuximab, and an intense 89Zr-DFO-cetuximab uptake in squamous cell tumor for \"Non-blocking\" group, that evidenced the in vivo radioimmunoconjugate specificity. The biodistribution studies of the radiopharmaceuticals were well-matched with those described in the literature and they validated the results obtained through the MicroSPECT/CT and MicroPET/ CT images. In addition, these studies in vivo have displayed a substantial tumor uptake, according with the analyzed time points. The radioimmunoconjugate showed high in vivo stability and labeling procedures efficiency, which were confirmed by low bone and non-target tissues uptake. The best post-injection interval for in vivo evaluation is after 5 days of radioimmunoconjugate administration. In conclusion, the radioimmunoconjugates for immuno-SPECT and immuno-PET, 111In-DTPA-cetuximab and 89Zr-DFO-cetuximab, are promising tools for diagnosis and monitoring of specific receptor cancer (EGFR), as well as for stratification of patients to anti-EGFR therapy, and thus encourages the continuity of this project for future clinical trials.
|
5 |
89Zr-Imuno-PET/111In-Imuno- SPECT: desenvolvimento radiofarmacêutico de agentes de imagem molecular para receptores EGF / 89Zr immuno-PET/111In imuno-SPECT: Radiopharmaceutical development of molecular imaging agents for EGF receptorsBenedetto, Raquel 08 December 2017 (has links)
A baixa seletividade dos métodos convencionais para diagnóstico e terapia de neoplasias, bem como o fato de nem sempre alcançarem o sucesso terapêutico desejado, configuram dificuldades para a prática oncológica. Diante disso, os anticorpos monoclonais (AcMs) radiomarcados, aplicados em técnicas diagnósticas, têm se destacado, visto que permitem a entrega seletiva da radiação ao alvo de interesse. A metodologia Radioimunodiagnóstico (RID), utilizando AcM anti-EGFR radiomarcado, possibilita triagem prévia, avaliando a resistência ao tratamento e estratificando pacientes que possam apresentar benefícios à imunoterapia com cetuximabe. Além disso, permite monitorar a progressão da terapia, visando tratamento mais efetivo e direcionado, promulgando a abordagem da medicina personalizada. No Brasil, ainda não há radioimunoconjugado disponível para diagnóstico e seguimento do câncer. Nesse contexto, o objetivo com este trabalho foi o de desenvolver uma formulação farmacêutica para padronizar uma rotina de produção dos radiofármacos para radioimunodiagnóstico de câncer de cabeça e pescoço e de câncer colorretal: cetuximabe-DTPA-111In e cetuximabe-DFO-89Zr. Em adição, corroborar na elucidação dos mecanismos de resistência das células tumorais à terapia com o cetuximabe, através da realização de estudos de ligação do radioimunoconjugado à receptores celulares. Em relação aos radiofármacos estudados, destaca-se que os processos de conjugação do cetuximabe com os quelantes DTPA, na razão molar 1:20, e com o DFO, 1:5, foram bem-sucedidos e otimizados, demonstrando boa reprodutibilidade. Os imunoconjugados apresentaram preservação da imunorreatividade e alta estabilidade quando armazenados a -20°C por até seis meses. Esses imunoconjugados, quando radiomarcado com 111In e 89Zr, exibiram pureza radioquímica superior a 95%, sem necessidade de purificação pós-marcação, e estabilidade por tempo que possibilita seu transporte às clínicas distantes do centro produtor. As análises in vitro do cetuximabe-DTPA-111In em células FaDu-C10 (linhagem resistente) demonstraram percentual inexpressivo de ligação e internalização do radioimunoconjugado, congruindo na explanação do modelo de resistência conferido à linhagem. O estudo de corpo inteiro em MicroPET/TC revelou redução no perfil de captação no grupo de bloqueio, com excesso de cetuximabe não marcado, e intensa captação do cetuximabe-DFO-89Zr pelo tumor de células escamosas no grupo sem bloqueador, confirmando a especificidade in vivo do radioimunoconjugado. Os estudos de biodistribuição dos radiofármacos foram compatíveis com os descritos em literatura e validaram os resultados obtidos por imagens em MicroSPECT/TC e MicroPET/TC, além de apresentarem apreciável captação tumoral, considerando os tempos analisados. A estabilidade alta in vivo e a eficácia da marcação foram confirmadas pela baixa captação óssea e em tecidos não alvos. O melhor intervalo pós-injeção do radiofármaco para avaliação in vivo foi após cinco dias da administração. Conclui-se, portanto, que os radioimunoconjugados para imuno-SPECT e imuno-PET, cetuximabe-DTPA-111In e cetuximabe-DFO-89Zr, são ferramentas promissoras para diagnóstico e monitoramento de câncer receptor específico (EGFR) e para estratificação de pacientes à terapia anti-EGFR, encorajando a continuidade deste projeto para futuros estudos clínicos. / The low selectivity of conventional methods for cancer diagnosis and therapy, as well as the fact that these methods could not achieve the desired therapeutic success, constitute difficulties for the oncological practice. In this regard, radiolabeled monoclonal antibodies (mAbs) applied in diagnostic techniques have been highlighted, since they allow the selective delivery of the radiation to the specific target. The radioimmunodiagnosis methodology (RID), using radiolabeled anti-EGFR mAbs, enables previous screening, evaluating resistance to treatment and stratifying patients who may present benefits to cetuximab immunotherapy. In addition, it allows monitoring the progression of the therapy, aiming for a more effective and directed treatment, leading the personalized medicine approach. A radioimmunoconjugate is not yet available for diagnosis and management of cancer in Brazil. In this context, this research was carried out to develop a pharmaceutical formulation to standardize a routine production of radiopharmaceuticals for diagnosis and monitoring head and neck cancer and colorectal carcinoma: 111In-DTPA-cetuximab and 89Zr-DFO-cetuximab. In addition, corroborate in the elucidation of the tumor cells resistance mechanisms to EGFR-targeted therapy, through in vitro and in vivo radioimmunoconjugate binding studies to cellular receptors. Regarding to the radiopharmaceuticals studied, cetuximab was conjugated to DTPA chelator at 1:20 molar ratio and to DFO at 1: 5, and these processes were successful and optimized, showing good reproducibility. Immunoconjugates showed preservation of immunoreactivity and high stability when stored at -20 °C for up to 6 months. These immunoconjugates when radiolabeled with 111In and 89Zr have exhibited radiochemical purity above 95%, without any post-labeling purification, and the radioimmunoconjugates have demonstrated stability for a time that allows them to be transported to clinics far from the producer center. 111In-DTPA-cetuximab in vitro analyzes in FaDu-C10 cells (resistant cell line) has presented an inexpressive percentage of binding and internalization of the radioimmunoconjugate, ensuring the resistance model conferred to this cell line. The MicroPET/CT imaging study has revealed a reduction in uptake profile for \"Blocking\" group, with an excess of unlabeling cetuximab, and an intense 89Zr-DFO-cetuximab uptake in squamous cell tumor for \"Non-blocking\" group, that evidenced the in vivo radioimmunoconjugate specificity. The biodistribution studies of the radiopharmaceuticals were well-matched with those described in the literature and they validated the results obtained through the MicroSPECT/CT and MicroPET/ CT images. In addition, these studies in vivo have displayed a substantial tumor uptake, according with the analyzed time points. The radioimmunoconjugate showed high in vivo stability and labeling procedures efficiency, which were confirmed by low bone and non-target tissues uptake. The best post-injection interval for in vivo evaluation is after 5 days of radioimmunoconjugate administration. In conclusion, the radioimmunoconjugates for immuno-SPECT and immuno-PET, 111In-DTPA-cetuximab and 89Zr-DFO-cetuximab, are promising tools for diagnosis and monitoring of specific receptor cancer (EGFR), as well as for stratification of patients to anti-EGFR therapy, and thus encourages the continuity of this project for future clinical trials.
|
6 |
111In-labeled Nimotuzumab Modified with Nuclear Localization Sequences (NLS): An Auger Electron-emitting Radiotherapeutic Agent for EGFR-overexpressing and Trastuzumab-resistant Breast CancerFasih, Aisha 24 August 2011 (has links)
Objective: The cytotoxic property of anti-EGFR-1 monoclonal-antibody nimotuzumab modified with nuclear localization sequence and radiolabeled with 111In was evaluated in trastuzumab-resistant breast cancer cells. Methods: 111In-nimotuzumab-NLS was constructed and its immunoreactivity was determined. Cellular and nuclear uptake was evaluated by cell fractionation. Finally, the cytotoxicity of conjugates (111In-nimotuzumab/111In-nimotuzumab-NLS) was studied by clonogenic assays. Results: The immunoreactivity of 111In-nimotuzumab-NLS was conserved. 111In-nimotuzumab-NLS exhibited 2-fold higher nuclear translocation as compared to 111In-nimotuzumab in MDA-MB-468 cells. Nuclear importation of 111In-nimotuzumab-NLS in MDA-MB-468 cells was 4-fold and 6-fold higher than moderate and low EGFR expressing cell lines, respectively. Clonogenic survival (CS) for MDA-MB-468 cells showed 111In-nimotuzumab-NLS to be 10-folds and 60-folds more potent than 111In-nimotuzumab and nimotuzumab, respectively. Moderate killing for TrR1 and MDA-MB-231 was observed. 111In-hEGF showed significantly higher cytotoxicity and 2-fold higher γ-H2AX foci integrated density/nuclear-area as compared to 111In-nimotuzumab-NLS. Preserved selectivity of 111In-nimotuzumab-NLS makes it an excellent drug for treating cancers.
|
7 |
111In-labeled Nimotuzumab Modified with Nuclear Localization Sequences (NLS): An Auger Electron-emitting Radiotherapeutic Agent for EGFR-overexpressing and Trastuzumab-resistant Breast CancerFasih, Aisha 24 August 2011 (has links)
Objective: The cytotoxic property of anti-EGFR-1 monoclonal-antibody nimotuzumab modified with nuclear localization sequence and radiolabeled with 111In was evaluated in trastuzumab-resistant breast cancer cells. Methods: 111In-nimotuzumab-NLS was constructed and its immunoreactivity was determined. Cellular and nuclear uptake was evaluated by cell fractionation. Finally, the cytotoxicity of conjugates (111In-nimotuzumab/111In-nimotuzumab-NLS) was studied by clonogenic assays. Results: The immunoreactivity of 111In-nimotuzumab-NLS was conserved. 111In-nimotuzumab-NLS exhibited 2-fold higher nuclear translocation as compared to 111In-nimotuzumab in MDA-MB-468 cells. Nuclear importation of 111In-nimotuzumab-NLS in MDA-MB-468 cells was 4-fold and 6-fold higher than moderate and low EGFR expressing cell lines, respectively. Clonogenic survival (CS) for MDA-MB-468 cells showed 111In-nimotuzumab-NLS to be 10-folds and 60-folds more potent than 111In-nimotuzumab and nimotuzumab, respectively. Moderate killing for TrR1 and MDA-MB-231 was observed. 111In-hEGF showed significantly higher cytotoxicity and 2-fold higher γ-H2AX foci integrated density/nuclear-area as compared to 111In-nimotuzumab-NLS. Preserved selectivity of 111In-nimotuzumab-NLS makes it an excellent drug for treating cancers.
|
8 |
Desenvolvimento de novo metodo de producao de sup(111)In a partir da irradiacao de Cd com protonsLION, LUCIANA F. de 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:46:45Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:46Z (GMT). No. of bitstreams: 1
08358.pdf: 3987174 bytes, checksum: bd5e0ea6705a189997deab3c68d85291 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP / FAPESP:99/08249-9
|
9 |
Desenvolvimento de reagente liofilizado de glucoheptonato - estanho para marcação de leucócitos com tecnécio-99m in vitroNASCIMENTO, ROSEMEIRE F. 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:55:02Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:05:57Z (GMT). No. of bitstreams: 0 / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP
|
10 |
Desenvolvimento de novo metodo de producao de sup(111)In a partir da irradiacao de Cd com protonsLION, LUCIANA F. de 09 October 2014 (has links)
Made available in DSpace on 2014-10-09T12:46:45Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T13:56:46Z (GMT). No. of bitstreams: 1
08358.pdf: 3987174 bytes, checksum: bd5e0ea6705a189997deab3c68d85291 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Dissertacao (Mestrado) / IPEN/D / Instituto de Pesquisas Energeticas e Nucleares - IPEN/CNEN-SP / FAPESP:99/08249-9
|
Page generated in 0.0241 seconds