EUTIMIO GUSTAVO FERNANDEZ NUNEZ
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Artigo IPEN-doc 23936 Radiotracers for different angiogenesis receptors in a melanoma model2012 - OLIVEIRA, ERICA A.; FAINTUCH, BLUMA L.; NUNEZ, EUTIMIO G.F.; MORO, ANA M.; NANDA, PRASANT K.; SMITH, CHARLES J.Early and reliable diagnosis of melanoma, a skin tumor with a poor prognosis, is extremely important. Phage display peptide libraries are a convenient screening resource for identifying bioactive peptides that interact with cancer targets. The aim of this study was to evaluate two technetium-99m tracers for angiogenesis detection in a melanoma model, using cyclic pegylated pentapeptide with RGD and NGR motifs conjugated with the bifunctional chelator mercaptoacetyltriglycine (MAG3). The conjugated peptides (10 ll of a lg/ll solution) were labeled with technetium-99m using a sodium tartrate buffer. Radiochemical evaluation was carried out by instant thin-layer chromatography and confirmed by high-performance liquid chromatography. The partition coefficient was determined and internalization assays were performed in two melanoma cell lines (B16F10 and SKMEL28). Biodistribution evaluation of the tracers was carried out in healthy animals at different time points and also in tumor-bearing mice, 120 min post injection. Blocking studies were also conducted by coinjection of cold peptides. The conjugates displayed a rather similar pharmacokinetic profile. They were radiolabeled with high radiochemical purity (> 97%) and both were hydrophilic with preferential renal excretion. Yet, tumor uptake was higher for human than for murine melanoma cells, especially for [99mTc]-MAG3-PEG8-c(RGDyk) (7.85± 2.34%injected dose/g 120 min post injection). The performance of [99mTc]-MAG3-PEG8-c(RGDyk) was better than the NGR tracer with regard to human melanoma uptake. In this sense, it should be considered for future radiotracer studies of tumor diagnosis. Melanoma Res 22:45–53 c 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.Artigo IPEN-doc 21229 Comparison of two peptide radiotracers for prostate carcinoma targeting2012 - FAINTUCH, BLUMA L.; OLIVEIRA, ERICA A.; NUNEZ, EUTIMIO G.F.; MORO, ANA M.; NANDA, P.K.; SMITH, CHARLES J.OBJECTIVES: Scintigraphy is generally not the first choice treatment for prostate cancer, although successful studies using bombesin analog radiopeptides have been performed. Recently, a novel peptide obtained using a phage display library demonstrated an affinity for prostate tumor cells. The aim of this study was to compare the use of a bombesin analog to that of a phage display library peptide (DUP-1) radiolabeled with technetium-99m for the treatment of prostate carcinoma. The peptides were first conjugated to S-acetyl-MAG3 with a 6-carbon spacer, namely aminohexanoic acid. METHODS: The technetium-99m labeling required a sodium tartrate buffer. Radiochemical evaluation was performed using ITLC and was confirmed by high-performance liquid chromatography. The coefficient partition was determined, and in vitro studies were performed using human prostate tumor cells. Biodistribution was evaluated in healthy animals at various time points and also in mice bearing tumors. RESULTS: The radiochemical purity of both radiotracers was greater than 95%. The DUP-1 tracer was more hydrophilic (log P = -2.41) than the bombesin tracer (log P = -0.39). The biodistribution evaluation confirmed this hydrophilicity by revealing the greater kidney uptake of DUP-1. The bombesin concentration in the pancreas was greater than that of DUP-1 due to specific gastrin-releasing peptide receptors. Bombesin internalization occurred for 78.32% of the total binding in tumor cells. The DUP-1 tracer showed very low binding to tumor cells during the in vitro evaluation, although tumor uptake for both tracers was similar. The tumors were primarily blocked by DUP- 1 and the bombesin radiotracer primarily targeted the pancreas. CONCLUSION: Further studies with the radiolabeled DUP-1 peptide are recommended. With further structural changes, this molecule could become an efficient alternative tracer for prostate tumor diagnosis.Artigo IPEN-doc 16980 Cintichem modified process sup(99)Mo precipitation step: application of statistical analysis tools over the reactional parameters2011 - TEODORO, RODRIGO; DIAS, CARLA R.B.R.; FERNANDEZ NUNEZ, EUTIMIO G.; OSSO JUNIOR, JOAO A.Tese IPEN-doc 16392 Desenvolvimento de conjugados de dextran manose radiomarcados para deteccao de linfonodo sentinela2011 - FERNANDEZ NUNEZ, EUTIMIO G.O diagnóstico precoce de tumores e metástase constitui atualmente o elemento de maior impacto dentro das políticas de saúde públicas contra o câncer. No câncer de mama e melanoma, a técnica de biópsia de linfonodo sentinela, para o diagnostico de metástase, tem sido muito utilizada evitando a dissecção total dos nodos da região anatômica afetada, e permitindo definir com precisão o procedimento terapêutico a utilizar. O objetivo principal deste trabalho centrou-se no desenvolvimento de conjugados radiomarcados de dextran-manose para diagnóstico, utilizando o núcleo de tecnécio altamente estável, [99mTc(CO)3]+. A cisteína, ligante tridentado, foi incorporada na estrutura dos conjugados, como agente quelante do Tecnécio-99m. As condições de marcação definidas para os produtos avaliados garantiram altos valores de pureza radioquímica (>90%) e atividade específica (>59,9 MBq/nmol) assim como uma alta estabilidade in vitro. Os conjugados de dextran-cisteína-manose demonstraram uma captação superior (4 vezes maior) nos nodos linfáticos em relação aos homólogos que não possuíam manose na estrutura. O conjugado de dextran-cisteína-manose de 30 kDa radiomarcado (99mTc-DCM2) foi o traçador com melhor desempenho biológico entre os avaliados à diferentes atividades injetadas. Demonstrou-se que concentrações superiores a 1 M favorecem a retenção do produto nos nodos linfáticos. As comparações com radiofármacos já utilizados no Brasil (Dextran-500 e Fitato) para detecção de linfonodo sentinela evidenciaram a superioridade do 99mTc-DCM2.Artigo IPEN-doc 18913 Radiotracers for different angiogenesis receptors in a melanoma model2012 - OLIVEIRA, ERICA A.; FAINTUCH, BLUMA L.; NUNEZ, EUTIMIO G.F.; MORO, ANA M.; NANDA, PRASANT K.; SMITH, CHARLES J.Artigo IPEN-doc 17842 Parameters optimization defined by statistical analysis for cysteine-dextran radiolabeling with technetium tricarbonyl core2011 - NUNEZ, EUTIMIO G.F.; FAINTUCH, BLUMA L.; TEODORO, RODRIGO; WIECEK, DANIELLE P.; SILVA, NATANAEL G.; PAPADOPOULOS, MINAS; PELECANOU, MARIA; PIRMETTIS, IOANNIS; OLIVEIRA FILHO, RENATO S. de; DUATTI, ADRIANO; PASQUALINI, ROBERTO; QUEIROZ, RODRIGO G.Artigo IPEN-doc 16453 Neovascularization after ischemic injury. Evaluation with sup(99m)Tc-HYNIC-RGD2011 - FAINTUCH, BLUMA L.; TEODORO, RODRIGO; OLIVEIRA, ERICA A. de; FERNANDEZ NUNEZ, EUTINMIO G.; FAINTUCH, JOELArtigo IPEN-doc 14527 Influence of colloid particle profile on sentinel lymph node uptake2009 - NUNEZ, EUTIMIO G.F.; FAINTUCH, BLUMA L.; TEODORO, RODRIGO; WIECEK, DANIELLE P.; MARTINELLI, JOSE R.; SILVA, NATANAEL G. da; CASTANHEIRA, CLAUDIA E.; OLIVEIRA FILHO, RENATO S. de; PASQUALINI, ROBERTOArtigo IPEN-doc 17833 Radiolabeled nano-peptides show specificity for an animal model of human PC3 prostate cancer cells2011 - FAINTUCH, BLUMA L.; FERNANDEZ NUNEZ, GUSTAVO E.; TEODORO, RODRIGO; MORO, ANA M.; MENGATTI, JAIRArtigo IPEN-doc 17841 Neurotensin(8-13) analogue: radiolabeling and biological evaluation using different chelators2011 - TEODORO, RODRIGO; FAINTUCH, BLUMA L.; NUNEZ, EUTIMIO G.F.; QUEIROZ, RODRIGO G.