LUIS ALBERTO PEREIRA DIAS
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Artigo IPEN-doc 28654 In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-1772022 - BOAS, CRISTIAN A.W.V.; SILVA, JEFFERSON de J.; DIAS, LUIS A.P.; FREIRE, MARIA R.B.; BALIEIRO, LUIZA M.; SANTOS, CAROLINA S.F. dos; VIVALDINI, BIANCA F.; BENEDETTO, RAQUEL; VIEIRA, DANIEL P.; PASSOS, PRISCILA de Q.S.; MARUMO, MARIA H.; TEIXEIRA, LUIS F.S.; ARAUJO, ELAINE B. deThe PSMA-targeted radionuclide therapy has been explored since 2015 with radioisotope lutetium-177, whose β− emission range is adequate for micrometastases treatment. This radioisotope is obtained by two different production routes that directly affect the specific activity of lutetium-177 (non-carrier added and carrier added) and, consequently, the specific activity of radiopharmaceuticals, like 177Lu-PSMA-617. The influence of the specific activity of lutetium-177 on the properties of the radiopharmaceutical PSMA-617 was evaluated through pre-clinical studies. The in vitro study pointed to a lower constant of dissociation with non-carrier added lutetium-177 due to the difference in the specific activity. However, competition and internalization assays resulted in similar results for both lutetium-177. Based on these pre-clinical experiments, the total in vitro tumor cell binding and tumor uptake in vivo were similar, with no influence of the specific activity of the 177Lu-PSMA-617. Regardless the specific activity did not directly affect tumor uptake, the tumor/non-target organs ratios were higher for the radiopharmaceutical labeled with carrier added lutetium-177, which had the lowest specific activity.Artigo IPEN-doc 22622 In vitro cytotoxic and genotoxic evaluation of peptides used in nuclear medicine (DOTATATE and Ubiquicidin29-41) in CHO-K1 cells2016 - OCAMPO, IVETTE Z.; PASSOS, PRISCILA de Q.S.; CARVALHO, LUMA R. de; CRUZ, CAMILA A.L. da; ESTEVES-PEDRO, NATALIA M.; SILVA, FABIANA M. da; HIGA, OLGA Z.; DIAS, LUIZ A.P.; OKAZAKI, KAYO; VIEIRA, DANIEL P.Micronucleus (MN) assay constitutes a valuable surrogate to the chromosome aberration technique for in vitro testing of the genotoxicity of substances. As test substances, two peptidic compounds (DOTATATE and Ubiquicidin29-41) used in nuclear medicine, were tested for in vitro cytotoxicity and genotoxicity in CHO-K1 cells. None of the compounds showed detectable cytotoxicity (0.5– 7.3 ng/mL for DOTATATE and 0.3–4.5 ng/mL for UBI29-41), genotoxicity (0.72, 7.2 and 72.0 ng/ml for DOTATATE and 0.45, 4.5 and 45.0 ng/mL for UBI29-41) or cell cycle changes as compared to untreated controls at the concentrations tested. Statistical analysis showed good concordance between two independent analysts. The results corroborate the notion of the safety of the compounds and present improvements of the in vitro MN assay when performed in a pre-clinical trial context that increase the throughput of small-to-medium testing facilities as an alternative to high content screening systems.