JEFFERSON DE JESUS SILVA
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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.Resumo IPEN-doc 26856 177Lu-PSMA-6172019 - BOAS, CRISTIAN W.V.; SILVA, JEFFERSON de J.; BENEDETTO, RAQUEL; MENGATTI, JAIR; ARAUJO, ELAINE B. deIntroduction: PSMA-617 radiolabeled with lutetium-177 has shown good results in compassionate studies around the world, and there is great interest in this kind of therapy in Brazil. The Nuclear and Research Institute (IPEN-CNEN) in São Paulo city, is a national radiopharmaceutical producer and the distribution of radiopharmaceuticals for therapy in a country of continental dimensions such as Brazil, becomes a challenge from the standpoint of guaranteeing the stability of the product. This work evaluated the scheduling of pilot batches for the production of 177Lu-PSMA-617 and studied the effect of dilution and freezing on the stability of mono-doses of the product. Materials and Methods: Radiolabeling of PSMA-617 (ABX, Germany) with lutetium-177 (JSC, Russia) was performed in heating block at 90 °C for 30 minutes, 37 GBq (1 Ci), 500 μg of peptide and sodium ascorbate (0,5 M pH 4,7) as buffer. At the end of the radiolabel, 0,5 mL of DTPA solution (4 mg/mL pH 4,5) was added and the product was diluted with an appropriate volume of saline solution 0,9%. The final product was filtrated in 0.22 membrane and the doses were fractionated (7,4 GBq calibrated for 24 hours in approximately 2,4 mL) and conditioned in appropriate lead chambers inside a dry ice bucket for transport simulation. The radiochemical purity (RP) was evaluated in a stability study at, 24 and 48 hours by TLC and HPLC. The radionuclidic purity, sterility and bacterial endotoxins were also evaluated. Results and discussion: The radiopharmaceutical was stable after 48 hours (99.47% TLC and 99.39% HPLC), and was approved in radionuclidic, sterility and endotoxins assays. The vials fractionated in mono-doses calibrated for 24 hours showed high stability through freezing and dilution, which allowed the transportation to the Cancer Hospital of Barretos, distant 420 km from the production center in São Paulo. All these mono-doses were administrated to the patients after 24 hours of the production. Also, these results denote that is possible to scale up this production until 74 GBq and be used in a clinical trial that is being planned. Conclusions: These carried out experiments demonstrated that it is possible to produce 177Lu-PSMA-617 for use in clinical trials in Brazil. Until now, four patients are under treatment (compassionate use). Also, these results demonstrate that it is still possible to increase production activity to 74 GBq, just like is normally done with 177Lu-DOTATATE.