Evaluation of the applicability in prostate cancer of a ready-to-use kit of PSMA-617 for radiolabeled with lutetium-177

Author(s)

Cristian Antonio Wieczorek Villas Boas

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT)
• Defense date: 2020-11-10

Examining board members

Elaine Bortoleti de Araújo; Carolina Passarelli Gonçalves; Maria Helena Bellini Marumo; Euclides Timoteo da Rocha

• Advisor: Elaine Bortoleti de Araújo

Abstract

Accordingly, to Instituto Nacional do Cancer (INCA) prostate cancer is the second type of malignant disease that most affects men in Brazil. More than 65,000 new cases are expected in 2020. Prostate cancer cells overexpress PSMA, which make it radiopharmaceuticals that specifically bind to PSMA an efficient route for treatment. This work evaluated the effect in vitro and in vivo of two different specific activities of the 177Lu-PSMA-617 based on lutetium-177 route production (with or without carrier added). In addition, the feasibility of production up to 4 therapeutic doses were demonstrated at the scheduling of pilot batches of 177Lu-PSMA-617 (non-carried added). Based on the stability of the therapeutic doses, a prompt kit for radiolabeling was presented in this work. It will be possible to send the radiopharmaceutical to distant regions from the IPEN due to the stability of froze therapeutic doses in a transport package stablished up to 48 hours. The higher specific activity of the radiopharmaceutical showed a lower dissociation constant (Kd value) with statistical significance in the saturation assay. Regardless the specific activity studied, the molar concentration of 177Lu-PSMA-617 was similar in the competition assay. Independent of the specific activity, similar percentages of 177Lu-PSMA-617 were internalized at the internalization assay. Pharmacokinetic and biodistribution profiles were similar, regardless of the specific activity of the radiopharmaceutical. The lower specific activity resulted in a delay in the elimination of 177Lu-PSMA-617 from non-target visceral organs (liver, spleen and pancreas). For both specific activities studied were attested the stability in vivo of 177Lu-PSMA-617, once there was no increase in bone uptake (177LuCl3 has bone tropism). Similar uptakes of 177Lu-PSMA-617 are observed, independent of the specific activity studied, however a better ratio tumor/blood, tissue and specific organs of interest were noticed with the 177Lu-PSMA-617 at the lower specific activity in the biodistribution tumor model. A significant reduction in tumor and renal uptakes of the radiopharmaceutical, for both specific activities, were observed at the in vivo blocking assay. In conclusion, independent of the specific activity of the 177Lu-PSMA-617 studied (with or without carrier added), it was observed similar tumors uptakes. The costs involved in the production of the radiopharmaceutical and the availability of the radioisotope should be used in the choice of lutetium-177 (with or without carrier added). (AU)

• FAPESP's process: 18/12965-4 - Obtaining and evaluating the applicability in the treatment of Prostate Cancer of the PSMA-617 kit for prompt radiolabeling with lutetium-177
• Grantee: Cristian Antonio Wieczorek Villas Boas
• Support Opportunities: Scholarships in Brazil - Doctorate