Obtaining and evaluating the applicability in the treatment of Prostate Cancer of the PSMA-617 kit for prompt radiolabeling with lutetium-177

• Grant number: 18/12965-4
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2018
• End date: November 30, 2020
• Field of knowledge: Engineering - Nuclear Engineering - Applications of Radioisotopes
• Principal Investigator: Elaine Bortoleti de Araújo
• Grantee: Cristian Antonio Wieczorek Villas Boas
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 17/50332-0 - Scientific, technological and infrastructure qualification in radiopharmaceuticals, radiation and entrepreneurship for health purposes (PDIp), AP.PDIP

Abstract

The PSMA is a specific prostatic membrane antigen (glycoprotein type 2) found in the membrane or cytoplasm of the Prostate Cancer cell and has been targeted for treatment of this disease. The discovery of PSMA allowed the creation of novel substances that bind specifically to the antigen and results into more efficient therapies for non-responsive cases, especially of cancer that is not responsive to castration, radiotherapy and chemotherapy, when patient survival is reduced. Currently, there are some antagonists under study, and the most promising results were obtained with PSMA-617.The objective of this project, is to study the radiolabeling parameters of PSMA-617 with lutetium-177 to obtain high specific radiochemical purity and specific activity, evaluate the stability of the radiopharmaceutical and establish the conditions (at therapeutic activity) to transport it without implications on the quality. Chromatographic models (thin layer and High Efficiency Liquid Chromatography) will be tested to evaluate the radiochemical purity of the radiolabelings. Finally, a scale-up study of radiolabeling with activities compatible with radiopharmaceutical production in a manufacturing routine will be conducted. Also the aim of this study is to analyze the therapeutic potential of this radiopharmaceutical with preclinical studies including in vitro tumor cell binding assays and in vivo studies in healthy animals and in animals with a tumor model for Prostate Cancer. The influence of the specific activity of the lutein-177 radionuclide on the efficiency of binding of the radiopharmaceutical to tumor cell receptors will be assessed by in vitro binding studies. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

VILLAS BOAS, CRISTIAN ANTONIO WIECZOREK; SILVA, JEFFERSON DE JESUS; PEREIRA DIAS, LUIS ALBERTO; BRANDAO FREIRE, MARIA RENATA; BALIEIRO, LUIZA MASCARENHAS; FERREIRA DOS SANTOS, CAROLINA SILVA; VIVALDINI, BIANCA FRANCHESQUETI; BENEDETTO, RAQUEL; VIEIRA, DANIEL PEREZ; SOUZA PASSOS, PRISCILA DE QUEIROZ; et al. In vitro and in vivo response of PSMA-617 radiolabeled with CA and NCA lutetium-177. Applied Radiation and Isotopes, v. 180, FEB 2022. (18/12965-4)

VILLAS BOAS, CRISTIAN WIECZOREK; MENGATTI, JAIR; PASSOS, PRISCILA; VIEIRA, DANIEL; DE ARAUJO, ELAINE BORTOLETI. In vitro vitro response of Lu-177-PSMA-617 with two different specific activities. JOURNAL OF NUCLEAR MEDICINE, v. 61, p. 1-pg., 2020-05-01. (18/12965-4)

VILLAS BOAS, CRISTIAN WIECZOREK; SILVA, JEFFERSON DE JESUS; BENEDETTO, RAQUEL; MENGATTI, JAIR; DE ARAUJO, ELAINE BORTOLETI. Lu-177-PSMA-617: Brazilian Experience. JOURNAL OF NUCLEAR MEDICINE, v. 60, p. 1-pg., 2019-05-01. (18/12965-4)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

BOAS, Cristian Antonio Wieczorek Villas. Evaluation of the applicability in prostate cancer of a ready-to-use kit of PSMA-617 for radiolabeled with lutetium-177. 2020. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Pesquisas Energéticas e Nucleares (IPEN/BT) São Paulo.