Multicenter program using PSMA radioligants for the diagnosis and therapy of patients with prostate cancer

• Grant number: 20/07065-4
• Support Opportunities: Research Grants - Problem-Oriented Research Centers in São Paulo
• Start date: September 01, 2023
• End date: August 31, 2028
• Field of knowledge: Engineering - Nuclear Engineering - Applications of Radioisotopes
• Principal Investigator: Wilson Aparecido Parejo Calvo
• Grantee: Wilson Aparecido Parejo Calvo
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil
• Pesquisadores principais: Carlos Alberto Buchpiguel ; Emerson Soares Bernardes ; Luiz Juliano Neto ; Rui Manuel Vieira Reis
• Associated researchers: Alexandre Keiji Tashima ; André Zelanis Palitot Pereira ; Bárbara Juarez Amorim ; Carlos Alberto Zeituni ; Carolina Meloni Vicente ; Catarina Segreti Porto ; Celso Darío Ramos ; Denise Maria Zezell ; Efrain Araujo Perini ; Elaine Bortoleti de Araújo ; Elba Cristina Sá de Camargo Etchebehere ; Euclides Timoteo da Rocha ; Evelinda Marramon Trindade ; Flavio Mavignier Cárcano ; Ileana Gabriela Sánchez de Rubió ; Isolda Costa ; Jair Mengatti ; José Barreto Campello Carvalheira ; Lorena Pozzo ; Luciane Sussuchi da Silva ; Lucilena Rebelo Monteiro ; Ludmila Santiago Almeida ; Luis Eduardo Rosa Zucca ; Manoel João Batista Castello Girão ; Marcelo Tatit Sapienza ; Marcus V. Sadi ; Maria Aparecida Juliano ; Maria Elisa Chuery Martins Rostelato ; Mariana da Cunha Lopes de Lima ; Mayara Aguilar Dias de Brito ; Mércia Liane de Oliveira ; Ricardo Pimenta Bertolla ; Rodrigo Esaki Tamura ; Ubirajara Ferreira ; Wagner Eduardo Matheus ; Wilson Eduardo Furlan Matos Alves

Abstract

Prostate cancer is the second leading cause of male cancer mortality in Brazil. In recent years, prostate-specific membrane antigen (PSMA)-targeted radioligand therapy has emerged as a promising option for patients suffering from mCRPC and do not respond to previously recommended therapies. Indeed, 45-60% of patients with mCRPC respond to 177Lu-PSMA therapy as demonstrated by several clinical studies conducted worldwide. However, 177Lu-PSMA therapy is still not accessible to Brazilian patients who have exhausted all therapeutic option. Recently, it has been shown that treatment with 225Ac-PSMA can be an effective alternative for the approximately 30% of patients who don't respond to 177Lu-PSMA. However, the molecular features of the subgroup of patients with poor response to 177Lu-PSMA is still not known, nor the characteristics that would make these patients sensitive to 225Ac-PSMA. Therefore, this Interdisciplinary and Interinstitutional Research group aims to expand the therapeutic alternatives for cancer patients who are not responsive to currently available treatments in the São Paulo State Department of Health (SES/SP) and Brazilian Unified Health System (SUS), through the introduction of cutting-edge therapeutic radiopharmaceuticals, 177Lu-PSMA and 225Ac-PSMA. In addition, we aim to identify and characterize the genomic, proteomic and metabolomic features in tumor and liquid biopsies from patients unresponsive to 177Lu-PSMA therapy. To achieve these goals, the Energy and Nuclear Research Institute (IPEN-CNEN/SP), a pioneer institution in the production of radiopharmaceuticals in Brazil, will produce 177Lu-PSMA and 225Ac-PSMA and all radiopharmaceuticals needed for cancer diagnosis and follow-up, which will be distributed among network partners including, the Cancer Institute of the State of São Paulo, /Hospital das Clínicas of São Paulo/ The University of São Paulo Medical School (ICESP/HC/FMUSP), the Federal University of São Paulo (UNIFESP), the University of Campinas (UNICAMP) and the Barretos Cancer Hospital (HCB). These institutions will be responsible for the selection, treatment with 177Lu/225Ac-PSMA and for monitoring of patients with mCRPC as well as the genetic and molecular characterization of unresponsive patients. We expect this project would bring us the opportunity to offer a cutting-edge therapeutic option to patients with mCRPC in the state of São Paulo and, at the same time, to discover potential prognostic biomarkers in 177Lu/225Ac-PSMA unresponsive patients. (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)

RODRIGUES, P. S.; BURIN, A. L.; TALACIMON, C. F.; MEDEIROS, I. M. M. A.; PEREIRA, J. J. N.; TEODORO, L. E. H.; RIGO, M. E. Z.; GESSERAME, M. M. F.; TAVARES, P. V. S.; MARTINS, A. C.; et al. Investigation for Monte Carlo simulation with geometric simplification of the GammaCell 220 irradiator with experimental measurements using Fricke xylenol gel (FXG). Radiation Physics and Chemistry, v. 224, p. 6-pg., 2024-08-21. (17/50332-0, 20/07065-4)

MOTTA, GUACYARA; JULIANO, LUIZ; CHAGAS, JAIR RIBEIRO. Human plasma kallikrein: roles in coagulation, fibrinolysis, inflammation pathways, and beyond. FRONTIERS IN PHYSIOLOGY, v. 14, p. 12-pg., 2023-08-30. (20/07065-4)

EL HAJJ, LARA; BURIN, ANA LAURA; TALACIMON, CRISTHIAN FERREIRA; MEDEIROS, ILCA MARLI MOITINHO AMARAL; RIGO, MARIA EDUARDA ZAGANIN; TAVARES, PAULO VICTOR DOS SANTOS; RODRIGUES, PRISCILA SANTOS; NOGUEIRA, THUANY CORREA; ROSERO, WILMMER ALEXANDER ARCOS; RODRIGUES JR, ORLANDO; et al. Using a Monte Carlo simulation to analyze the ideal activity for a phosphorus-32 polymeric brachytherapy source for paraspinal tumors. Radiation Physics and Chemistry, v. 224, p. 4-pg., 2024-08-21. (17/50332-0, 20/07065-4)