Evaluation of the stability and biodistribution of a clinical formulation of 177Lu-PSMA for prostate cancer

• Grant number: 20/04480-0
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: November 01, 2020
• End date: October 31, 2024
• Field of knowledge: Health Sciences - Medicine - Medical Radiology
• Principal Investigator: Mariana Ramos Fernandes Camacho
• Grantee: Mariana Ramos Fernandes Camacho
• Company: Medicina Nuclear de Campinas Ltda
• CNAE: Atividades de atenção ambulatorial executadas por médicos e odontólogos ; Atividades de serviços de complementação diagnóstica e terapêutica
• City: Campinas
• Associated researchers: Aline Biggi Mattiolli ; Flaviane Aparecida da Silva

Abstract

Prostate cancer is a neoplasm of high incidence, prevalence and mortality in the world and many patients develop metastatic disease that becomes resistant to conventional antiandrogen therapies. Such patients are classified as having metastatic castration resistant prostate cancer (mCPRC). At this stage of the disease, there are few therapeutic options, and the survival of these patients is low. Recently, a new form of treatment of these patients has been developed. The method is based on the fact that malignant prostatic neoplastic prostate tissue has increased expression of the prostate specific membrane antigen (PSMA) and when radiolabeled it is able to bind to the sites affected by the disease. This PSMA can be radiolabeled with radioisotopes with therapeutic action (such as lutetium-177). In this PIPE Phase II project, we intend to continue the PIPE Phase I project. In Phase I (2017/15575-0) of the project, we developed the labeling of the PSMA with lutetium-177 (PSMA-177Lu) and started the tests to develop the lyophilized kit containing the ready to use PSMA for radiolabeling with 177Lu. In Phase I of this project, we evaluated the various parameters of quality control in order to ensure reproducibility in the manufacturing and radiolabeling processes of the PSMA-177Lu in the in-house and kit models and we continued the tests for product development in kit format. Since we have ascertained the safety of the radiolabeling of this tracer, in the present study we intend to evaluate the stability of the PSMA-177Lu kit. We will evaluate the stability in mice and posteriorly, in mCRPC patients we will verify if the biodistribution pattern remains similar to that obtained in the animal model, as it is known that there are biodistribution differences among the species. The main objectives of this PIPE Phase II project are to assess whether the lyophilized kit remains stable in adverse environmental conditions to ensure proper radiolabeling and distribution and evaluate if the PSMA-177Lu kit presents, in humans, the same biodistribution as in animals. (AU)