Development of alpha particle emitting radionuclide therapy according to GMP guidelines for treatment of mCRPC

Currently, prostate cancer patients are treated with hormone therapy and chemotherapy. However, for patients that are diagnosed with advanced stage prostate cancer, mCPRC, effective treatment is lacking. Recently, interests have grown in the field of nuclear medicine towards a therapeutic radionuclide linked to PSMA for the treatment of mCPRC, in analogy to for example 177Lu-labelled PSMA-I&T and PSMA-617 [1, 2]. Furthermore, the alpha emitting radionuclide Ac-225 surfaced as a candidate radionuclide for targeted alpha-particle therapy (TAT) due to the preferable characteristics regarding high LET energies, deposit of the energy at a close range and an appropriate half-life for treatment (T1/2 = 9.92 days). Consequently, high-energy ionizing radiation is delivered to the mCPRC cells specifically, causing double strand breaks. [225Ac]Ac-PSMA-I&T emerged as a possible effective treatment of mCPRC[3]. The aim of this study is to manufacture [225Ac]Ac-PSMA-I&T according to GMP guidelines for the translation of [225Ac]Ac-PSMA-I&T (8-12 MBq) into the clinic for a phase 1 dose escalation study. For diagnostic inclusion, a [68Ga]Ga-PSMA-I&T scan is anticipated.

HOOIJMAN Eline;  CHALASHKAN Yozlem;  LING S W;  KAHYARGIL Figen;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  SEIMBILLE Yann;  KOOLEN Stijn;  BRABANDER Tessa;  DE BLOIS Erik; 

2022-03-28

ELSEVIER SCIENCE INC

JRC124539

0969-8051 (online),   

https://www.sciencedirect.com/science/article/pii/S0969805121003012,    https://publications.jrc.ec.europa.eu/repository/handle/JRC124539,   

10.1016/S0969-8051(21)00301-2 (online),