Evaluation of the tolerability and safety of [225Ac]Ac-PSMA-I&T in patients with metastatic prostate cancer: a phase I dose escalation study

Life expectancy of patients with metastatic castration-resistant prostate cancer (mCRPC) is still limited despite several systemic treatments. Within five years after diagnosis of primary prostate cancer, 10–20% of the patients have mCRPC and curation is not an option. Radionuclide therapy (RNT) targeted against prostate-specific membrane antigen (PSMA) emerged as a new treatment option and showed effective results in patients with mCRPC. Survival benefit after [177Lu]Lu-PSMA RNT has already been demonstrated in several clinical trials. However, [225Ac]Ac-PSMA (225Ac-PSMA) appears to be an even more promising radiopharmaceutical for the treatment of mCRPC. The use of alpha emitting radionuclides offers advantages over beta emitting radionuclides due to the high linear energy transfer effective for killing tumor cells and the limited range to reduce the radiation effects on the healthy tissue. However, these results are based on retrospective data and safety data of 225Ac-PSMA are still limited. Therefore, a prospective trial is needed to determine the optimal amount of activity that can be administered.

LING Sui Wai;  VAN DER VELDT Astrid;  KONIJNENBERG M.W.;  SEGBERS Marcel;  HOOIJMAN Eline;  BRUCHERTSEIFER Frank;  MORGENSTERN Alfred;  DE BLOIS Erik;  BRABANDER Tessa; 

2024-09-05

BMC

JRC138940

1471-2407 (online),   

https://bmccancer.biomedcentral.com/articles/10.1186/s12885-024-11900-y,    https://publications.jrc.ec.europa.eu/repository/handle/JRC138940,   

10.1186/s12885-024-11900-y (online),