PSMA-based alpha therapy in prostate cancer

Metastatic castration-resistant prostate cancer (mCRPC) remains a highly fatal disease despite the widespread utilization of both the established and novel agents acting on different pathways, including taxane-based chemotherapy, next-generation anti-androgen, and radionuclide therapy with Radium dichloride [1-3].Recent evidence demonstrate radioligand therapy with lutetium-177prostate-specific membrane antigen [177Lu]Lu-PSMA) as a paradigm-changing treatment for a prostate cancer as however a significant proportion of patients may still not respond to this treatment [1]. Hence amongst several potential strategies of optimizing radioligand therapy is the use of alpha-emitting radionuclides with deposition of a sizable amount of energy within a short radius resulting in effective tumoral cytotoxicity and sparing of the normal organs. Additionally, the alpha-emitting radionuclides possess a high linear energy transfer of alpha particles that causes direct double-stranded deoxyribonucleic acid (DNA) damage and DNA cluster breaks independently from the cell cycle phase or tissue oxygenation [3]. Based on these advantages there is arguably greater potential to overcome resistance to PRLT with beta-emitting radionuclide or treatment with chemotherapeutic drugs. Furthermore, the short radius could enable the design of a rational combinatorial approach to treatment by targeting different tumor pathways.

SATHEKGE Mike;  MORGENSTERN Alfred; 

2023-12-13

SPRINGER

JRC134721

1619-7070 (online),   

https://link.springer.com/article/10.1007/s00259-023-06384-0,    https://publications.jrc.ec.europa.eu/repository/handle/JRC134721,   

10.1007/s00259-023-06384-0 (online),