²²⁵Ac-PSMA-617 for PSMA targeting alpha-radiation therapy of patients with metastatic castration-resistant prostate cancer

Abstract

Prostate specific membrane antigen (PSMA) is a promising target in prostate cancer. Recently we started the first-in-man treatment with an alpha radionuclide labeled PSMA-ligand. While the case series is still ongoing, here we already report in advance about two patients with metastatic prostate cancer, progressive under multiple therapies and in highly challenging clinical situations, who showed complete responses to therapy with ²²⁵Ac-PSMA-617. Methods: ⁶⁸Ga-PSMA-11 PET/CT validated a PSMA-positive tumor phenotype. Activities of 100 kBq/kg body-weight of ²²⁵Ac-PSMA-617 were administered bi-monthly. PSA response and hematological toxicity were measured at least every four weeks. Restaging was again performed with ⁶⁸Ga-PSMA-11 PET/CT. Results: Both patients experienced a PSA decline below measurable and presented with complete imaging response. No relevant hematological toxicity was observed. Xerostomia was the only mentionable clinical side-effect. Conclusion: Targeted alpha therapy with ²²⁵Ac-PSMA-617, yet experimental, obviously offers a high potential to provide significant benefit to patients in critical condition, e. g. with diffuse red marrow infiltration and resistance against other therapies.