Prostate cancer was the most frequently diagnosed cancer in men in 112 countries around the world in 2020, with 1.4 million newly diagnosed cases leading to more than 375,000 deaths [1]. The open-label, multi-center, randomized phase 3 VISION study (NCT03511664) demonstrated the efficacy and safety of 177Lu-PSMA-617 targeted radioligand therapy in patients with progressive prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) [2].

Metastatic castration-resistant prostate cancer (mCRPC) has a very bad prognosis with most patients dying within two years of diagnosis [1]. Available therapies for mCRPC are often associated with poor tissue selectivity, and side effects including high systemic toxicity and drug resistance.

PSMA (prostate-specific membrane antigen) is a glycoprotein highly expressed on the surface of malignant prostate tumor cells. Thus, it represents a suitable target for both imaging and therapy of prostate cancer (PCa). In fact, PSMA ligands are widely used either as tracers for positron emission tomography/computed tomography (PET/CT) imaging or as therapeutic agents comprising PSMA-directed radionuclide therapy and immunotherapy [1].

The positive efficacy and safety data of 177Lu-PSMA-617 in the treatment of mCRPC patients from the Lu-PSMA and VISION trials led to its FDA approval and designation as a breakthrough therapy for later lines of mCRPC treatment [1,2]. 223Ra-dichloride (223RaCl2) is a targeted α-therapy and prolongs OS in patients with bone-predominant mCRPC [3].