Development of PSMA-Targeted Alpha Therapy Using [²¹¹At]PSMA-5.

Area of Science:

• Nuclear Medicine
• Oncology
• Radiopharmaceutical Therapy

Background:

• Astatine-211 (211At) is an alpha-emitting isotope with a suitable half-life for targeted therapies.
• Increasing production of 211At has spurred interest in its therapeutic applications.
• Prostate-specific membrane antigen (PSMA) is a validated target for prostate cancer therapy.

Purpose of the Study:

• To develop and evaluate a novel 211At-labeled PSMA-targeted agent, [211At]PSMA-5.
• To assess the antitumor efficacy and safety of [211At]PSMA-5 in preclinical models.
• To investigate the clinical feasibility and preliminary outcomes of [211At]PSMA-5 in patients with metastatic castration-resistant prostate cancer.

Main Methods:

• Development of a novel 211At-labeled PSMA-targeted agent, [211At]PSMA-5.
• Preclinical evaluation of antitumor efficacy and safety.
• Initiation and conduct of a first-in-human clinical trial in patients with metastatic castration-resistant prostate cancer.

Main Results:

• [211At]PSMA-5 demonstrated high accumulation in recurrent and metastatic lesions in treated patients.
• Nine patients with metastatic castration-resistant prostate cancer have been administered the drug.
• Preliminary data indicate promising localization in target lesions.

Conclusions:

• PSMA-targeted alpha therapy using 211At is a promising treatment modality for prostate cancer.
• Cyclotron-based production, sustainability, and clean decay characteristics support its potential.
• Further clinical evidence and supply chain establishment are necessary for widespread implementation.