Prostate Cancer, Part 2: PSMA and Beyond.

Area of Science:

• Oncology
• Nuclear Medicine
• Radiopharmaceutical Chemistry

Background:

• Prostate-specific membrane antigen (PSMA) has transformed prostate cancer management.
• PSMA-targeted agents offer a theranostic link between imaging and radionuclide therapy.

Purpose of the Study:

• To review PSMA biology and radiopharmaceutical performance.
• To discuss emerging strategies for PSMA-directed theranostics.
• To explore next-generation approaches for prostate cancer treatment.

Main Methods:

• Review of contemporary PSMA PET agents and radioligand therapy.
• Analysis of chelator chemistry, linker design, and binding sites.
• Discussion of emerging radionuclides, ligand engineering, and multi-target agents.

Main Results:

• ¹⁷⁷Lu-PSMA-617 demonstrates improved survival in metastatic castration-resistant prostate cancer.
• ²²⁵Ac-PSMA offers potential for micrometastatic and radioresistant disease but faces challenges.
• Ligand engineering and novel radionuclides aim to enhance tumor retention and theranostic pairing.

Conclusions:

• PSMA theranostics are evolving beyond a single-target approach.
• Personalized radioligand selection and sequencing are crucial for optimal outcomes.
• Future strategies will broaden molecular targets to address disease heterogeneity.