PSMA-Targeting Imaging and Theranostic Agents-Current Status and Future Perspective

Area of Science:

• Oncology
• Radiochemistry
• Pharmacology

Background:

• Prostate-specific membrane antigen (PSMA) targeted agents have advanced significantly for prostate cancer (PCa) diagnosis and treatment.
• Recent US-FDA approvals of [⁶⁸Ga]Ga-PSMA-11 and [¹⁸F]F-DCFPyL for PET imaging mark progress in clinical application.
• PSMA-targeted agents are crucial for identifying PCa metastases and recurrence.

Purpose of the Study:

• To review the historical development of PSMA-targeting agents for prostate cancer.
• To provide an overview of current advancements in PSMA-targeted imaging and theranostics.
• To highlight future directions focusing on chemical modifications for next-generation agents.

Main Methods:

• Literature review of PSMA-targeting agents development.
• Analysis of chemical modification strategies for improved pharmacokinetics and binding affinity.
• Focus on structural determinants influencing agent efficacy and safety.

Main Results:

• PSMA-inhibitor-derived agents are now in clinical practice and trials for prostate cancer.
• Current research focuses on enhancing in vivo pharmacokinetics and target binding affinity.
• Chemical modifications of linkage moieties are key strategies for next-generation agents.

Conclusions:

• PSMA-targeted agents represent a significant advancement in prostate cancer management.
• Future developments aim to increase detection sensitivity/specificity and minimize off-target toxicity, especially renal.
• Structural modifications are critical for optimizing the performance of future PSMA-targeting agents.