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Updated: Oct 3, 2025

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

Sashi Debnath1, Ning Zhou1, Mark McLaughlin2

  • 1Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.

International Journal of Molecular Sciences
|February 15, 2022
PubMed
Summary

Researchers are developing advanced prostate-specific membrane antigen (PSMA) agents for prostate cancer imaging and therapy. Chemical modifications aim to improve drug delivery, targeting accuracy, and reduce side effects for better patient outcomes.

Keywords:
binding affinityinhibitorpositron emission tomographyprostate cancerprostate-specific antigenprostate-specific membrane antigenradionuclide therapytheranostics

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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.