PSMA theranostics

Last revised by Khalid Alhusseiny on 14 Jul 2023

PSMA theranostics is an emerging nuclear medicine approach in the management of prostate cancer that combines the use of prostate-specific membrane antigen (PSMA)-targeted imaging and therapy 1. PSMA-targeted imaging can be used to identify and locate prostate cancer cells, while PSMA radioligand (or radionuclide) therapy delivers radiation to these targets.

The prostate-specific membrane antigen (PSMA) is a transmembrane protein that has upregulated expression on the surface of approximately 95% of prostate cancer cells 2. This makes it an attractive target for the development of new diagnostic and therapeutic agents.

PSMA imaging facilitates patient selection for PSMA-targeted radioligand therapy and provides information on the localization and extent of PSMA-expressing lesions. Currently, PSMA theranostics is primarily indicated for the treatment of patients with metastatic castration-resistant prostate cancer 1,3. PSMA theranostics can also be used to treat patients with locally advanced prostate cancer who are not eligible for surgery or local radiotherapy.

PSMA theranostics involves two main steps 4,6:

  1. PSMA imaging: fluorodeoxyglucose (FDG) PET/CT or SPECT imaging with intravenous administration of radiolabeled PSMA ligand (commonly 68Ga-PSMA-aa or 18F-DCFPyL)

  2. PSMA-targeted radioligand therapy: therapeutic radioligands (177Lu or 225Ac) bound to PSMA ligands administered; these radioligands emit beta particles (177Lu) or alpha particles (225Ac), delivering localized radiation to PSMA-expressing tumor cells while sparing other tissue; response my be monitored through follow-up PSMA imaging

Although generally well tolerated, patients may experience radioligand-induced toxicity including myelosuppression and xerostomia 5. Patients may also experience allergic reactions to radiotracers.

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