Prostate-Specific Membrane Antigen Biology and Pathophysiology in Prostate Carcinoma, an Update: Potential Implications for Targeted Imaging and Therapy

Int J Mol Sci. 2024 Sep 9;25(17):9755. doi: 10.3390/ijms25179755.

Abstract

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein, was shown to be expressed 100-1000 fold higher in prostate adenocarcinoma as compared to normal prostate epithelium. Given the enzymatic function of PSMA with the presence of an internalization triggering motif, various Glu-urea-Lys-based inhibitors have been developed and, amongst others, radiolabeled with positron emitters for targeted positron emission tomography imaging such as 68Ga-PSMA-HBED-CC Glu-urea-Lys(Ahx) as well as with beta and alpha-emitting radioisotopes for targeted therapy, e.g., 177Lu-PSMA-617. In this paper, we review and discuss the potential implications for targeted imaging and therapy of altered PSMA-glycosylation, of PSMA-driven activation of the P13K/Akt/mTOR, of the evolution over time and the relationship with androgen signaling and changes in DNA methylation of PSMA, and of androgen deprivation therapy (ADT) in prostate carcinoma.

Keywords: PSMA-pathophysiology-targeted; imaging and therapy.

Publication types

  • Review

MeSH terms

  • Antigens, Surface* / metabolism
  • Glutamate Carboxypeptidase II* / metabolism
  • Glycosylation
  • Humans
  • Male
  • Molecular Targeted Therapy / methods
  • Positron-Emission Tomography / methods
  • Prostatic Neoplasms* / diagnostic imaging
  • Prostatic Neoplasms* / drug therapy
  • Prostatic Neoplasms* / metabolism
  • Prostatic Neoplasms* / pathology
  • Prostatic Neoplasms* / therapy

Substances

  • Glutamate Carboxypeptidase II
  • FOLH1 protein, human
  • Antigens, Surface

Grants and funding

This research received no external funding.