gallium-68-prostate-specific membrane antigen (PSMA)-11 PET-CT in the diagnosis of prostate cancer

Gallium-68-prostate-specific membrane antigen (PSMA)-11 PET-CT in the diagnosis of prostate cancer

Prostate-specific membrane antigen (PSMA) receptor is overexpressed in most prostate adenocarcinomas, with intra-prostate uptake on PSMA PET-CT correlating with histopathological grade (1):

• Gallium-68 ([⁶⁸Ga]Ga)-PSMA-11 PET-CT is well established for staging prostate cancer for nodal or distant metastatic disease, biochemical recurrence, and eligibility before lutetium-177 PSMA
  
• PRIMARY2 trial confirmed that mpMRI is essential as an initial diagnostic tool for possible prostate cancer with PSMA PET-CT acting as a subsequent filter for patients with inconclusive or negative (PI-RADS 2-3) scans
  • by implementing this imaging-first approach, the trial demonstrated a 49% reduction in unnecessary biopsies while maintaining high accuracy in detecting significant prostate cancer

Notes:

• PSMA, encoded by the FOLH1 gene, is a type II transmembrane glycoprotein composed of 750 amino acid residues, with an extracellular domain comprising approximately 704 amino acids (2)
  • under physiological conditions, PSMA is expressed at low levels in the small intestine, proximal renal tubules, salivary glands, and prostatic epithelium
  • in tumors, PSMA is expressed in the neovasculature of various malignancies; however, its expression is markedly upregulated in both primary and metastatic lesions of prostate cancer and is further elevated in most castration-resistant prostate cancer (CRPC) cases
  • high PSMA expression is positively correlated with a higher Gleason grade and poor prognosis
  • several studies have demonstrated that PSMA expression is associated with the molecular subtypes of metastatic prostate cancer
    • the androgen receptor (AR)-positive subtype generally has high PSMA expression, whereas the AR-negative/neuroendocrine (NE)-positive neuroendocrine subtype often shows low or no PSMA expression (accounting for approximately 15% of cases with CRPC)

Reference:

1. Buteau J et al. Effect of [⁶⁸Ga]Ga-PSMA-11 PET-CT in the diagnosis of prostate cancer in men with equivocal or clinically high-risk non-suspicious findings on multiparametric MRI (PRIMARY2): a multicentre, non-inferiority, phase 3, randomised controlled trial. Lancet Oncology, 2026; 27, 839-848.
2. Ren, X.; Zhang, L.; An, R.; Song, H.; Shi, M.; Wang, Z. Focusing on Prostate-Specific Membrane Antigen in Precision Diagnosis and Treatment of Prostate Cancer. Biomedicines 2026, 14, 482.