GLP-1 Receptor Found on Metastatic Prostate Cancer in Living Patients for the First Time

One of four patients with mCRPC had three bone metastases that were positive for both PSMA (confirming prostate cancer) and gallium-68-DOTA-exendin-4 (confirming GLP-1R expression). This is the first in vivo demonstration of GLP-1R expression in metastatic prostate cancer. The patient had six PSMA-avid lesions, three of which were also exendin-avid.

Pilot imaging study. Men with mCRPC and multiple PSMA-avid PET/CT lesions underwent additional PET/CT with gallium-68-DOTA-exendin-4 (a GLP-1R-targeting radiotracer). Dual-positive lesions (PSMA+ and exendin+) confirmed in vivo GLP-1R expression by metastatic prostate cancer.

If prostate cancer expresses GLP-1 receptors, then the millions of men taking GLP-1 drugs for diabetes or obesity might already be receiving some anti-cancer benefit. It also opens the door to using GLP-1 receptor agonists as targeted cancer therapy or for GLP-1R-targeted imaging to guide treatment decisions in prostate cancer.

The relationship between metabolic hormones and cancer is increasingly recognized. GLP-1's presence on prostate cancer opens multiple therapeutic possibilities — from repurposing existing GLP-1 drugs as anti-cancer agents to developing GLP-1R-targeted theranostics (combined imaging and therapy). This is particularly significant given the enormous overlap between the diabetes/obesity population and prostate cancer risk population.

Extremely small sample — only 4 patients were imaged, and 17 declined participation (the study offered no therapeutic benefit). Only 1 of 4 patients showed GLP-1R expression, and not all lesions in that patient were positive, suggesting heterogeneous expression. The GLP-1R-positive rate cannot be estimated from 4 patients. The radiotracer's sensitivity may be limited.