The GLP-1 receptor is expressed in vivo by human metastatic prostate cancer

OBJECTIVES: The glucagon-like peptide 1 (GLP-1) receptor agonist, Liraglutide, reduces human prostate cancer incidence and similar GLP-1 receptor agonists reduce in vitro proliferation and in vivo growth of prostate cancer cell lines. Primary human prostate cancer expresses the GLP-1 receptor (GLP-1R) in vitro. Cancer evolves with stage and whether advanced stage human prostate cancer expresses GLP-1R is unknown. We hypothesised and aimed to prove, that human metastatic castrate resistant prostate cancer (mCRPC) expresses the GLP-1R in vivo. We hypothesised mCRPC would thus be detectable by positron emission tomography/computed tomography (PET/CT) using radiotracer bound to a GLP-1R ligand, as in Exendin PET/CT. DESIGN AND METHODS: Men with mCRPC, with more than one prostate specific membrane antigen (PSMA)-avid lesion on PET/CT scanning (pathognomic in that setting for prostate cancer lesions), were approached to undergo PET/CT with Gallium68-Dota-Exendin-4. We documented PET/CT PSMA-avid lesions which were also PET/CT Exendin-avid as evidence of in vivo GLP-1R expression. RESULTS: Of 24 men referred, three did not meet inclusion criteria. Seventeen declined, largely because the study offered them no therapeutic benefit. Of four men imaged, three had no Exendin-avid lesions, one had six osseous PSMA-avid lesions, three of which were also Exendin-avid. CONCLUSIONS: We demonstrated in vivo GLP-1R expression by human mCPRC, detecting PET/CT lesions avid for both PSMA and Exendin, in one of four participants. GLP-1R expression may thus occur even in advanced stage prostate cancer. Our data contribute to growing evidence supporting the testing of GLP-1 receptor agonists for therapeutic benefit in prostate cancer.