The Value of Gastrin-Releasing Peptide Receptor (GRPR) PET Imaging for Diagnosis and Staging in Prostate Cancer

The gastrin-releasing peptide receptor (GRPR), also known as the bombesin receptor subtype BB2, is a G protein-coupled receptor containing seven transmembrane domains. Its endogenous ligand, gastrin-releasing peptide (GRP), exhibits high homology at the C-terminal peptide sequence with bombesin (BBN), a 14-amino-acid peptide derived from amphibians. GRP regulates a series of physiological processes including cell proliferation, differentiation, and metabolism by activating GRPR and its downstream phospholipase C signaling pathway. Studies have shown that GRPR is highly expressed in various malignant tumors and their metastases, such as gastrinoma (100%), prostate cancer (77%-100%), glioma (85%), gastrointestinal stromal tumors (84%), and breast cancer (62%-71.9%), and is closely associated with tumor growth, invasion, and metastasis. Owing to its widespread and high expression across multiple tumor types, GRPR has emerged as a pan-cancer target of significant clinical value, demonstrating strong potential for applications in the fields of precise tumor diagnosis and targeted therapy. Numerous studies have confirmed that GRPR PET imaging has emerged as a significant molecular imaging modality in prostate cancer, particularly serving as a complementary tool to PSMA PET for addressing cases with negative or insufficient PSMA expression. It demonstrates substantial value in initial staging (especially in intermediate- and high-risk patients), detecting sites of biochemical recurrence, assessing metastatic lesions (notably in mCRPC), and guiding treatment decisions. 68Ga-G21 and 68Ga-G23 are two novel molecular probes targeting GRPR. This study aims to evaluate their biodistribution and diagnostic performance in prostate cancer and compare them with 68Ga-PSMA-11 PET imaging.