The gastrin-releasing peptide receptor in oncology: a comprehensive review of recent advances in targeted radionuclide theranostics

This is the authors' abstract. We don't add key points for this paper.

The gastrin-releasing peptide receptor (GRPR) is aberrantly expressed in several malignancies, including prostate cancer, breast cancer, lung cancer, and gastrointestinal stromal tumors, making it an important target for molecular imaging and targeted radionuclide therapy. In recent years, advances in radioligand design, radionuclide selection, and theranostic concepts have substantially promoted the development of GRPR-mediated oncologic applications in nuclear medicine. This review systematically summarizes recent progress in GRPR-targeted radioligands for tumor imaging and radioligand therapy, with particular emphasis on their biological rationale, representative tracers, clinical utility, and major limitations across different tumor types. Overall, GRPR-targeted imaging has demonstrated promising diagnostic value in prostate cancer, estrogen receptor-positive breast cancer, and selected gastrointestinal stromal tumors, and may complement existing imaging modalities. From a therapeutic perspective, the development of high-stability antagonists, metabolic protection strategies, and novel therapeutic radionuclides is driving GRPR-targeted radioligand therapy toward improved therapeutic index and greater translational potential. Nevertheless, several challenges remain, including receptor heterogeneity, physiologic uptake in normal tissues, optimization of pharmacokinetics, the complexity of dual-targeted constructs, and the lack of high-quality prospective clinical evidence. Future progress will likely depend on ligand engineering, dual-target strategies, individualized dosimetry, and the integration of imaging-based treatment assessment into a closed-loop precision theranostic framework.