GRPR Expression in Metastatic Cancers: A Review of Potential Application of GRPR-Radioligand Therapy
Seminars in Nuclear Medicine. 2025-08-01; :
DOI: 10.1053/j.semnuclmed.2025.07.003
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https://www.bordeaux-neurocampus.fr/11936
Callaud A(1), Duan H(2), Hindié E(3), Morgat C(1), Iagaru A(4).
Author information:
(1)CHU de Bordeaux, Department of Nuclear Medicine & Radiopharmacy, Bordeaux,
France; University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France.
(2)Division of Nuclear Medicine and Molecular Imaging, Department of Radiology,
Stanford University, Stanford, CA.
(3)CHU de Bordeaux, Department of Nuclear Medicine & Radiopharmacy, Bordeaux,
France; University of Bordeaux, CNRS, EPHE, INCIA, UMR 5287, Bordeaux, France;
Institut Universitaire de France, Paris, France.
(4)Division of Nuclear Medicine and Molecular Imaging, Department of Radiology,
Stanford University, Stanford, CA. Electronic address: .
Gastrin-Releasing Peptide Receptor (GRPR) represents a promising molecular
target for radionuclide therapy (TRT) across a variety of malignancies due to
its overexpression in several tumor types, including prostate, breast, lung,
melanoma, cervix, neuroblastoma, head and neck, and colon cancers. While
expression patterns vary-with high GRPR expression notably observed in cervix
and neuroblastoma cancers-tumor heterogeneity and metastatic profiles remain
challenges for patient selection and therapy optimization. Recent advances in
GRPR-targeted radiopharmaceutical development have focused on overcoming peptide
instability and enhancing tumor uptake, exemplified by novel compounds such as
AMTG with improved proteolytic resistance and albumin binding domains to extend
circulatory half-life. Furthermore, innovative radionuclides like terbium-161,
lead-212, copper-67, cobalt-58 m, and arsenic-77 offer enhanced therapeutic
potential beyond the current standard of lutetium-177 through favorable decay
characteristics including Auger electron emission and alpha-particle therapy.
Preclinical and early clinical studies demonstrate encouraging tumor targeting
and therapeutic efficacy with manageable toxicity profiles, particularly in
prostate and cervix cancers. However, further investigation into GRPR expression
heterogeneity, metastatic distribution, and safety is necessary to refine
patient stratification and maximize clinical benefit. This evolving landscape
positions GRPR-TRT as a versatile and potent approach, with the potential to
expand targeted radionuclide therapy to a broader range of malignancies and
improve outcomes in advanced cancers with limited treatment options.
Copyright © 2025 Elsevier Inc. All rights reserved.
DOI: 10.1053/j.semnuclmed.2025.07.003
PMID: 40796452
Conflict of interest statement: Declaration of competing interest Andrei Iagaru
reports scientific advisory board fees from Alpha9Tx, Clarity Pharmaceuticals,
and Radionetics Oncology; research grants from GE HealthCare and Novartis;
consulting fees from GE HealthCare, Novartis, Progenics Pharmaceuticals, and
Telix; and roles on scientific steering committees for Novartis. The remaining
authors declare that they have no known competing financial interests or
personal relationships that could have appeared to influence the work reported
in this paper.