An Update of Radiolabeled Bombesin Analogs for Gastrin-Releasing Peptide Receptor Targeting

Abstract

Prostate cancer is a critical public health problem in USA and Europe. New non-invasive imaging methods are urgently needed, due to the low accuracy and specificity of current screen methods and the desire of localizing primary prostate cancer and bone metastasis. Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) are the non-invasive and sensitive imaging methods which have been widely used for diagnosing diseases in the clinic. Lack of suitable radiotracers is the major issue for nuclear imaging of prostate cancer, although radiolabeled bombesin (BN) peptides targeting the Gastrin-Releasing Peptide Receptor (GRPR) on tumor cells are widely investigated. In this review we discuss the recent trends in the development of GRPR-targeted radiopharmaceuticals based on BN analogs with regard to their potential for imaging and therapy of GRPR-expressing malignancies. Following a brief introduction of GRPR and bombesin peptides, we summarize the properties of prostate cancer specific radiolabeled bombesins. New bombesin tracers published in the last five years are reviewed and compared according to their novelties in biomolecules, radionuclides, labeling methods, bifunctional chelators and linkers. Hot topics such as multimerization, application of agonists and antagonists are highlighted in the review. Lastly, a few clinical trials of cancer nuclear imaging with radiolabeled bombesin have been discussed.

Theranostic Perspectives in Prostate Cancer with the Gastrin-Releasing Peptide Receptor Antagonist NeoBOMB1: Preclinical and First Clinical Results

“…The first-generation radiopeptides developed for such purposes were GRPR agonists derived from C-terminal fragments of the amphibian tetradecapeptide bombesin (BBN) (7)(8)(9)(10)(11)(12) or the respective human 27mer peptide GRP (13)(14)(15). The use of resulting radioligands in humans was soon linked to undesirable effects after agonist-induced GRPR activation (16).…”

68Ga/177Lu-NeoBOMB1, a Novel Radiolabeled GRPR Antagonist for Theranostic Use in Oncology

“…After the successful use of radiolabeled somatostatin peptide analogs in neuroendocrine tumors for nuclear imaging and therapy (5,6), multiple radiolabeled GRPR radioligands have been synthesized and studied in preclinical as well as in clinical studies, mostly in prostate cancer patients. Examples of such peptide analogs include AMBA, the Demobesin series, and MP2653 (7)(8)(9)(10)(11). Recent studies have shown a preference for GRPR antagonists compared with GRPR agonists (12,13).…”

“…The peptidic part of NeoBOMB1, however, is based on a different GRPR antagonist first described by Heimbrook et al (17) and generated by modification of the C-terminal Leu 13 -Met 14 -NH 2 and the replacement of Asn 6 by DPhe 6 of native bombesin (6)(7)(8)(9)(10)(11)(12)(13)(14). NeoBOMB1 was chosen for further studies because of its improved affinity for the GRPR (18,19).…”

Bombesin-Targeted PET of Prostate Cancer

“…In this review, we discuss the preclinical and clinical work already done or under evaluation for the use of gastrin-releasing peptide receptors (GRPRs) as targets for the imaging of PC, with a focus on the development of PET tracers for the imaging of GRPRpositive tumors. Comprehensive recent reviews have discussed tracers for use in SPECT and therapy (2,3).…”