Gastrin-releasing peptide receptor (GRPR)

Gastrin-releasing peptide

Gastrin-releasing peptide (GRP) contains 27 amino acids, and belongs to the family of bombesin-like peptides (BLPs). GRP was initially isolated from porcine stomach. BLPs have wide variety of physiological functions, for instance in fetal development, cell differentiation, and glucose homeostasis. GRP is found in peripheral nervous system and in the GI tract, and it is synthesized by many tumour types. GRP is bound to specific G protein coupled receptors, which also are overexpressed in many cancer types.


Bombesin (BBN) contains 14 amino acids, and is a homologue to the mammalian GRP, with high similarity in the C-terminal part. Bombesin was originally isolated from the skin of the toad Bombina bombina. Bombesin contains C-terminal carboxyamide.

In mammals, BBN binds to three G-protein coupled receptors: neuromedin B receptor (BB1R), gastrin-releasing peptide receptor (BB2R or GRPR), and orphan receptor (BB3R). Bombesin binding, and subsequent internalization, activates these receptors, which stimulates the release of hormones such as gastrin and somatostatin, and smooth muscle contraction in the GI tract. In tumours the activation stimulates cell proliferation, and BBN receptors are often upregulated in for example breast cancer, prostate cancer, glioblastoma, pancreatic cancer, lung carcinomas, and cancers of the GI tract. Therefore, bombesin-derived radioligands have been developed and studied for imaging cancer. Bombesin and bombesin antagonist derivatives for PET imaging include [68Ga]BZH3 (Schuhmacher et al., 2005; Dimitrakopoulou-Strauss et al., 2011), [68Ga]AMBA (Cagnolini et al., 2010; Schroeder et al., 2011; Prignon et al., 2015), [68Ga]NOTA-P2-RM26 and [11F]AlF-NOTA-P2-RM26 (Varasteh et al., 2013a and 2013b), [68Ga]RM2 (or [68Ga]BAY86-7548) (Mansi et al., 2011; Roivainen et al., 2013; Kähkönen et al., 2013; Stoykow et al., 2016; Minamimoto et al., 2016 and 2018), and [68Ga]SB3 (Maina et al., 2016).

See also:


Baratto L, Jadvar H, Iagaru A. Prostate cancer theranostics targeting gastrin-releasing peptide receptors. Mol Imaging Biol. 2017; 20: 501-509. doi: 10.1007/s11307-017-1151-1.

Ferreira CA, Fuscaldi LL, Townsend DM, Rubello D, de Barros ALB. Radiolabeled bombesin derivatives for preclinical oncological imaging. Biomed Pharmacother. 2017; 87: 58-72. doi: 10.1016/j.biopha.2016.12.083.

Varasteh Z. Bombesin antagonists for targeting gastrin-releasing peptide receptor-positive tumors. Design, synthesis, preclinical evaluation and optimization of imaging agents. Acta Universitatis Upsaliensis, 2014. Thesis.

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Created at: 2018-09-15
Updated at: 2018-09-25
Written by: Vesa Oikonen