In-DOTA-Gly-benzoyl-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH

The amphibian bombesin (BBN or BN, a peptide of 14 amino acids) is an analog of human gastrin-releasing peptide (GRP, a peptide of 27 amino acids) that binds to GRP receptors (GRPR) with high affinity and specificity (1). Both GRP and BBN share an amidated C-terminus sequence homology of seven amino acids, Trp-Ala-Val-Gly-His-Leu-Met-NH. BBN-Like peptides have been shown to induce various biological responses in diverse tissues, including the central nervous system (CNS) and the gastrointestinal (GI) system. They also act as potential growth factors for both normal and neoplastic tissues (2). Specific BBN receptors (BBN-R) have been identified on CNS and GI tissuesincluding the pancreas and on a number of tumor cell lines. The BBN-R superfamily includes at least four different subtypes, namely neuromedin B (NMB or BB1), the GRPR subtype (BB2), the BB3 subtype, and the BB4 subtype (3). The findings of GRPR overexpression in various human tumors, such as breast, prostate, lung, colon, ovarian, and pancreatic cancers, provide opportunities for tumor imaging by designing specific molecular imaging agents to target the GRPR. Currently used targeting GRPR peptides mainly are agonists. Therefore, there is a need for GRPR antagonist radioligands. Llinares et al. (4) has developed a series of GRPR peptide antagonists. One of them, D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH (RM26), was found to be a selective GRPR antagonist. DOTA-Gly-benzoyl group was added to the C-terminus to form DOTA-Gly-benzoyl-D-Phe-Gln-Trp-Ala-Val-Gly-His-Sta-Leu-NH (RM1). For evaluation as a single-photon emission computed tomography (SPECT) imaging agent for GRPR, In has been attached to RM1 to form In-RM1 (5).