Bombesin receptor-mediated imaging and cytotoxicity: review and current status

Abstract

The three mammalian bombesin (Bn) receptors (gastrin-releasing peptide [GRP] receptor, neuromedin B [NMB] receptor, BRS-3) are one of the classes of G protein-coupled receptors that are most frequently over-express/ectopically expressed by common, important malignancies. Because of the clinical success of somatostatin receptor-mediated imaging and cytotoxicity with neuroendocrine tumors, there is now increasing interest in pursuing a similar approach with Bn receptors. In the last few years then have been more than 200 studies in this area. In the present paper, the in vitro and in vivo results, as well as results of human studies from many of these studies are reviewed and the current state of Bn receptor-mediated imaging or cytotoxicity is discussed. Both Bn receptor-mediated imaging studies as well as Bn receptor-mediated tumoral cytotoxic studies using radioactive and non-radioactive Bn-based ligands are covered.

Fig. 1

Chemical structure of common linkers used in studies to couple Bombesin (Bn) analogs to various radioisotopes for Bn-receptor-mediated imaging or cytotoxicity. For listing of abbreviations see Table 1.

Fig. 2

Example of usefulness of receptor-mediated imaging for targeting and imaging tumors. The upper panel shows a computed tomographic scan (CT). The lower panel shows the abdominal nuclear medicine images (SPECT image) (from a patient with metastatic neuroendocrine tumor taken 24 hours after injection of 6 mCi of [¹¹¹In-DTPA,DPhe¹]octreotide, to image over-expression of somatostatin receptors on the tumor. In this patient the CT scan was negative, whereas the somatostatin receptor scan was positive for tumor in a number of lymph nodes and the liver. This illustrates the higher sensitivity of somatostatin receptor imaging than conventional imaging (CT, MRI), the precise targeting to the tumor and the clinical usefulness of such an approach.