BACKGROUND: Gastrin-releasing peptide receptors (GRPR) are overexpressed in small cell lung carcinoma and some other human cancers. Small molecule peptides with antagonistic activities toward these receptors are potential radiotherapeutic agents. METHODS: A 7-amino acid analogue of bombesin (BBN) was synthesized through solid-phase techniques. The peptide was conjugated to trisuccin prior to cleavage from the resin. The conjugate was hydrogenated to remove the hydroxamate-protecting benzyl groups followed by purification through reversed-phase high performance liquid chromatography (RP-HPLC). Rhenium-188 (188Re)-labeling of the trisuccin-peptide conjugate was performed by a SnCl2-reduced radioisotope and the labeled product was purified by RP-HPLC. The labeled conjugate was incubated with BNR-11 (3T3 mouse fibroblast cells stably transfected with murine GRPR) and PC-3 human prostate carcinoma GRPR positive cells. The nonradioactive peptide analogue was used as a competitive inhibitor and 125I-[Tyr4]-BBN was used as a positive control. RESULTS: Solid-phase and solution phase synthesis afforded the conjugates of the hydroxamate ligand trisuccin with the 7-amino acid BBN analogue. The molecules differed by either a direct attachment of the trisuccin to the peptide (TrisBBN) or connection through a 6-carbon linker (TrisC6BBN). The overall yield for each synthesis was approximately 20%. Both conjugates showed the correct molecular weights on mass spectroscopy. Radiolabeling of the conjugates with 188Re were performed in > or = 90% yield. Cell-binding assays performed with BNR-11 (TrisBBN and TrisC6BBN) and PC-3 (TrisBBN) cell lines resulted in positive binding. CONCLUSIONS: The synthesis and radiolabeling of Tris-BBN conjugates with 188Re were shown to be feasible. The yields of chemical syntheses and radiolabeling and positive binding of the radiolabeled conjugates to GRPR-positive tumor cells reveal promise in the use of these molecules for cancer imaging and therapy. More work is needed and is in progress to optimize the cell-binding properties.