METHODS.
A 7-amino acid analogue of bombesin (BBN) was synthesized through solid-phase techniques. The peptide was conjugated to trisuccin prior to cleavage 1 Department of Radiation Oncology, University from the resin. The conjugate was hydrogenated to remove the hydroxamateof Alabama at Birmingham, Birmingham, Alaprotecting benzyl groups followed by purification through reversed-phase high bama.
performance liquid chromatography (RP-HPLC). Rhenium-188 ( 188 Re)-labeling of 2 Department of Medicine, University of Alathe trisuccin-peptide conjugate was performed by a SnCl 2 -reduced radioisotope bama at Birmingham, Birmingham, Alabama.
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 125 I-[Tyr 4 ]-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 188 Re were performed in Β’ 90% yield. Cell-binding assays performed with BNR-11 (TrisBBN and TrisC6BBN) and PC-3 (TrisBBN) cell lines resulted in positive binding. Presented at the Sixth Conference on Radioimmunodetection and Radioimmunotherapy of CONCLUSIONS. The synthesis and radiolabeling of Tris-BBN conjugates with 188 Re Cancer, Princeton, New Jersey, October 10-12, were shown to be feasible. The yields of chemical syntheses and radiolabeling and 1996.
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