Synthesis of bombesin analogues for radiolabeling with rhenium-188

Cancer. 1997 Dec 15;80(12 Suppl):2354-9. doi: 10.1002/(sici)1097-0142(19971215)80:12+<2354::aid-cncr4>;2-j.


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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3T3 Cells
  • Animals
  • Bombesin / analogs & derivatives*
  • Humans
  • Isotope Labeling*
  • Male
  • Mice
  • Neoplasms / radiotherapy*
  • Receptors, Bombesin / antagonists & inhibitors*
  • Rhenium / therapeutic use*


  • Receptors, Bombesin
  • Rhenium
  • Bombesin