Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study

J Med Chem. 2005 Jan 13;48(1):100-10. doi: 10.1021/jm049437y.


Four open chain tetraamine-functionalized bombesin (BB) analogues were synthesized [parent tetradecapeptide-based Demobesin 3 and 4 and BB(7-14)-based Demobesin 5 and 6]. Labeling with (99m)Tc afforded high-purity and high specific activity radiotracers. Peptides showed high affinity for the human GRP-R (GRP-R = gastrin releasing peptide receptor) expressed in PC-3 cells. In human tumors preferentially expressing single bombesin receptor subtypes, they showed high affinity for the GRP-R, less affinity for the NMB-R (NMB-R = neuromedin B receptor) and no affinity for the orphan BB(3)-R (bombesin subtype 3 receptor). [(99m)Tc]Demobesin 3-6 efficiently internalized in a time- and dose-dependent manner in PC-3 cells and showed a high and specific uptake in human PC-3 xenografts and the pancreas of nude mice. [(99m)Tc]Demobesin 3 and 4 were rapidly excreted via the kidneys while the truncated analogues were predominantly processed by the hepatobiliary system. Patient studies are scheduled for validating the suitability of [(99m)Tc]Demobesin 3 and 4 in the GRP-R-targeted imaging of tumors.

MeSH terms

  • Animals
  • Autoradiography / methods
  • Biopsy
  • Bombesin / analogs & derivatives*
  • Drug Evaluation, Preclinical / methods
  • Female
  • Humans
  • Isotope Labeling / methods
  • Male
  • Metabolic Clearance Rate
  • Mice
  • Mice, Nude
  • Prostatic Neoplasms / diagnostic imaging*
  • Prostatic Neoplasms / metabolism
  • Radionuclide Imaging
  • Radiopharmaceuticals* / chemistry
  • Radiopharmaceuticals* / pharmacokinetics
  • Receptors, Bombesin / metabolism*
  • Technetium* / chemistry
  • Tissue Distribution
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays


  • Radiopharmaceuticals
  • Receptors, Bombesin
  • Technetium
  • Bombesin