title: Potent bombesin-like peptides for GRP-receptor targeting of tumors with 99mTc: a preclinical study.
abstract: 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.
authors.affiliation: Institute of Radioisotopes-Radiodiagnostic Products, National Center for Scientific Research Demokritos, 15310 Athens, Greece.
authors.forename: Berthold A
authors.initials: BA
authors.lastname: Nock
authors.forename: Anastasia
authors.initials: A
authors.lastname: Nikolopoulou
authors.forename: Athanassios
authors.initials: A
authors.lastname: Galanis
authors.forename: Paul
authors.initials: P
authors.lastname: Cordopatis
authors.forename: Beatrice
authors.initials: B
authors.lastname: Waser
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Reubi
authors.forename: Theodosia
authors.initials: T
authors.lastname: Maina
mesh_terms: D000818:Animals; D001345:Autoradiography / Q000379:methods; D001706:Biopsy; D001839:Bombesin / Q000031:analogs & derivatives*; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D018004:Receptors, Bombesin / Q000378:metabolism*; D013667:Technetium / Q000737:chemistry; D014018:Tissue Distribution; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D019275:Radiopharmaceuticals; D018004:Receptors, Bombesin; D013667:Technetium; D001839:Bombesin