title: In vitro and in vivo characterization of novel 18F-labeled bombesin analogues for targeting GRPR-positive tumors.
abstract: The gastrin-releasing peptide receptor (GRPR) is overexpressed on a number of human tumors and has been targeted with radiolabeled bombesin analogues for the diagnosis and therapy of these cancers. Seven bombesin analogues containing various linkers and peptide sequences were designed, synthesized, radiolabeled with (18)F, and characterized in vitro and in vivo as potential PET imaging agents. Binding studies displayed nanomolar binding affinities toward human GRPR for all synthesized bombesin analogues. Two high-affinity peptide candidates 6b (K(i) = 0.7 nM) and 7b (K(i) = 0.1 nM) were chosen for further in vivo evaluation. Both tracers revealed specific uptake in GRPR-expressing PC-3 tumors and the pancreas. Compared to [(18)F]6b, compound [(18)F]7b was characterized by superior tumor uptake, higher specificity of tracer uptake, and more favorable tumor-to-nontarget ratios. In vivo PET imaging allowed for the visualization of PC-3 tumor in nude mice suggesting that [(18)F]7b is a promising PET tracer candidate for the diagnosis of GRPR-positive tumors in humans.
authors.affiliation: Center for Radiopharmaceutical Sciences of ETH, PSI and USZ, Zurich, Switzerland.
authors.forename: Linjing
authors.initials: L
authors.lastname: Mu
authors.forename: Michael
authors.initials: M
authors.lastname: Honer
authors.forename: Jessica
authors.initials: J
authors.lastname: Becaud
authors.forename: Miljen
authors.initials: M
authors.lastname: Martic
authors.forename: Pius A
authors.initials: PA
authors.lastname: Schubiger
authors.forename: Simon M
authors.initials: SM
authors.lastname: Ametamey
authors.forename: Timo
authors.initials: T
authors.lastname: Stellfeld
authors.forename: Keith
authors.initials: K
authors.lastname: Graham
authors.forename: Sandra
authors.initials: S
authors.lastname: Borkowski
authors.forename: Lutz
authors.initials: L
authors.lastname: Lehmann
authors.forename: Ludger
authors.initials: L
authors.lastname: Dinkelborg
authors.forename: Ananth
authors.initials: A
authors.lastname: Srinivasan
mesh_terms: D000818:Animals; D001839:Bombesin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D005462:Fluorine Radioisotopes; D006801:Humans; D008297:Male; D051379:Mice; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology*; D018004:Receptors, Bombesin / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D005462:Fluorine Radioisotopes; D018004:Receptors, Bombesin; D001839:Bombesin