title: 2-Fluoropyridine prosthetic compounds for the 18F labeling of bombesin analogues.
abstract: Acetylene-bearing 2-[(18)F]fluoropyridines [(18)F]FPy5yne and PEG-[(18)F]FPyKYNE were prepared via efficient nucleophilic heteroaromatic [(18)F]fluorination of their corresponding 2-trimethylammoniumpyrdinyl precursors. The prosthetic groups were conjugated to azide- and PEG3-modified bombesin(6-14) analogues via copper-catalyzed azide-alkyne cycloaddition couplings to yield mono- and di-mini-PEGylated ligands for PET imaging of the gastrin- releasing peptide receptor. The PEG3- and PEG2/PEG3-bearing (18)F peptides showed decreased lipophilicity relative to an analogous non-mini-PEGylated (18)F peptide. Assessment of water-soluble peptide pharmacokinetics and tumour-targeting capabilities in a mouse model of prostate cancer is currently underway.
authors.affiliation: TRIUMF, Nuclear Medicine Division, 4004 Wesbrook Mall, Vancouver, Canada BC V6T 2A3. james_inkster@alumni.sfu.ca
authors.forename: James
authors.initials: J
authors.lastname: Inkster
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.forename: Samia
authors.initials: S
authors.lastname: Ait-Mohand
authors.forename: Simon
authors.initials: S
authors.lastname: Gosselin
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.forename: Brigitte
authors.initials: B
authors.lastname: Guérin
authors.forename: Maral
authors.initials: M
authors.lastname: Pourghiasian
authors.forename: Thomas
authors.initials: T
authors.lastname: Ruth
authors.forename: Paul
authors.initials: P
authors.lastname: Schaffer
authors.forename: Tim
authors.initials: T
authors.lastname: Storr
mesh_terms: D000818:Animals; D001839:Bombesin / Q000138:chemical synthesis / Q000737:chemistry; D004195:Disease Models, Animal; D005462:Fluorine Radioisotopes / Q000737:chemistry; D008024:Ligands; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009374:Neoplasms, Experimental / Q000175:diagnosis*; D049268:Positron-Emission Tomography; D011471:Prostatic Neoplasms / Q000175:diagnosis*; D011725:Pyridines / Q000737:chemistry; D018004:Receptors, Bombesin / Q000032:analysis*
chemical_list: C521930:2-fluoropyridine; D005462:Fluorine Radioisotopes; D008024:Ligands; D011725:Pyridines; D018004:Receptors, Bombesin; D001839:Bombesin