title: (18)F-AmBF3-MJ9: a novel radiofluorinated bombesin derivative for prostate cancer imaging.
abstract: A novel radiofluorinated derivative of bombesin, (18)F-AmBF3-MJ9, was synthesized and evaluated for its potential to image prostate cancer by targeting the gastrin releasing peptide receptor (GRPR). AmBF3-MJ9 was prepared from an ammoniomethyl-trifluoroborate (AmBF3) conjugated alkyne 2 and azidoacetyl-MJ9 via a copper-catalyzed click reaction, and had good binding affinity for GRPR (Ki=0.5±0.1nM). The (18)F-labeling was performed via a facile one-step (18)F-(19)F isotope exchange reaction, and (18)F-AmBF3-MJ9 was obtained in 23±5% (n=3) radiochemical yield in 25min with >99% radiochemical purity and 100±32GBq/μmol specific activity. (18)F-AmBF3-MJ9 was stable in mouse plasma, and was partially (22-30%) internalized after binding to GRPR. Positron emission tomography (PET) imaging and biodistribution studies in mice showed fast renal excretion and good uptake of (18)F-AmBF3-MJ9 by GRPR-expressing pancreas and PC-3 prostate cancer xenografts. Tumor uptake was 1.37±0.25%ID/g at 1h, and 2.20±0.13%ID/g at 2h post-injection (p.i.) with low background uptake and excellent tumor visualization (tumor-to-muscle ratios of 75.4±5.5). These data suggest that (18)F-AmBF3-MJ9 is a promising PET tracer for imaging GRPR-expressing prostate cancers.
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Maral
authors.initials: M
authors.lastname: Pourghiasian
authors.affiliation: Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Jinhe
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada.
authors.forename: Nadine
authors.initials: N
authors.lastname: Colpo
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada; Department of Radiology, University of British Columbia, 3350-950 West 10th Avenue, Vancouver, British Columbia V5Z 4E3, Canada.
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
authors.affiliation: Chemistry Department, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada. Electronic address: dperrin@chem.ubc.ca.
authors.forename: David M
authors.initials: DM
authors.lastname: Perrin
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Vancouver, British Columbia V5Z 1L3, Canada; Department of Radiology, University of British Columbia, 3350-950 West 10th Avenue, Vancouver, British Columbia V5Z 4E3, Canada. Electronic address: fbenard@bccrc.ca.
authors.forename: François
authors.initials: F
authors.lastname: Bénard
mesh_terms: D000818:Animals; D001839:Bombesin / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D005462:Fluorine Radioisotopes / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D049268:Positron-Emission Tomography / Q000379:methods; D011471:Prostatic Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism; D014057:Tomography, X-Ray Computed / Q000379:methods
chemical_list: D005462:Fluorine Radioisotopes; D001839:Bombesin
keywords: (18)F-labeling; AmBF(3)-MJ9; GRP receptors; Prostate cancer