F-18-AmBF3-MJ9: A novel radiofluorinated bombesin derivative for prostate cancer imaging

A novel radiofluorinated derivative of bombesin, F-18-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 (K-i = 0.5 +/- 0.1 nM). The F-18-labeling was performed via a facile one-step F-18-F-19 isotope exchange reaction, and F-18-AmBF3-MJ9 was obtained in 23 +/- 5% (n = 3) radiochemical yield in 25 min with >99% radiochemical purity and 100 +/- 32 GBq/lmol specific activity. F-18-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 F-18-AmBF3-MJ9 by GRPR-expressing pancreas and PC-3 prostate cancer xenografts. Tumor uptake was 1.37 +/- 0.25%ID/g at 1 h, and 2.20 +/- 0.13% ID/g at 2 h 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 F-18-AmBF3-MJ9 is a promising PET tracer for imaging GRPR-expressing prostate cancers. (C) 2015 The Authors. Published by Elsevier Ltd.