In an effort to develop a peptide-based radiopharmaceutical for the detection of tumors overexpressed vasoactive intestinal peptide receptors with positron emission tomography, we have prepared a novel [R-8,R-15,R-21, L-17]-VIP peptide for F-18-labeling. This peptide inhibited I-125-VIP binding to rats lung membranes with high affinity [half-maximal inhibitory concentrations (IC50) of 0.12 nM]. Additionally, [R-8,R-15,R-21, L-17]-VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N-succinimidyl 4-[F-18] fluorobenzoate as labeling prosthetic group, [F-18]FB-[R-8,R-15,R-21, L-17]-VIP was obtained in > 99% radiochemical purity within 100 min in decay-for-corrected radiochemical yield of 33.6 +/- 3% (n = 5) and a specific radioactivity 255 GBq/mu mol at the end of synthesis. Stability of [F-18]FB-[R-8,R-15,R-21, L-17]-VIP in vitro and in vivo were investigated. Biodistribution of this trace was carried out in mice with induced C26 colorectal tumor. Fast clearance of [F-18]FB-[R-8,R-15,R-21, L-17]-VIP from non-target tissues and specific uptakes by tumors realized higher tumor-to-muscle ratio (3.55) and tumor-to-blood ratio (2.37) 60 min postinjection. Clear difference was observed between the blocking and unblocking experiments in biodistribution and whole body radioautography. [F-18]FB-[R-8,R-15,R-21, L-17]-VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.
