Premium
Radiolabeling and in vitro and in vivo Characterization of [ 18 F]FB‐[R 8,15,21 , L 17 ]‐VIP as a PET Imaging Agent for Tumor Overexpressed VIP Receptors
Author(s) -
Cheng Dengfeng,
Yin Duanzhi,
Li Gucai,
Wang Mingwei,
Li Shiqiang,
Zheng Mingqiang,
Cai Hancheng,
Wang Yongxian
Publication year - 2006
Publication title -
chemical biology and drug design
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.59
H-Index - 77
eISSN - 1747-0285
pISSN - 1747-0277
DOI - 10.1111/j.1747-0285.2006.00453.x
Subject(s) - biodistribution , vasoactive intestinal peptide , in vivo , peptide , chemistry , in vitro , receptor , microbiology and biotechnology , biochemistry , biology , neuropeptide
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 8,15,21 , L 17 ]‐VIP peptide for 18 F‐labeling. This peptide inhibited 125 I‐VIP binding to rats lung membranes with high affinity [half‐maximal inhibitory concentrations (IC 50 ) of 0.12 n m ]. Additionally, [R 8,15,21 , L 17 ]‐VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N ‐succinimidyl 4‐[ 18 F] fluorobenzoate as labeling prosthetic group, [ 18 F]FB‐[R 8,15,21 , 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/ μ mol at the end of synthesis. Stability of [ 18 F]FB‐[R 8,15,21 , 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 [ 18 F]FB‐[R 8,15,21 , 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. [ 18 F]FB‐[R 8,15,21 , L 17 ]‐VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo .