title: Radiolabeling and in vitro and in vivo characterization of [18F]FB-[R(8,15,21), L17]-VIP as a PET imaging agent for tumor overexpressed VIP receptors.
abstract: 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), L17]-VIP peptide for 18F-labeling. This peptide inhibited 125I-VIP binding to rats lung membranes with high affinity [half-maximal inhibitory concentrations (IC50) of 0.12 nm]. Additionally, [R(8,15,21), L17]-VIP showed higher stability than native vasoactive intestinal peptide in vivo of mice. With N-succinimidyl 4-[18F] fluorobenzoate as labeling prosthetic group, [18F]FB-[R(8,15,21), L17]-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/micromol at the end of synthesis. Stability of [18F]FB-[R(8,15,21), L17]-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 [18F]FB-[R(8,15,21), L17]-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. [18F]FB-[R(8,15,21), L17]-VIP has demonstrated its potential for diagnosing tumors overexpressed vasoactive intestinal peptide receptors both in vitro and in vivo.
authors.affiliation: Radiopharmaceuticals Centre, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, 2019 JiaLuo Road, Shanghai 201800, China.
authors.forename: Dengfeng
authors.initials: D
authors.lastname: Cheng
authors.forename: Duanzhi
authors.initials: D
authors.lastname: Yin
authors.forename: Gucai
authors.initials: G
authors.lastname: Li
authors.forename: Mingwei
authors.initials: M
authors.lastname: Wang
authors.forename: Shiqiang
authors.initials: S
authors.lastname: Li
authors.forename: Mingqiang
authors.initials: M
authors.lastname: Zheng
authors.forename: Hancheng
authors.initials: H
authors.lastname: Cai
authors.forename: Yongxian
authors.initials: Y
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry; D015179:Colorectal Neoplasms / Q000737:chemistry; D007457:Iodine Radioisotopes / Q000032:analysis / Q000737:chemistry; D008168:Lung / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000000981:diagnostic imaging*; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000737:chemistry; D051381:Rats; D011919:Rats, Inbred Strains; D018005:Receptors, Vasoactive Intestinal Peptide / Q000032:analysis*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
chemical_list: D007457:Iodine Radioisotopes; D010455:Peptides; D019275:Radiopharmaceuticals; D018005:Receptors, Vasoactive Intestinal Peptide; C518077:vasoactive intestinal peptide, N-succinimidyl 4-fluorobenzoate-Arg(8,15,21)-Leu(17)-; D014660:Vasoactive Intestinal Peptide