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

Chem Biol Drug Des. 2006 Dec;68(6):319-25. doi: 10.1111/j.1747-0285.2006.00453.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Membrane / chemistry
  • Colorectal Neoplasms / chemistry
  • Iodine Radioisotopes / analysis
  • Iodine Radioisotopes / chemistry
  • Lung / chemistry
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Neoplasms / diagnostic imaging*
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Positron-Emission Tomography*
  • Radiopharmaceuticals* / chemical synthesis
  • Radiopharmaceuticals* / chemistry
  • Rats
  • Rats, Inbred Strains
  • Receptors, Vasoactive Intestinal Peptide / analysis*
  • Vasoactive Intestinal Peptide / analogs & derivatives*
  • Vasoactive Intestinal Peptide / chemical synthesis
  • Vasoactive Intestinal Peptide / chemistry


  • Iodine Radioisotopes
  • Peptides
  • Radiopharmaceuticals
  • Receptors, Vasoactive Intestinal Peptide
  • vasoactive intestinal peptide, N-succinimidyl 4-fluorobenzoate-Arg(8,15,21)-Leu(17)-
  • Vasoactive Intestinal Peptide