Enabling Efficient Positron Emission Tomography (PET) Imaging of Synaptic Vesicle Glycoprotein 2A (SV2A) with a Robust and One-Step Radiosynthesis of a Highly Potent 18F-Labeled Ligand ([18F]UCB-H)

J Med Chem. 2016 Oct 13;59(19):8955-8966. doi: 10.1021/acs.jmedchem.6b00905. Epub 2016 Sep 20.

Abstract

We herein describe the straightforward synthesis of a stable pyridyl(4-methoxyphenyl)iodonium salt and its [18F] radiolabeling within a one-step, fully automated and cGMP compliant radiosynthesis of [18F]UCB-H ([18F]7), a PET tracer for the imaging of synaptic vesicle glycoprotein 2A (SV2A). Over the course of 1 year, 50 automated productions provided 34 ± 2% of injectable [18F]7 from up to 285 GBq (7.7 Ci) of [18F]fluoride in 50 min (uncorrected radiochemical yield, specific activity of 815 ± 185 GBq/μmol). The successful implementation of our synthetic strategy within routine, high-activity, and cGMP productions attests to its practicality and reliability for the production of large doses of [18F]7. In addition to enabling efficient and cost-effective clinical research on a range of neurological pathologies through the imaging of SV2A, this work further demonstrates the real value of iodonium salts for the cGMP 18F-PET tracer manufacturing industry, and their ability to fulfill practical and regulatory requirements in that field.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorine Radioisotopes / chemistry*
  • Male
  • Membrane Glycoproteins / analysis*
  • Models, Molecular
  • Nerve Tissue Proteins / analysis*
  • Positron-Emission Tomography / methods*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyrrolidinones / chemical synthesis
  • Pyrrolidinones / chemistry*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Fluorine Radioisotopes
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Pyridines
  • Pyrrolidinones
  • Sv2a protein, rat
  • UCB-H compound