[11C]BCTC: Radiosynthesis and in vivo binding to transient receptor potential vanilloid subfamily member 1 (TRPV1) receptor in the mouse trigeminal nerve

Bioorg Med Chem Lett. 2017 Oct 1;27(19):4521-4524. doi: 10.1016/j.bmcl.2017.08.061. Epub 2017 Sep 1.

Abstract

The purpose of this study was to synthesize a new positron emission tomography radiotracer, N-(4-tertiarybutylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-[11C]carboxamide ([11C]BCTC, [11C]1), and assess its in vivo binding to the transient receptor potential vanilloid subfamily member 1 (TRPV1) receptor in mice. [11C]BCTC was synthesized by reacting the hydrochloride of 4-tertiarybutylaniline (2·HCl) with [11C]phosgene ([11C]COCl2) to give isocyanate [11C]4, followed by reaction with 4-(3-chloropyridin-2-yl)tetrahydropyrazine (3). [11C]BCTC was obtained at a 16-20% radiochemical yield, based on the cyclotron-produced [11C]CO2 (decay-corrected to the end of bombardment), with >98% radiochemical purity and 65-110GBq/μmol specific activity at the end of synthesis. An ex vivo biodistribution study in mice confirmed the specific binding of [11C]BCTC to TRPV1 in the trigeminal nerve, which is a tissue with high TRPV1 expression.

Keywords: Capsaicin; Positron emission tomography; TRPV1; Transient receptor potential vanilloid subfamily member 1; Trigeminal nerve; [(11)C]BCTC; [(11)C]phosgene.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Carbon Isotopes
  • Dose-Response Relationship, Drug
  • Mice
  • Mice, Inbred Strains
  • Molecular Structure
  • Positron-Emission Tomography
  • Pyrazines / chemical synthesis
  • Pyrazines / chemistry
  • Pyrazines / pharmacokinetics*
  • Pyridines / chemical synthesis
  • Pyridines / chemistry
  • Pyridines / pharmacokinetics*
  • Radioactive Tracers
  • Structure-Activity Relationship
  • TRPV Cation Channels / biosynthesis
  • TRPV Cation Channels / chemistry*
  • Tissue Distribution
  • Trigeminal Nerve / chemistry*

Substances

  • Carbon Isotopes
  • N-(4-tert-butylphenyl)-4-(3-chloropyridin-2-yl)tetrahydropyrazine-1(2H)-carboxamide
  • Pyrazines
  • Pyridines
  • Radioactive Tracers
  • TRPV Cation Channels
  • TRPV1 receptor