A 18F-labeled saxitoxin derivative for in vivo PET-MR imaging of voltage-gated sodium channel expression following nerve injury

J Am Chem Soc. 2013 Dec 4;135(48):18012-5. doi: 10.1021/ja408300e. Epub 2013 Nov 21.

Abstract

Both chronic and neuropathic pain conditions are associated with increased expression of certain voltage-gated sodium ion channel (NaV) isoforms in peripheral sensory neurons. A method for noninvasive imaging of these channels could represent a powerful tool for investigating aberrant expression of NaV and its role in pain pathogenesis. Herein, we describe the synthesis and evaluation of a positron emission tomography (PET) radiotracer targeting NaVs, the design of which is based on the potent, NaV-selective inhibitor saxitoxin. Both autoradiography analysis of sciatic nerves excised from injured rats as well as whole animal PET-MR imaging demonstrate that a systemically administered [(18)F]-labeled saxitoxin derivative concentrates at the site of nerve injury, consistent with upregulated sodium channel expression following axotomy. This type of PET agent has potential use for serial monitoring of channel expression levels at injured nerves throughout wound healing and/or following drug treatment. Such information may be correlated with pain behavioral analyses to help shed light on the complex molecular processes that underlie pain sensation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Fluorine Radioisotopes / chemistry
  • Magnetic Resonance Imaging
  • Neuralgia / diagnosis*
  • Neuralgia / metabolism
  • Positron-Emission Tomography
  • Rats
  • Saxitoxin / analogs & derivatives*
  • Saxitoxin / chemical synthesis
  • Sciatic Nerve / injuries*
  • Sciatic Nerve / metabolism
  • Voltage-Gated Sodium Channel Blockers / chemical synthesis
  • Voltage-Gated Sodium Channel Blockers / chemistry*
  • Voltage-Gated Sodium Channels / analysis*
  • Voltage-Gated Sodium Channels / metabolism

Substances

  • Fluorine Radioisotopes
  • Voltage-Gated Sodium Channel Blockers
  • Voltage-Gated Sodium Channels
  • Saxitoxin