Discovery of carbon-11 labeled sulfonamide derivative: A PET tracer for imaging brain NLRP3 inflammasome

Bioorg Med Chem Lett. 2021 Feb 15:34:127777. doi: 10.1016/j.bmcl.2021.127777. Epub 2021 Jan 6.

Abstract

We report herein the discovery of a positron emission tomography (PET) tracer for the (NOD)-like receptor protein 3 (NLRP3). Our recent medicinal chemistry campaign on developing sulfonamide-based NLRP3 inhibitors led to an analog, 1, with a methoxy substituent amenable to labeling with carbon-11. PET/CT imaging studies indicated that [11C]1 exhibited rapid blood-brain barrier (BBB) penetration and moderate brain uptake, as well as blockable uptake in the brain. [11C]1, thus suggesting the potential to serve as a useful tool for imaging NLRP3 inflammasome in living brains.

Keywords: Blockable uptake; Blood-brain barrier (BBB) penetration; NLRP3; Positron emission tomography (PET); Sulfonamide derivative.

Publication types

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

MeSH terms

  • Animals
  • Blood-Brain Barrier / metabolism
  • Carbon Radioisotopes
  • Drug Discovery*
  • Inflammasomes / analysis*
  • Inflammasomes / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Molecular Structure
  • NLR Family, Pyrin Domain-Containing 3 Protein / analysis*
  • NLR Family, Pyrin Domain-Containing 3 Protein / metabolism
  • Positron Emission Tomography Computed Tomography*
  • Radiopharmaceuticals / chemical synthesis
  • Radiopharmaceuticals / chemistry*
  • Radiopharmaceuticals / metabolism
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism

Substances

  • Carbon Radioisotopes
  • Carbon-11
  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Radiopharmaceuticals
  • Sulfonamides