Synthesis and evaluation of (18)F-labeled tertiary benzenesulfonamides for imaging carbonic anhydrase IX expression in tumours with positron emission tomography

Bioorg Med Chem Lett. 2014 Jul 15;24(14):3064-8. doi: 10.1016/j.bmcl.2014.05.021. Epub 2014 May 17.

Abstract

Three tertiary benzenesulfonamide inhibitors 4a-c were radiolabeled with (18)F and evaluated for imaging carbonic anhydrase IX (CA IX) expression with positron emission tomography. All three inhibitors exhibit <10 nM affinity for CA IX with no measurable affinity for CA II. Despite good affinity/selectivity to CA IX and excellent stability in plasma, uptake of [(18)F]4a-c in CA IX-expressing HT-29 tumours was low without significant contrast. [(18)F]4a,b were excreted rapidly, while [(18)F]4c exhibited significant in vivo defluorination leading to high bone uptake. Due to minimal uptake in HT-29 tumours compared to normal organs/tissues, (18)F-labeled benzenesulfonamides [(18)F]4a-c are not suitable as CA IX imaging agents.

Keywords: Carbonic anhydrase IX; Fluorine-18; In vivo defluorination; Positron emission tomography; Tertiary benzenesulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Neoplasm / analysis*
  • Antigens, Neoplasm / metabolism
  • Benzenesulfonamides
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / analysis*
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / metabolism
  • Carbonic Anhydrase Inhibitors / pharmacokinetics
  • Carbonic Anhydrases / analysis*
  • Carbonic Anhydrases / metabolism
  • Fluorine Radioisotopes
  • HT29 Cells
  • Humans
  • Mice
  • Molecular Imaging
  • Neoplasms, Experimental / enzymology*
  • Neoplasms, Experimental / metabolism
  • Positron-Emission Tomography*
  • Sulfonamides / analysis*
  • Sulfonamides / chemistry*
  • Sulfonamides / metabolism
  • Sulfonamides / pharmacokinetics

Substances

  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • Fluorine Radioisotopes
  • Sulfonamides
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases