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

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.