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

Three tertiary benzenesulfonamide inhibitors 4a-c were radiolabeled with F-18 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 [F-18]4a-c in CA IX-expressing HT-29 tumours was low without significant contrast. [F-18]4a,b were excreted rapidly, while [F-18]4c exhibited significant in vivo defluorination leading to high bone uptake. Due to minimal uptake in HT-29 tumours compared to normal organs/tissues, F-18-labeled benzenesulfonamides [F-18]4a-c are not suitable as CA IX imaging agents. (C) 2014 Elsevier Ltd. All rights reserved.