title: 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.
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Rm 4-123, Vancouver, BC V5Z1L3, Canada.
authors.forename: Joseph
authors.initials: J
authors.lastname: Lau
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Rm 4-123, Vancouver, BC V5Z1L3, Canada.
authors.forename: Jinhe
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Rm 4-123, Vancouver, BC V5Z1L3, Canada.
authors.forename: Zhengxing
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Rm 4-123, Vancouver, BC V5Z1L3, Canada.
authors.forename: Navjit
authors.initials: N
authors.lastname: Hundal-Jabal
authors.affiliation: Department of Chemistry, University of British Columbia, Vancouver, BC V6T1Z1, Canada.
authors.forename: Zhibo
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Rm 4-123, Vancouver, BC V5Z1L3, Canada.
authors.forename: François
authors.initials: F
authors.lastname: Bénard
authors.affiliation: Department of Molecular Oncology, BC Cancer Agency, 675 West 10th Avenue, Rm 4-123, Vancouver, BC V5Z1L3, Canada. Electronic address: klin@bccrc.ca.
authors.forename: Kuo-Shyan
authors.initials: KS
authors.lastname: Lin
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000032:analysis* / Q000378:metabolism; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D002256:Carbonic Anhydrases / Q000032:analysis* / Q000378:metabolism; D005462:Fluorine Radioisotopes; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D057054:Molecular Imaging; D009374:Neoplasms, Experimental / Q000201:enzymology* / Q000378:metabolism; D049268:Positron-Emission Tomography; D013449:Sulfonamides / Q000032:analysis* / Q000737:chemistry* / Q000378:metabolism / Q000493:pharmacokinetics; D000096926:Benzenesulfonamides
chemical_list: D000951:Antigens, Neoplasm; D000071231:Carbonic Anhydrase IX; D002257:Carbonic Anhydrase Inhibitors; D002256:Carbonic Anhydrases; D005462:Fluorine Radioisotopes; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C089226:CA9 protein, human
keywords: Carbonic anhydrase IX; Fluorine-18; In vivo defluorination; Positron emission tomography; Tertiary benzenesulfonamides