Molecular Imaging of Inflammation in Osteoarthritis Using a Water-Soluble Fluorocoxib

Authors

Uddin MJ Md Jashim , Vemulapalli A Anoop , Niitsu H Hiroaki , Crews BC Brenda C , Oltman CG Connor G , Kingsley PJ Philip J , Kavanaugh TE Taylor E , Bedingfield SK Sean K , Mcintyre JO J Oliver , Milad M Matthew , Aleem AM Ansari M , Coffey RJ Robert J , Duvall CL Craig L , Marnett LJ Lawrence J .
ACS medicinal chemistry letters. 2020 2 24; 11(10).
1875-1880

Abstract

Clinical imaging approaches to detect inflammatory biomarkers, such as cyclooxygenase-2 (COX-2), may facilitate the diagnosis and therapy of inflammatory diseases. To this end, we report the discovery of -[(rhodamin-X-yl)but-4-yl]-2-[1-(4-chlorobenzoyl)-5-methoxy-2-methyl-1-indol-3-yl]acetamide chloride salt (fluorocoxib D), a hydrophilic analog of fluorocoxib A. Fluorocoxib D inhibits COX-2 selectively in purified enzyme preparations and cells. It exhibits adequate photophysical properties to enable detection of COX-2 in intact cells, in a mouse model of carrageenan-induced acute footpad inflammation and inflammation in a mouse model of osteoarthritis. COX-2-selectivity was verified either by blocking the enzyme’s active site with celecoxib or by molecular imaging with nontargeted 5-carboxy-X-rhodamine dye. These data indicate that fluorocoxib D is an ideal candidate for early detection of inflammatory or neoplastic lesions expressing elevated levels of COX-2.