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


Uddin MJMd Jashim , Vemulapalli AAnoop , Niitsu HHiroaki , Crews BCBrenda C , Oltman CGConnor G , Kingsley PJPhilip J , Kavanaugh TETaylor E , Bedingfield SKSean K , Mcintyre JOJ Oliver , Milad MMatthew , Aleem AMAnsari M , Coffey RJRobert J , Duvall CLCraig L , Marnett LJLawrence J . ACS medicinal chemistry letters. 2020 2 24; 11(10). 1875-1880


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.