Synthesis of carbon-11 labeled celecoxib derivatives as new candidate PET radioligands for imaging of inflammation

Abstract

Cyclooxygenase (prostaglandin endoperoxide synthase or COX) enzyme represents a particularly attractive target in inflammation processes for the development of both therapeutic agents and imaging agents. This study was designed to develop new radioligands for imaging of inflammation using the biomedical imaging technique positron emission tomography (PET). Carbon-11 labeled celecoxib derivatives, [ 11C]methyl 2-(4-(5- p-tolyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl)phenylsulfonamidooxy)acetate ([ 11C] 6e), [ 11C]methyl 2-methyl-2-(4-(5- p-tolyl-3-(trifluoromethyl)-1 H-pyrazol-1-yl)phenylsulfonamidooxy)propanoate ([ 11C] 6f), [ 11C]methyl 2-(4-(5-(4-methoxyphenyl)-3-(trifluoromethyl)-1 H-pyrazol-1-yl)phenylsulfonamidooxy)acetate ([ 11C] 6g), and [ 11C]methyl 2-methyl-2-(4-(5-(4-methoxyphenyl)-3-(trifluoromethyl)-1 H-pyrazol-1-yl)phenylsulfonamidooxy)propanoate ([ 11C] 6h), were prepared by O-[ 11C]methylation of their corresponding precursors using [ 11C]CH 3OTf under basic condition and isolated by a simplified solid-phase extraction (SPE) method in 50–60% radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 15–20 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 111–185 GBq/μmol.