[I]-Celecoxib Analogues as SPECT Tracers of Cyclooxygenase-2 in Inflammation.

Abstract

We report the synthesis and evaluation of a series of iodinated celecoxib analogues as cyclooxygenase-2 (COX-2)-targeted single photon emission computerized tomography (SPECT) imaging agents for the detection of inflammation. The structure-activity relationship identified 5-(4-iodophenyl)-1-{4-(methylsulfonyl)phenyl}-3-(trifluoromethyl)-1H-pyrazole (8) as a promising compound with IC(50) values of 0.05 μM against purified COX-2 and 0.03 μM against COX-2 in activated macrophages. The arylstannane of 8 undergoes facile radio-[(123)I]-iodination upon treatment with Na(123)I/NaI and chloramine T using an EtOAc/H(2)O two-phase system. The [(123)I]-8 was produced in a radiochemical yield of 85% and a radiochemical purity of 99%. In vivo SPECT imaging demonstrated that the radiotracer was taken up by inflamed rat paws with an average 1.7-fold enrichment over contralateral noninflamed paws. This study suggests that conversion of celecoxib into its isomeric iodo-[(123)I]-analogues is a useful approach for generating novel and efficacious agents for COX-2-targeted SPECT imaging of inflammation.

• Authors: Md Jashim Uddin, Brenda C Crews, Kebreab Ghebreselasie, Mohammed N Tantawy, Lawrence J Marnett
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 2 Issue 2 Pg. 160-164 (Feb 10 2011) ISSN: 1948-5875 [Print] United States
• PMID: 21318094 (Publication Type: Journal Article)