Synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer

The enzyme cyclooxygenase-2 (COX-2) is overexpressed in a variety of malignant tumors. This study was designed to develop new radiotracers for imaging of COX-2 in cancer using biomedical imaging technique positron emission tomography (PET). Carbon-11-labeled celecoxib derivatives, [ 11C] 4a– c and [ 11C] 8a– d, were prepared by O-[ 11C] methylation of their corresponding precursors using [ 11C]CH 3OTf under basic conditions and isolated by a simplified solid-phase extraction (SPE) method in 52 ± 2% ( n = 5) and 57 ± 3% ( n = 5) radiochemical yields based on [ 11C]CO 2 and decay corrected to end of bombardment (EOB). The overall synthesis time from EOB was 23 min, the radiochemical purity was >99%, and the specific activity at end of synthesis (EOS) was 277.5 ± 92.5 GBq/μmol ( n = 5). The IC 50 values to block COX-2 for known compounds celecoxib ( 4d), 4a and 4c were 40, 290 and 8 nM, respectively, and preliminary findings from in vitro biological assay indicated that the synthesized new compounds 4b and 8a– d display similar strong inhibitory effectiveness in the MDA-MB-435 human cancer cell line in comparison with the parent compound 4d. These results encourage further in vivo evaluation of carbon-11-labeled celecoxib derivatives as new potential PET radiotracers for imaging of COX-2 expression in cancer. This paper reports the synthesis and preliminary in vitro biological evaluation of new carbon-11-labeled celecoxib derivatives as candidate PET tracers for imaging of COX-2 expression in cancer. [Display omitted] ► Celecoxib and its new derivatives have been designed and synthesized. ► Carbon-11 labeled celecoxib derivatives have been synthesized as new PET tracers. ► New compounds display similar strong inhibitory potencies compared to celecoxib.