Synthesis and evaluation of -[F] fluorocelecoxib for COX-2 cholangiocarcinoma imaging.

BACKGROUND

An F-tagged NSAID analog was prepared for use as a probe for COX-2 expression, which is associated with tumor development.

METHODS

The in vivo uptake of celecoxib was monitored with -[F]fluorocelecoxib using positron emission tomography (PET). The binding affinity of -[F]fluorocelecoxib to COX-1 and COX-2 enzymes were assessed using the competitor celecoxib.

RESULTS

The IC values were 0.039 μM and 0.024 μM, respectively. A selectivity index of 1.63 was obtained (COX-2 vs COX-1). COX-2 overexpressed cholangiocarcinoma (CCA) murine cells took up more -[F]fluorocelecoxib than that by usual CCA cells from 10 to 60 minutes post incubation. Competitive inhibition (blocking) of the tracer uptake of -[F]fluorocelecoxib in the presence of celecoxib by the COX-2 overexpressed CCA cells and the usual CCA cells gave the IC values of 0.5 μM and 46.5 μM, respectively. Based on the in vitro accumulation data and in vivo metabolism half-life (30 min), PET scanning was performed 30-60 min after the administration of -[F]fluorocelecoxib through the tail vein. Study of -[F]F-celecoxib in the CCA rats showed a tumor to normal ratio (T/N) of 1.38±0.23 and uptake dose of 1.14±0.25 (%ID/g).

CONCLUSION

The inferior in vivo blocking results of 1.48±0.20 (T/N) and 1.18±0.22 (%ID/g) suggests that the nonspecificity is associated with the complex role of peroxidase or the binding to carbonic anhydrase.