Assessment of cyclooxygense-2 expression with 99mTc-labeled celebrex

Cyclooxygenase-2 (COX-2) plays an important role in angiogenesis and cancer progression. Since many tumor cells exhibit COX-2 expression, functional imaging of COX-2 expression using celebrex (CBX, a COX-2 inhibitor) may provide not only a non-invasive, reproducible, quantifiable alternative to biopsies, but it also greatly complements pharmacokinetic studies by correlating clinical responses with biological effects. Moreover, molecular endpoints of anti-COX-2 therapy could also be assessed effectively. This study aimed at measuring uptake of 99mTc-EC–CBX in COX-2 expression in tumor-bearing animal models. In vitro Western blot analysis and cellular uptake assays were used to examine the feasibility of using 99mTc-EC–CBX to measure COX-2 activity. Tissue distribution studies of 99mTc-EC–CBX were evaluated in tumor-bearing rodents at 0.5–4 h. Dosimetric absorption was then estimated. Planar scintigraphy was performed in mice, rats and rabbits bearing tumors. In vitro cellular uptake indicated that cells with higher COX-2 expression (A549 and 13762) had higher uptake of 99mTc-EC–CBX than lower COX-2 expression (H226). In vivo biodistribution of 99mTc-EC–CBX in tumor-bearing rodents showed increased tumor:tissue ratios as a function of time. In vitro and biodistribution studies demonstrated the possibility of using 99mTc-EC–CBX to assess COX-2 expression. Planar images confirmed that the tumors could be visualized with 99mTc-EC–CBX from 0.5 to 4 h in tumor-bearing animal models. We conclude that 99mTc-EC–CBX may be useful to assess tumor COX-2 expression. This may be useful in the future for selecting patients for treatment with anti-COX-2 agents.