The
enzyme COX-2 is induced at high levels in
tumors but not in surrounding normal tissues, which makes it an attractive target for molecular imaging of
cancer. We evaluated the ability of novel optical imaging agent,
fluorocoxib A to detect urinary bladder canine
transitional cell carcinomas (K9TCC). Here, we show that
fluorocoxib A uptake overlapped with COX-2 expression in primary K9TCC cells in vitro. Using subcutaneously implanted primary K9TCC in athymic mice, we show specific uptake of
fluorocoxib A by COX-2-expressing K9TCC xenograft
tumors in vivo.
Fluorocoxib A uptake by COX-2-expressing xenograft
tumors was blocked by 70% (P < 0.005) when pretreated with the COX-2 selective inhibitor,
celecoxib (10 mg/kg), 4 hours before
intravenous administration of
fluorocoxib A (1 mg/kg).
Fluorocoxib A was taken up by COX-2-expressing
tumors but not by COX-2-negative human UMUC-3 xenograft
tumors. UMUC-3 xenograft
tumors with no expression of COX-2 showed no uptake of
fluorocoxib A. In addition,
fluorocoxib A uptake was evaluated in five dogs diagnosed with TCC.
Fluorocoxib A specifically detected COX-2-expressing K9TCC during cystoscopy in vivo but was not detected in normal urothelium. Taken together, our findings show that
fluorocoxib A selectively bound to COX-2-expressing primary K9TCC cells in vitro, COX-2-expressing K9TCC xenografts
tumors in nude mice, and heterogeneous canine TCC during cystoscopy in vivo. Spontaneous
cancers in companion animals offer a unique translational model for evaluation of novel imaging and therapeutic agents using primary
cancer cells in vitro and in heterogeneous
cancers in vivo.