title: Molecular imaging of cyclooxygenase-2 in canine transitional cell carcinomas in vitro and in vivo.
abstract: 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.
authors.affiliation: Department of Small Animal Clinical Sciences, The University of Tennessee, College of Veterinary Medicine, 2407 River Drive A122, Knoxville, TN 37996, USA. mcekanov@utk.edu
authors.forename: Maria
authors.initials: M
authors.lastname: Cekanova
authors.forename: Md Jashim
authors.initials: MJ
authors.lastname: Uddin
authors.forename: Joseph W
authors.initials: JW
authors.lastname: Bartges
authors.forename: Amanda
authors.initials: A
authors.lastname: Callens
authors.forename: Alfred M
authors.initials: AM
authors.lastname: Legendre
authors.forename: Kusum
authors.initials: K
authors.lastname: Rathore
authors.forename: Laura
authors.initials: L
authors.lastname: Wright
authors.forename: Amanda
authors.initials: A
authors.lastname: Carter
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Marnett
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects*; D051546:Cyclooxygenase 2 / Q000737:chemistry / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D003558:Cystoscopy; D004285:Dogs; D005260:Female; D005455:Fluorescent Antibody Technique; D051858:Forkhead Transcription Factors / Q000502:physiology; D064593:Heterografts; D006801:Humans; D007124:Immunoenzyme Techniques; D066298:In Vitro Techniques; D007211:Indoles; D051379:Mice; D008819:Mice, Nude; D061848:Optical Imaging / Q000379:methods*; D012235:Rhodamines; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D051858:Forkhead Transcription Factors; D007211:Indoles; D012235:Rhodamines; C090140:Whn protein; C579286:fluorocoxib A; D051546:Cyclooxygenase 2