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Detection of overexpressed COX-2 in precancerous lesions of hamster pancreas and lungs by molecular imaging: implications for early diagnosis and prevention
ChemMedChem (2006)
  • Hildegard Schuller, University of Tennessee - Knoxville
  • George Kabalka, University of Tennessee - Knoxville
  • G Smith
  • A Mereddy
  • M Akula
  • Maria Cekanova, MS, RNDr, PhD, University of Tennessee - Knoxville
Abstract

The enzyme cyclooxygenase-2 (COX-2) is overexpressed in many cancers, cardiovascular disease, neurodegenerative disorders, and arthritis. Selective inhibitors of COX-2 have been developed as therapeutics or preventive agents for these diseases. However, recent reports have revealed a significant increase in cardiovascular mortality in long-term users of the COX-2 inhibitors Vioxx and Celebrex, emphasizing the need for noninvasive tests that allow the identification of individuals whose COX-2 levels are overexpressed prior to assignment to treatment with these drugs. In this study, we have prepared a radioiodinated analogue of the selective COX-2 inhibitor celecoxib, and verified its binding to the COX-2 enzyme in vitro. Biodistribution studies in hamsters demonstrated significantly higher levels of radiotracer in animals treated with the tobacco carcinogen NNK in lung, pancreas, and liver. Assessment of COX-2 levels by whole-body planar nuclear imaging two hours after injection of the radiotracer was suggestive of a distinct increase in COX-2 in the pancreas and liver of a hamster treated for 10 weeks with NNK, in the lungs and liver of a second animal, and in the liver only, in two additional animals from the same treatment group. Immunostains showed selective overexpression of COX-2 in pre-neoplastic lesions of the pancreas and lungs in only those animals that showed tracer accumulation in these organs and in the livers of all NNK-treated hamsters. Immunostains for COX-1 yielded detectable reactions in the intestinal epithelium but not in pancreas, lungs, or liver, supporting the specificity of the tracer for COX-2. Our data provide proof of principle for the hypothesis that molecular imaging with radiolabeled COX-2 inhibitors can be used for the noninvasive monitoring of overexpressed COX-2 levels.

Publication Date
June, 2006
Citation Information
Hildegard Schuller, George Kabalka, G Smith, A Mereddy, et al.. "Detection of overexpressed COX-2 in precancerous lesions of hamster pancreas and lungs by molecular imaging: implications for early diagnosis and prevention" ChemMedChem Vol. 1 Iss. 6 (2006)
Available at: http://works.bepress.com/maria_cekanova/12/