UNLABELLED: Cyclooxygenase-2 (COX-2) overexpression has been observed in various pathologies, such as inflammation, cancer, ischemia, and Alzheimer's disease. As an initial step toward a noninvasive PET technique to assay COX-2 expression, this study describes the synthesis and preliminary evaluation of the radiolabeled COX-2 inhibitor (18)F-desbromo-DuP-697. METHODS: Desbromo-DuP-697 was radiolabeled by a nucleophilic aromatic substitution reaction of the nitro precursor with (18)F-fluoride. Biodistribution studies of the tracer were performed in a carrageenan-induced hyperalgesia rat model. Brain uptake was investigated with autoradiography. To confirm the results of the biodistribution, COX activity was determined by a peroxidase assay. RESULTS: Biodistribution studies showed specific binding of the tracer to COX-2 in heart, kidney, brain, and blood cells, but not in the inflamed paw, which was probably due to low COX-2 expression. In the brain, regional differences in tracer uptake were observed, with high uptake in cortical regions. (18)F-Desbromo-DuP-697 did not show any binding to COX-1. Nonspecific uptake was high in fat and intestines. CONCLUSION: Because of its ability to cross the blood-brain barrier, (18)F-desbromo-DuP-697 appears to be suitable for COX-2 imaging in the brain. Its high nonspecific uptake in the intestines may limit its use for imaging in the abdominal region.
UNLABELLED: Cyclooxygenase-2 (COX-2) overexpression has been observed in various pathologies, such as inflammation, cancer, ischemia, and Alzheimer's disease. As an initial step toward a noninvasive PET technique to assay COX-2 expression, this study describes the synthesis and preliminary evaluation of the radiolabeled COX-2 inhibitor (18)F-desbromo-DuP-697. METHODS:Desbromo-DuP-697 was radiolabeled by a nucleophilic aromatic substitution reaction of the nitro precursor with (18)F-fluoride. Biodistribution studies of the tracer were performed in a carrageenan-induced hyperalgesiarat model. Brain uptake was investigated with autoradiography. To confirm the results of the biodistribution, COX activity was determined by a peroxidase assay. RESULTS: Biodistribution studies showed specific binding of the tracer to COX-2 in heart, kidney, brain, and blood cells, but not in the inflamed paw, which was probably due to low COX-2 expression. In the brain, regional differences in tracer uptake were observed, with high uptake in cortical regions. (18)F-Desbromo-DuP-697 did not show any binding to COX-1. Nonspecific uptake was high in fat and intestines. CONCLUSION: Because of its ability to cross the blood-brain barrier, (18)F-desbromo-DuP-697 appears to be suitable for COX-2 imaging in the brain. Its high nonspecific uptake in the intestines may limit its use for imaging in the abdominal region.
Authors: Md Jashim Uddin; Brenda C Crews; Anna L Blobaum; Philip J Kingsley; D Lee Gorden; J Oliver McIntyre; Lynn M Matrisian; Kotha Subbaramaiah; Andrew J Dannenberg; David W Piston; Lawrence J Marnett Journal: Cancer Res Date: 2010-05-01 Impact factor: 12.701
Authors: Anuj K Yadav; Christopher J Reinhardt; Andres S Arango; Hannah C Huff; Liang Dong; Michael G Malkowski; Aditi Das; Emad Tajkhorshid; Jefferson Chan Journal: Angew Chem Int Ed Engl Date: 2020-02-06 Impact factor: 15.336
Authors: Daniele de Paula Faria; Sjef Copray; Carlos Buchpiguel; Rudi Dierckx; Erik de Vries Journal: J Neuroimmune Pharmacol Date: 2014-05-09 Impact factor: 4.147
Authors: Md Jashim Uddin; Brenda C Crews; Kebreab Ghebreselasie; Imran Huda; Philip J Kingsley; Mohammad Sib Ansari; Mohammed N Tantawy; Jeffery Reese; Lawrence J Marnett Journal: Cancer Prev Res (Phila) Date: 2011-09-07
Authors: Robin Goland; Matthew Freeby; Ramin Parsey; Yoshifumi Saisho; Dileep Kumar; Norman Simpson; Joy Hirsch; Martin Prince; Antonella Maffei; J John Mann; Peter C Butler; Ronald Van Heertum; Rudolph L Leibel; Masanori Ichise; Paul E Harris Journal: J Nucl Med Date: 2009-02-17 Impact factor: 10.057
Authors: Jun Yang; Donald A Bruun; Chang Wang; Debin Wan; Cindy B McReynolds; Kenny Phu; Bora Inceoglu; Pamela J Lein; Bruce D Hammock Journal: Toxicol Appl Pharmacol Date: 2019-09-12 Impact factor: 4.219
Authors: Md Jashim Uddin; Brenda C Crews; Kebreab Ghebreselasie; Mohammed N Tantawy; Lawrence J Marnett Journal: ACS Med Chem Lett Date: 2010-11-12 Impact factor: 4.345