title: Synthesis and evaluation in vitro and in vivo of a 11C-labeled cyclooxygenase-2 (COX-2) inhibitor.
abstract: The radiosynthesis and radiopharmacological evaluation of 1-[(11)C]methoxy-4-(2-(4-(methanesulfonyl)phenyl)cyclopent-1-enyl)-benzene [(11)C]5 as novel PET radiotracer for imaging of COX-2 expression is described. The radiotracer was prepared via O-methylation reaction with [(11)C]methyl iodide in 19% decay-corrected radiochemical yield at a specific activity of 20-25GBq/mumol at the end-of-synthesis within 35 min. The radiotracer [(11)C]5 was evaluated in vitro using various pro-inflammatory and tumor cell lines showing high functional expression of COX-2 at baseline or after induction. In vivo biodistribution of compound [(11)C]5 was characterized in male Wistar rats. Compound [(11)C]5 was rapidly metabolized in rat plasma, and more pronounced, in mouse plasma. In vivo kinetics and tumor uptake were demonstrated by dynamic small animal PET studies in a mouse tumor xenograft model. Tumor uptake of radioactivity was clearly visible overtime. However, radioactivity uptake in the tumor could not be blocked by the pre-injection of nonradioactive compound 5. Therefore, it can be concluded that radioactivity uptake in the tumor was not COX-2 mediated.
authors.affiliation: Institute of Radiopharmacy, Research Center Dresden-Rossendorf, PO Box 510119, 01314 Dresden, Germany. f.wuest@fz-rossendorf.de
authors.forename: Frank
authors.initials: F
authors.lastname: Wuest
authors.forename: Torsten
authors.initials: T
authors.lastname: Kniess
authors.forename: Ralf
authors.initials: R
authors.lastname: Bergmann
authors.forename: Jens
authors.initials: J
authors.lastname: Pietzsch
mesh_terms: D000818:Animals; D002250:Carbon Radioisotopes; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000201:enzymology / Q000378:metabolism; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D014018:Tissue Distribution
chemical_list: D002250:Carbon Radioisotopes; D052246:Cyclooxygenase 2 Inhibitors; D003517:Cyclopentanes; D019275:Radiopharmaceuticals; D051546:Cyclooxygenase 2