title: Synthesis and in vivo evaluation of [18F]-4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide as a PET imaging probe for COX-2 expression.
abstract: Synthesis of [18F]4-[5-(4-methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide ([18F]celecoxib), a selective COX-2 inhibitor, is achieved via a bromide to [18F]F- exchange reaction. Synthesis of the precursor for radiolabeling was achieved from 4'-methylacetophenone in four steps with 22% overall yield. Under non-radioactive conditions, fluorination was achieved using TBAF in DMSO at 135 degrees C in 80% yield. Synthesis of [18F]celecoxib was achieved using [18F]TBAF in DMSO at 135 degrees C in 10+/-2% yield (EOS) with >99% chemical and radiochemical purities. The specific activity was 120+/-40 mCi/micromol (EOB). [18F]celecoxib was found to be stable in ethanol, however, de[18F]fluorination (6.5%) was observed after 4 h in 10% ethanol-saline solution. Rodent PET studies show bone labeling indicating in vivo de[18F]fluorination of [18F]celecoxib. PET studies in baboon indicated a lower rate of de[18F]fluorination than rat and retention of radioactivity in brain regions consistent with the known distribution of COX-2. A radiolabeling method that can generate consistent high specific activity is needed for routine human use.
authors.affiliation: Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Jaya
authors.initials: J
authors.lastname: Prabhakaran
authors.forename: Mark D
authors.initials: MD
authors.lastname: Underwood
authors.forename: Ramin V
authors.initials: RV
authors.lastname: Parsey
authors.forename: Victoria
authors.initials: V
authors.lastname: Arango
authors.forename: Vattoly J
authors.initials: VJ
authors.lastname: Majo
authors.forename: Norman R
authors.initials: NR
authors.lastname: Simpson
authors.forename: Ronald
authors.initials: R
authors.lastname: Van Heertum
authors.forename: J John
authors.initials: JJ
authors.lastname: Mann
authors.forename: J S Dileep
authors.initials: JS
authors.lastname: Kumar
mesh_terms: D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging; D001921:Brain / Q000000981:diagnostic imaging; D051546:Cyclooxygenase 2 / Q000032:analysis* / Q000493:pharmacokinetics; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis* / Q000493:pharmacokinetics; D010215:Papio; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D012377:Rodentia; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution; D000096926:Benzenesulfonamides
chemical_list: D051546:Cyclooxygenase 2; D005462:Fluorine Radioisotopes; D008565:Membrane Proteins; D019275:Radiopharmaceuticals; D013449:Sulfonamides; D000096926:Benzenesulfonamides; C496540:PTGS2 protein, human