title: Preclinical studies on [11C]TMSX for mapping adenosine A2A receptors by positron emission tomography.
abstract: In previous in vivo studies with mice, rats and monkeys, we have demonstrated that [11C]TMSX ([7-methyl-11C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine) is a potential radioligand for mapping adenosine A2A receptors of the brain by positron emission tomography (PET). In the present study, we performed a preclinical study. A suitable preparation method for [11C]TMSX injection was established. The radiation absorbed-dose by [11C]TMSX in humans estimated from the tissue distribution in mice was low enough for clinical use, and the acute toxicity and mutagenicity of TMSX were not found. The striatal uptake of [11C]TMSX in mice was reduced by pretreatment with theophylline at the dose of 10 and 100 mg/kg, suggesting that the [11C]TMSX PET should be carefully performed in the patients received with theophylline. We have concluded that [11C]TMSX is suitable for mapping adenosine A2A receptors in the human brain by PET.
authors.affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan. ishiwata@pet.tmig.or.jp
authors.forename: Kiichi
authors.initials: K
authors.lastname: Ishiwata
authors.forename: Wei-Fang
authors.initials: WF
authors.lastname: Wang
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kawamura
authors.forename: Kenji
authors.initials: K
authors.lastname: Ishii
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D004355:Drug Stability; D006801:Humans; D008657:Metabolic Clearance Rate; D051379:Mice; D009152:Mutagenicity Tests; D009928:Organ Specificity; D011829:Radiation Dosage; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D043705:Receptor, Adenosine A2A / Q000378:metabolism*; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed / Q000379:methods*; D023382:Toxicity Tests, Acute; D014915:Whole-Body Counting; D014970:Xanthines / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity
chemical_list: C405422:KF18446; D019275:Radiopharmaceuticals; D043705:Receptor, Adenosine A2A; D014970:Xanthines