title: Validation of 4-[18F]-ADAM as a SERT imaging agent using micro-PET and autoradiography.
abstract: Serotonin transporters (SERTs) have been implicated in various neuropsychiatric disorders. We aim to validate 4-[(18)F]-ADAM (N,N-dimethyl-2-(2-amino-4-[(18)F]fluorophenylthio)benzylamine) as a SERT imaging agent in rats using micro-positron emission tomography (micro-PET) and autoradiography. Sixty to ninety min after injecting 4-[(18)F]-ADAM, specific uptake ratios (SURs) were determined by micro-PET measurements in various brain regions of normal control rats. For n=3, the SUR in the midbrain was 4.94+/-0.16, for the hypothalamus it was 4.39+/-0.031 and for the caudate it was 4.18+/-0.53. The retention of 4-[(18)F]-ADAM in the hypothalamus and midbrain regions increased rapidly between 5 to 10 min after injection and declined thereafter. The SURs determined by autoradiography were: 9.31+/-1.41 for the midbrain, 7.15+/-1.45 for the hypothalamus and 5.22+/-1.14 for the caudate putamen. Both micro-PET and autoradiography studies revealed a dose-dependent progressive inhibition of radioligand uptake in the frontal cortex, caudate putamen and hypothalamus in rats treated with 0.01 to 0.25 mg/kg paroxetine. A decrease in 4-[(18)F]-ADAM uptake of approximately 84% was observed in the midbrain of rats pretreated with 0.25 mg/kg paroxetine as compared to controls (4.94+/-0.16 versus 0.80+/-0.17, n=3). Both 5,7-dihydroxytryptamine and p-chloroamphetamine-treated rats showed pronounced reduction in 4-[(18)F]-ADAM binding when compared to normal controls. Rats pretreated with p-chloroamphetamine exhibited significant inhibition of 4-[(18)F]-ADAM uptake in brain regions rich in SERT over a period of four weeks. Thus, 4-[(18)F]-ADAM is a SERT-specific radioligand that may be useful for evaluating neuropsychiatric conditions involving serotonergic dysfunction.
authors.affiliation: Department of Biology and Anatomy, National Defense Medical Center, Taipei, Taiwan. kuohsing91@yahoo.com.tw
authors.forename: Kuo-Hsing
authors.initials: KH
authors.lastname: Ma
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Huang
authors.forename: Yu-Yeh
authors.initials: YY
authors.lastname: Kuo
authors.forename: Chi-Jiun
authors.initials: CJ
authors.lastname: Peng
authors.forename: Nien-Hsien
authors.initials: NH
authors.lastname: Liou
authors.forename: Ren-Shyan
authors.initials: RS
authors.lastname: Liu
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
authors.forename: Jiang-Chuan
authors.initials: JC
authors.lastname: Liu
authors.forename: Haw-Jan
authors.initials: HJ
authors.lastname: Chen
authors.forename: Chyng-Yann
authors.initials: CY
authors.lastname: Shiue
mesh_terms: D000818:Animals; D001345:Autoradiography; D001596:Benzylamines / Q000493:pharmacokinetics*; D001921:Brain / Q000000981:diagnostic imaging*; D008297:Male; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050486:Serotonin Plasma Membrane Transport Proteins / Q000378:metabolism*; D014018:Tissue Distribution
chemical_list: D001596:Benzylamines; C475911:N,N-dimethyl-2-(2-amino-4-fluorophenylthio)benzylamine; D019275:Radiopharmaceuticals; D050486:Serotonin Plasma Membrane Transport Proteins