Validation of 4-[18F]-ADAM as a SERT imaging agent using micro-PET and autoradiography

• Published in: NeuroImage (Orlando, Fla.) Vol. 45; no. 3; pp. 687 - 693
• Main Authors: Ma, Kuo-Hsing, Huang, Wen-Sheng, Kuo, Yu-Yeh, Peng, Chi-Jiun, Liou, Nien-Hsien, Liu, Ren-Shyan, Hwang, Jeng-Jong, Liu, Jiang-Chuan, Chen, Haw-Jan, Shiue, Chyng-Yann
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.04.2009; Elsevier Limited
• Subjects: 4-[18F]-ADAM; 5,7-Dihydroxytryptamine; Animals; Autoradiography; Benzylamines - pharmacokinetics; Binding sites; Brain; Brain - diagnostic imaging; Brain research; Drug dosages; Ethanol; Fluorides; Male; Medical imaging; NMR; Nuclear magnetic resonance; p-Chloroamphetamine; Paroxetine; Positron emission tomography; Radiopharmaceuticals - pharmacokinetics; Rats; Rats, Sprague-Dawley; Rodents; Serotonin; Serotonin Plasma Membrane Transport Proteins - metabolism; Serotonin transporters; Studies; Tissue Distribution; Paroxetine; Autoradiography; 4-[18F]-ADAM; p-Chloroamphetamine; 5,7-Dihydroxytryptamine; Positron emission tomography; Serotonin transporters
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2008.12.060

Serotonin transporters (SERTs) have been implicated in various neuropsychiatric disorders. We aim to validate 4-[18F]-ADAM (N,N-dimethyl-2-(2-amino-4-[18F]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-[18F]-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-[18F]-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-[18F]-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-[18F]-ADAM binding when compared to normal controls. Rats pretreated with p-chloroamphetamine exhibited significant inhibition of 4-[18F]-ADAM uptake in brain regions rich in SERT over a period of four weeks. Thus, 4-[18F]-ADAM is a SERT-specific radioligand that may be useful for evaluating neuropsychiatric conditions involving serotonergic dysfunction.