101. Characterization of 4-[18F]-ADAM as an imaging agent for SERT in non-human primate brain using PET: a dynamic study
- Author
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Shyh-Jen Wang, Cheng Yu Chen, Wen-Sheng Huang, Cheng-Yi Cheng, Ren-Shyan Liu, Yu-An Chen, San Yuan Huang, I-Hsun Li, Chyng-Yann Shiue, Kuo-Hsing Ma, and Yaoh-Shiang Lin
- Subjects
Male ,Cancer Research ,Biodistribution ,medicine.medical_specialty ,Benzylamines ,Fluorine Radioisotopes ,N-Methyl-3,4-methylenedioxyamphetamine ,Thalamus ,Striatum ,Sensitivity and Specificity ,Serotonin Agents ,Internal medicine ,Fluoxetine ,medicine ,Radioligand ,Animals ,Radiology, Nuclear Medicine and imaging ,Tissue Distribution ,Serotonin transporter ,Serotonin Plasma Membrane Transport Proteins ,biology ,medicine.diagnostic_test ,business.industry ,Chemistry ,Brain ,Reproducibility of Results ,MDMA ,Imaging agent ,Endocrinology ,Positron emission tomography ,Positron-Emission Tomography ,biology.protein ,Molecular Medicine ,Macaca ,Female ,Nuclear medicine ,business ,Selective Serotonin Reuptake Inhibitors ,medicine.drug - Abstract
Introduction Serotonin transporter (SERT) has been associated with many psychiatric diseases. This study investigated the biodistribution of a serotonin transporter imaging agent, N,N -dimethyl-2-(2-amino-4- 18 F-fluorophenylthio)benzylamine (4-[ 18 F]-ADAM), in nonhuman primate brain using positron emission tomography (PET). Methods Six and four Macaca cyclopis monkeys were used to determine the transit time (i.e., time necessary to reach biodistribution equilibrium) and the reproducibility of 4-[ 18 F]-ADAM biodistribution in the brain, respectively. The sensitivity and specificity of 4-[ 18 F]-ADAM binding to SERT were evaluated in one monkey challenged with different doses of fluoxetine and one monkey treated with 3,4-methylendioxymethamphetamine (MDMA). Dynamic PET imaging was performed for 3 h after 4-[ 18 F]-ADAM intravenous bolus injection. The specific uptake ratios (SURs) in the midbrain (MB), thalamus (TH), striatum (ST) and frontal cortex (FC) were calculated. Results The distribution of 4-[ 18 F]-ADAM reached equilibrium 120–150 min after injection. The mean SURs were 2.49±0.13 in MB, 1.59±0.17 in TH, 1.35±0.06 in ST and 0.34±0.03 in FC, and the minimum variability was shown 120–150 min after 4-[ 18 F]-ADAM injection. Using SURs and intraclass coefficient of correlation, the test/retest variability was under 8% and above 0.8, respectively, in SERT-rich areas. Challenge with fluoxetin (0.75–2 mg) dose-dependently inhibited the SURs in various brain regions. 4-[ 18 F]-ADAM binding was markedly reduced in the brain of an MDMA-treated monkey compared to that in brains of normal controls. Conclusion 4-[ 18 F]-ADAM appears to be a highly selective radioligand for imaging SERT in monkey brain.
- Published
- 2011