TY - JOUR T1 - Characterization of the Binding Sites for <sup>123</sup>I-ADAM and the Relationship to the Serotonin Transporter in Rat and Mouse Brains Using Quantitative Autoradiography JF - Journal of Nuclear Medicine JO - J Nucl Med SP - 673 LP - 681 VL - 45 IS - 4 AU - Kun-Ju Lin AU - Tzu-Chen Yen AU - Shiaw-Pyng Wey AU - Jeng-Jong Hwang AU - Xin-Xian Ye AU - Kai-Yuan Tzen AU - Ying-Kai Fu AU - Jin-Chung Chen Y1 - 2004/04/01 UR - http://jnm.snmjournals.org/content/45/4/673.abstract N2 - Imaging of serotonin transporter (SERT) in the central nervous system may provide an important tool to evaluate some psychiatric disorders. Recently, a novel 123I-labeled radiotracer, 2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine (123I-ADAM), has been developed that exhibited a high selectivity for SERT. The aim of this study was to characterize the biodistribution and specificity of 123I-ADAM to SERT using quantitative autoradiography in both control and neurotoxin-treated animals. Methods: 123I-ADAM (74 MBq) was injected intravenously into the mice to access its biodistribution in the brain via quantitative autoradiography. Further, rats with serotonin depleted by intraperitoneal injection of p-chloroamphetamine (PCA) were used to evaluate the specificity of 123I-ADAM to SERT. The levels of biogenic amines were then measured and correlated with quantitative 123I-ADAM labeling in control and PCA-treated rat brains. Results: The autoradiographic results showed that 123I-ADAM accumulated in SERT-rich brain areas after systemic injection, including the globus pallidus, thalamus, hypothalamus, substantia nigra, interpeduncular nucleus, amygdala, and raphe nucleus. The dorsal raphe nucleus had the highest initial uptake with a peak specific binding ratio (i.e., [target − cerebellum]/cerebellum) at 120 min after injection. 123I-ADAM uptake was dramatically decreased in the hippocampus, thalamus, amygdala, geniculate nuclei, hypothalamus, raphe nucleus, and substantia nigra in PCA-lesioned rats. The decrement in radioactivity was more prominent at higher dosages of PCA and was in parallel with the changes in amounts of serotonin and 5-hydroxyindoleacetic acid in the prefrontal cortex. Conclusion: This study demonstrates that regional distribution of 123I-ADAM radioactivity is similar to the SERT localization in both rat and mouse brains. We also validated that destruction on central serotonergic neurons after PCA treatment inhibits the uptake of 123I-ADAM in serotonin-rich brain regions. High specific binding to SERT in vivo makes 123I-ADAM an appropriate radiotracer for solitary studies of serotonin functions in living humans. ER -