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Characterization of the Binding Sites for ¹²³I-ADAM and the Relationship to the Serotonin Transporter in Rat and Mouse Brains Using Quantitative Autoradiography

¹ Graduate Institute of Clinical Medical Sciences, Chang-Gung University, Tao-Yuan, Taiwan
² Department of Nuclear Medicine, Chang-Gung Memorial Hospital, Tao-Yuan, Taiwan
³ Division of Radiological Technology, School of Medical Technology, Chang-Gung University, Tao-Yuan, Taiwan
⁴ Department of Medical Radiation Technology and Institute of Radiological Sciences, National Yang-Ming University, Taipei, Taiwan
⁵ Institute of Nuclear Energy Research, Tao-Yuan, Taiwan
⁶ Department of Pharmacology, Chang-Gung University, Tao-Yuan, Taiwan

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.

Key Words: quantitative autoradiography • serotonin transporter • biodistribution