Nuclear Science and Techniques

《核技术》(英文版) ISSN 1001-8042 CN 31-1559/TL     2019 Impact factor 1.556

Nuclear Science and Techniques ›› 2007, Vol. 18 ›› Issue (4): 218 doi: 10.1016/S1001-8042(07)60049-9


Biological evaluation on 125I-ADAM as serotonin transporter ligand

LEI Bei1,2 ZHU Junqing1 LU Chunxiong1 JIANG Quanfu1 ZOU Meifeng1 WANG Songpei1 LI Xiaomin1 WU Chunying1,2*   

  1. 1 The Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China;
    2 Huashan Hospital, Fudan University, Shanghai 200040, China
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LEI Bei ZHU Junqing LU Chunxiong JIANG Quanfu ZOU Meifeng WANG Songpei LI Xiaoming WU Chunying. Biological evaluation on 125I-ADAM as serotonin transporter ligand.Nuclear Science and Techniques, 2007, 18(4): 218     doi: 10.1016/S1001-8042(07)60049-9

Abstract: ADAM (2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine) is suggested as a promising serotonin transporter (SERT) imaging agent for central nervous system. In this paper, biodistribution studies in rats showed that the initial uptake of 131I-ADAM in the brain was high (1.087%ID at 2 min post-injection), and consistently displayed the highest binding (between 60~240 min post-injection) in hypothalamus, a region known with the highest density of SERT. The specific binding((T/CB)-1) of 131I-ADAM in hypothalamus were 2.94, 3.03 and 3.09 at 60, 120 and 240 min post-injection, respectively. The (T/CB)-1 was significantly blocked by pretreatment with paroxetine, which is known as a serotonin site reuptake inhibitor, while another nonselective competing drug (5HT2A antagonist) Ketanserin, showed no block effect. The rat brain autoradiography and analysis showed that there was a high 131I-ADAM uptake in hypothalamus, the ratio of hypothalamus/cerebellum was significantly reduced from 7.94±0.39 to 1.30±0.56 by pretreatment with paroxetine at 60 min post-injection. Blood clearance kinetics was performed in rats, and the initial half-life of 13.79 min and late half-life of 357.14 min were obtained. The kinetic equation is: C=3.6147e-0.0725t + 1.0413e-0.0028t. The thyroid uptake was 0.009% ID and 1.421% ID at 2 min and 120 min post-injection, respectively, suggesting that in vivo deiodination may be the major route of metabolism. Toxicity trial showed that the dose per kilogram administered to mice was 1000 times greater than that to humans, assuming a weight of 50kg. These data suggest that 131I-ADAM may be useful for SPECT imaging of SERT binding sites in the brain.

Key words: Depression, SERT, ADAM, Imaging agent, Radionuclide imaging, Biodistribution