The preclinical pharmacological study of dopamine transporter imaging agent ¹⁸F-FP-β-CIT

The preclinical pharmacological study of dopamine transporter imaging agent 18 F-FP-β-CIT 1 first-author 1 corresp Correspondence author. E-mail: czp72@163.com Correspondence author. E-mail: czp72@163.com czp72@163.com 1 1 2 2 1 Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health , Wuxi 214063, China; Jiangsu Institute of Nuclear Medicine, Key Laboratory of Nuclear Medicine, Ministry of Health , Wuxi 214063, China; PET Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China PET Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, China The paper is to study pharmacologic characteristics of 18 F-FP-β-CIT ( 18 F-N-(3-fluoropropyl)-2β- carbomethoxy-3β- (4-iodophenyl)nortropane) as an imaging agent for dopamine transporter. The radiochemical purity of 18 F-FP-β-CIT in aqueous solution was over 95% after standing at room temperature for 4h. Biodistribution displayed rapid uptake in rat brain (1.375 %ID/organ at 5min and 0.100 %ID/organ at 180 min) and the striatal uptake was 1.444, 0.731, 0.397, 0.230 and 0.146 %ID/g at 5, 30, 60, 120 and 180 min, respectively. The values of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus in rat's brain at 30 min were 3.38, 2.17 and 2.40 respectively. The uptake in striatum can be blocked by β-CFT, suggesting that 18 F-FP-β-CIT binds to DAT peculiarly. The compound was rapidly cleared from monkey's blood. The striatal uptake was bilaterally decreased in the left-sided lesioned PD rats, compared with normal control. Brain PET imaging studies in normal monkey showed that 18 F-FP-β-CIT was concentrated in striatum. The test of undue toxicity showed that the dose received by mice was 1250 times as by human, which indicates that 18 F-FP-β-CIT is very safe. So 18 F-FP-β-CIT is a promising PET imaging agent for DAT with safety and validity. Parkinson's disease Dopamine transporter Radionuclide imaging 18 F-FP-β-CIT Biodistribution Pharmacokinetics References Abi-Dargham A , Gandelsman M S , De Erausquin G A , et al . J Nucl Med , 1996 , 37 : 1129 - 1133 . J Nucl Med Goodman M M , Keil R , Shoup T M , et al . J Nucl Med , 1997 , 38 : 119 - 126 . J Nucl Med Yung B C K , Dannals R F , Kuhar M J , et al . J Nucl Med , 1993 , 34 : S197 . J Nucl Med Kung H F , Kim H J , Kung M P , et al . Eur J Nucl Med , 1996 , 23 : 1527 - 1530 . Eur J Nucl Med Chalyl T , Dhawan V , Kazumata K , et al . Nucl Med Biol , 1996 , 23 : 999 - 1004 . Nucl Med Biol Fang Ping , Chen Zhengping , Lin Yansong , et al . Isotopes (in Chinese) , 2001 , 14 : 6 - 10 . Isotopes (in Chinese) Chen Zhengping , Wu Chunying , Zhang Zhengwei , et al . Chin J Nucl Med (in Chinese) , 2003 , 23 : 241 - 243 . Chin J Nucl Med (in Chinese) 10.1016/S1001-8042(07)60050-5 O628.5 + 1,R962,R742.5,R817 Supported by the National Natural Science Foundation of China (30570518) and Science Foundation of Health Department of Jiangsu Province (H200401) 2006-08-17 2007-08-20 2021-01-19 2007 Nuclear Science and Techniques 04 18