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Preparation and animal studies of 99 TcmTRODAT1 as a dopamine transporter imaging agent

FANG Ping, WU Chunying, CHEN Zhengping, et al State Key Laboratory of Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063  
Objective To develop 99 Tcm labeled dopamine transporter (DAT) imaging agent 99 Tcm(2 N,N bis(2mercaptoethyl) ethylenediamino]methyl, 3(4chlorophenyl)tropane (TRODAT1) for evaluating changes of DAT in patients with Parkinson's disease Methods TRODAT1 was synthesized from cocaine by stepwise reactions adding two aminoethanethiol units Using SnCl2 as reducing agent, and in the presence of Naglucoheptonate, 99 TcmTRODAT1 was prepared Animal studies have been performed in rats and normal monkeys Results The structure of TRODAT1 was confirmed by IR, 1 HNMR and MS Radiochemical purity of 99 TcmTRODAT1 was over 90%, and stable for 24 h at room temperature The partition coefficient in octanol and buffer was 132 and 154 at pH 70 and 74 respectively Biodistribution displayed relatively low uptake in rat brain (028 and 012%ID/organ at 2 min and 60 min post injection, respectively), but high uptake in liver (167%ID/organ at 60 min), steady uptake in kidney (maintained 3%ID/organ) The major radioactivity was excreted by hepatobiliary systems The distribution in rat's brain showed that striatal uptake were 0193, 0189, 0142 and 0136%ID/g at 2, 30, 60 and 120 min, respectively The ratios of striatal to cerebellar, striatal to hippocampal and striatal to cortical were 445 255 and 315 at 120 min post injection, respectively Brain image studies in monkeys indicated that TRODAT was uptaked and retained in the basal ganglia, where containing DAT abundantly Ratio of regional brain uptakes of striatum/cerebellum was 156 as measured by SPECT imaging at 120 min Conclusions Above results showed the stable, neutral and lipophilic complex 99TcmTRODAT1 can cross the blood brain barrier, and be selectively concentrated by the striatal area, where containing DAT abundantly High quality images of monkeys were also obtained It suggested that 99 TcmTRODAT1 may be a promising agent for clinical application
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