To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in t...To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article. The radio-chemical purity (RCP) of the labeled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1 .9%ID/organ in rats and 4.5%ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4 h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabo lized in liver because the hepatic uptake was much higher than other organs (75.4%ID/organ at 18h). The half-life of blood elimination was 5min The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that fl-CIT can be used as a potential DAT imaging agent.展开更多
基金Supported by the National Natural Science Foundation of China (39770230), Science Foundation of Health Ministry (98-1-326) and H
文摘To prepare 125/131I-β-CIT (2β-carbomethoxy-β- (4-iodophenyl)tropane) as an imaging agent for dopamine transporter (DAT), the labeling method from tributylstannyl precursor with peracetic acid has been reported in this article. The radio-chemical purity (RCP) of the labeled compound was over 95% determined by HPLC and TLC. The stability, partition coefficients were also determined. The pharmacological studies of the imaging agent were performed in rats, mice, rabbits and normal monkey. The ligand showed preferable uptake in brain (1 .9%ID/organ in rats and 4.5%ID/organ in mice at 5 min). The ratios of striatum/cerebellum, hippocampus/cerebellum and cortex/cerebellum were 28.9, 3.97 and 4.75 at 6 h in rats, and 8.52, 2.99 and 3.06 at 6h in mice, respectively. In monkey brain imaging the ratios of striatum/frontal cortex (ST/FC) and striatum/occipital cortex (ST/OC) were 5.14 and 5.97 at 4 h, respectively. All of above showed the high affinity of the ligand to DAT. The compound was primarily metabo lized in liver because the hepatic uptake was much higher than other organs (75.4%ID/organ at 18h). The half-life of blood elimination was 5min The dose received by mice was 2500 times as high as that received by human in the test of undue toxicity, which evaluated the safety of the agent. All the results suggest that fl-CIT can be used as a potential DAT imaging agent.
