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报道了用自制的131I-FP-β-CIT(N-(3’-氟丙基)-2β-羰甲氧基-3β-(4’-碘苯基)托烷)测定分配比,进行大鼠体内及脑内分布、兔血药清除动力学、大鼠脑放射自显影、猴显像和异常毒性等实验。结果显示:131I-FP-β-CIT脂溶性大,在pH为7.0和7.4时的分配比分别为15和28;药物能迅速进脑,并有较好的滞留(2 min时脑摄取为0.78％ID,2 h时为0.59％ID);脑内药物在纹状体中浓聚,1h时纹状体与小脑、额叶、海马的比值分别为5.23、2.15和3.10;纹状体的摄取能被β-CFT阻滞,表明药物与多巴胺转运蛋白(DAT)结合的亲和性和特异性较好;药物在兔血中清除迅速,血药浓度降至一半所需时间约为2 min;放射自显影显示出药物在纹状体区域的放射性浓聚,左右纹状体基本对称,纹状体与顶叶的比值为2.7;正常猴显像表明在注药后2 h时纹状体与颞叶、小脑的比值分别为5.4和3.0;异常毒性实验结果显示小鼠所耐受的剂量为人的750倍,表明药物非常安全。以上结果表明131I-FP-β-CIT与DAT有很好的亲和性与特异性,其体内性质适合显像,具有良好的临床应用前景。
Reported that the distribution ratio was measured with a home-made 131I-FP-β-CIT (N- (3’-fluoropropyl) -2β-carbomethoxy-3β- (4’-iodophenyl) tropane) Rat and brain distribution, rabbit plasma clearance kinetics, brain autoradiography, monkey imaging and abnormal toxicity experiments. The results showed that 131I-FP-β-CIT was fat-soluble and had a distribution ratio of 15 and 28 at pH 7.0 and 7.4, respectively. The drug could rapidly enter the brain with better retention (brain uptake at 2 min was 0.78 % ID, 0.59% ID at 2 h). The intracerebral drug concentration in the striatum, the ratios of striatum to the cerebellum, frontal lobe and hippocampus at 1 hour were 5.23, 2.15 and 3.10, respectively. The uptake of striatum Can be blocked by β-CFT, indicating that the drug has good affinity and specificity for binding to dopamine transporter (DAT); the drug is rapidly cleared in rabbit blood and the time required for reducing blood concentration to half is about 2 min; Autoradiogram showed the radioactive concentration of the drug in the striatum region, the symmetry of the left and right striatum, striatum and parietal ratio was 2.7; normal monkey imaging showed striatum at 2 h after injection Temporal lobe and cerebellum were 5.4 and 3.0, respectively. Abnormal toxicity test results showed that the tolerated dose in mice was 750 times that of human, indicating that the drug was very safe. The above results show that 131I-FP-β-CIT and DAT have good affinity and specificity, and its in vivo properties suitable for imaging, has good clinical application prospects.