摘要
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。
The 13I-FP-β-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) was prepared by ourselves. Its partition coefficients were determined. Kinetics of blood clearance in rabbits, biodistribution in rats brains, toxicity test in mice as well as autoradiography in rat's brain, SPECT imaging in normal monkey's brain were studied. The partition coefficients were 15 and 28 at pH 7.0 and 7.4 respectively. The brain uptake in rats was rapid (0.78, 0.59 %ID/organ at 2 min, 2 h after injection respectively), the ratios of striatum/cerebellum, striatum /frontal cortex and striatum / hippocampus were 5.2,2.2 and 3.1 at 1 h in rat's brain. The uptake in striatum could be blocked by p-CFT, suggesting that 131I-FP-β-ClT binds to DAT specifically. The compound was rapidly cleared from rabbits' blood, taking only 2 min to reduce to half of the original concentration. The ratio of striatum/occipital cortex is 2.7 in autoradiography of rat's brain. l31l-FP-β-CIT concentrated in striatum in SPECT imaging in normal monkey. The ratio of striatum /cerebellum and striatum /occipital cortex were 5.4 and 6.0 respectively at 2 h. The test of toxicity showed that the dose received by mice was 750 times by human, proving the agent was safe. These results suggest that the compound is a good SPECT imaging agent for DAT.
出处
《核技术》
CAS
CSCD
北大核心
2003年第11期858-862,共5页
Nuclear Techniques
基金
国家自然科学基金(39770230)
卫生部科研基金(98-1-326)
江苏省卫生厅重点科研基金(H2008)资助
