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由于血-脑屏障(BBB)的存在,~(99m)Tc-EC和~(99m)Tc-MAMA’-BA等非脂溶性~(99m)Tc配合物不能进入动物脑组织中.利用血-脑屏障上富含特异性胰岛素受体蛋白这一特点,将水溶性~(99m)Tc-EC和~(99m)Tc-MAMA’-BA与胰岛素偶联后,经过分离,得到了两种新的~(99m)Tc标记偶联物:~(99m)Tc-EC-胰岛素和~(99m)Tc-MAMA’-BA-胰岛素,其放化纯度可达到90%以上,且具有较好的体外稳定性,期望它们的脑摄取比未偶联胰岛素的相应~(99m)Tc标记小分子配体能够有所提高,以从原理上证明:难以进脑的非脂溶性小分子~(99m)Tc标记配合物与胰岛素偶联后,可形成一种脑转运体,通过脑毛细血管内皮细胞膜上富含的特殊受体蛋白(如胰岛素受体蛋白)等,经过胞吞胞吐作用将~(99m)Tc标记物内化进脑.随后进行的小鼠体内生物分布实验结果表明,两种偶联物的确都较相应的小分子~(99m)Tc标记配合物脑摄取有所提高,脑摄取比值最高能够达到4~6倍(2~3h).这样将可开辟一条难以进脑的~(99m)Tc标记配合物穿过血-脑屏障进脑的新途径,对目前正在进行的~(99m)Tc标记神经受体显像剂药物克服BBB障碍,具有潜在的研究价值.
Due to the presence of blood-brain barrier (BBB), non-fat soluble 99m Tc complexes such as 99m Tc-EC and 99m Tc-MAMA’-BA can not enter the brain tissue of animals, The brain barrier is rich in specific insulin receptor protein. After the water-soluble ~ (99m) Tc-EC and ~ (99m) Tc-MAMA’-BA were coupled with insulin, ~ (99m) Tc-labeled conjugates: ~ (99m) Tc-EC-insulin and ~ (99m) Tc-MAMA’-BA-insulin, the radiochemical purity of more than 90%, and has better in vitro Stability, it is expected that their brain uptake can be increased relative to the corresponding ~ (99m) Tc-labeled small molecule ligands of unconjugated insulin to prove in principle that it is difficult to enter the non-fat soluble small molecule ~ (99m) Tc The labeled complex can be coupled with insulin to form a brain transporter through which the specific receptor protein (such as insulin receptor protein) is abundant on the membrane of brain capillary endothelial cells. After exocytosis, ~ (99m ) Tc markers were internalized into the brain.The subsequent biodistribution experiments in mice showed that the two conjugates did indeed show higher brain uptake than the corresponding small molecule ~ (99m) Tc-labeled complexes, and the brain uptake ratio most High to reach 4 to 6 times (2 ~ 3h) .This will open up a difficult brain into the (99m) Tc-labeled complex through the blood-brain barrier into the brain a new way, the ongoing ongoing ~ (99m ) Tc-labeled neural receptor imaging agents overcome BBB disorders, with potential research value.