多巴胺D2受体显像剂^(125)I-DMAIBZM的合成及生物分布实验

Synthesis and Biodistribution of ^(125)I-DMAIBZM for Dopamine D2 Receptor Imaging

许多中枢神经系统的疾病如帕金森病等,与脑内多巴胺神经递质异常有关.利用放射性脑受体显像技术可以了解多巴胺受体信息,进而获得多巴胺的信息变化.苯甲酰胺类衍生物125I-(S)-N-(1-乙基-2-吡咯烷基)甲基-4-氨基-2-甲氧基苯酰胺(125I-AIBZM)与多巴胺D2受体具有很高的亲和力,但其入脑量很低.为提高125I-AIBZM的入脑量,本文对其标记前体(S)-N-(1-乙基-2-吡咯烷基)甲基-4-氨基-2-甲氧基苯酰胺(ABZM)的结构进行改造,得到了新的化合物(S)-4-二甲氨基-N-(1-乙基-2-吡咯烷基)甲基-2-甲氧基苯酰胺(DMABZM).通过Idogen法对DMABZM进行标记得到标记化合物125I-DMAIBZM,标记率为74%,放化纯度达到99%.125I-DMAIBZM的脂溶性显著大于125I-AIBZM,入脑量有较大的提高.体外放射配基结合实验测得DMABZM的IC50为2.9589×10-7mol/L,表明其与多巴胺D2受体特异性结合且具有较高的亲和力,小鼠体内的分布实验表明,该标记物纹状体/小脑的放射性计数比可达6.5左右,说明该标记化合物可特异性介导到纹状体.本文结果表明,125I(123I)-DMAIBZM有望用于多巴胺D2受体的显像.

Many kinds of central nervous system diseases,such as Parkinson＇s disease,have great relationship with abnormality of cerebral dopaminergic neurotransmission.Radioactive brain receptor imaging technique can be used to acquire the information of dopamine receptor to infer the situation of dopamine.（S）-5-125I-N-（1-Ethyl-2-pyrrolidinyl）methyl-4-amine-2-methoxy-benzamide（125I-AIBZM） shows high binding affinity with dopaminergic receptor;however,the application of 125I-AIBZM is limited for its low brain biodistribution.To improve the brain uptake of the compound 125I-AIBZM,the structure modification was performed on its labeled precursors（S）-5-N-（1-ethyl-2-pyrrolidinyl）methyl-4-amine-2-methoxy-benzamide（ABZM）,resulting in a new compound 125I-DMAIBZM[（S）-5-125I-iodo-N-（1-ethyl-2-pyrrolidinyl）methyl-4-dimethyl-amine-2-methoxy-benzamide].Labeling of DMABZM was achieved by Iodogen method with a radiochemical yield of 74%.After HPLC purification,radiochemical purity was more than 99%.The hydrophobicity of 125I-DMAIBZM was significantly higher than that of 125I-AIBZM.DMABZM had shown high binding affinity（IC50=2.9589×10-7 mol/L） with dopamine D2 receptor in rat brain.The brain biodistribution data for 125I-DMAIBZM（the ratio of 125I-DMAIBZM between striatum and cerebellum6.5） indicated its high specifi-city and affinity in striatum.The results show that 125I（123I）-DMAIBZM had much potential for dopamine D2 receptor imaging.