Aβ斑块显像剂^(11)C-苯并呋喃衍生物的研究  

^(11)C labelled benzofuran derivatives as a new agent for β-amyloid imaging

作　　者：张锦明[1] 郭喆[1] 田嘉禾[1] 王武尚[2] 刘伯里[3] 

机构地区：[1]解放军总医院核医学科,北京100853 [2]西安西北核技术研究院 [3]北京师范大学化学系

出　　处：《中华核医学杂志》2007年第1期38-40,共3页Chinese Journal of Nuclear Medicine

基　　金：国家自然科学基金(20471011)

摘　　要：目的合成新的^(11)C 标记小分子苯并呋喃衍生物并研究其生物学性质。方法合成前体5-溴2-(4-胺基苯)苯并呋喃,用改良的^(11)CH_3I 法标记,生成5-溴-2-(4-N-^(11)C-甲胺基苯)-苯并呋喃,以柱色层法测标记率。正常小鼠尾静脉注射5-溴-2-(4-N-^(11)C-甲胺基苯)-苯并呋喃后不同时间处死,测每克组织百分注射剂量率(%ID/g)。结果改良^(11)CH_3I 法标记率为45%,放化纯大于95%。小鼠尾静脉注射药物后,放射性主要分布于肝和肾内,药物能迅速被脑摄取,2 min 达到3.2%ID/g,正常脑对其清除快于对碘的取代物,2与30 min 放射性摄取比值为1.34。结论 ^(11)C 标记小分子溴取代苯并呋喃衍生物,可作为β-淀粉样蛋白(Aβ)显像剂,其生物学性质明显优于碘的取代物。Objective Deposit of β-amyloid protein （Aβ） as senile plaque is one of the pathophysiologic features in Alzheimer＇s disease. Several new derivatives of benzofuran were synthesized, ^11C labelled, and tested as the potential imaging agents for targeting amyloid deposit. Methods 5-Br-2-（4-aminophenyl） benzofuran was synthesized and labelled by an improved method, in which the precursors were mixed with ^11 CH31 and dimethyl sulfoxide （DMSO） solution to get 5-Br-2-（4-N-^11C-methylaminophenyl） benzofuran. The column method was employed to measure the labelling yields. The biodistribution of the product was studied in 9 normal mice. The characters of the precursor were confirmed by l H NMR. Results The labelling yield was 45% with the author＇s improved method used in the current study. The radiochemical yield was over 95%. Most of the radioactivity was observed in liver and kidney after intravenous injection. The peak uptake in normal mice brain （3.2 % ID/g） was noted at 2 min post-injection with a washout faster for 5-Br-substituent than 5-I-substituent. The 2/30 min ratio of cerebral uptake was 1.34. Conclusion The new derivative, ^11C labelled 5-Br-substituent, showed certain characteristics more favorable than literature reported 5-I-substituent as an Aβ imaging agent.

关 键 词：苯呋喃类 碳放射性同位素 化学合成 淀粉样Β蛋白 放射性核素显像 小鼠 药代动力学 

分 类 号：R817[医药卫生—影像医学与核医学]