^(99)Tc^m-小分子多肽配合物显像剂的合成及其在小鼠体内的生物分布研究  

SYNTHESIS OF LABELLED SMALL PEPTIDE COMPLEXES FOR IMAGING AGENTS WITH TECHNETIUM-99m AND BIODISTRIBUTION IN MICE

作　　者：齐传民[1] 郭雪峰[1] 张华北[1] 李波[1] 金未[1] 戴梅[1] 

机构地区：[1]北京师范大学化学系,北京100875

出　　处：《药学学报》2002年第7期522-526,共5页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金资助项目 ( 2 0 1710 0 8;2 980 10 0 2 )

摘　　要：目的　寻求新的心、肾显像剂。方法与结果　以巯基乙酸为初始原料 ,用不同的羧基活化的方法设计合成了 5个新的目标配体 ,其结构经光谱鉴定 (IR ,1 HNMR ,1 3 CNMR ,MS和元素分析 )。将合成的 5个新目标配体进行了锝 99m放射性标记 ,研究了其在小鼠体内的生物分布特征。结论　99Tcm MVG2 有较高的肾摄取 ,较长时间的肾滞留 ,血清除快 ,且肾与其他组织的活度比值高 ,具备成为肾功能显像剂的条件 ;99Tcm MVGT ,99Tcm MVGH和99Tcm MPGT均有较高的心肌初始摄取 ,但心肌滞留不好 ,血清除慢 ,心肌与其他组织的活度比值不高 ,主要从肝、肾中代谢。AIM To look for new heart or kidney imaging agents. Five new target chelators 2-N-(2′-s-triphenylmethylacetyl) amino-(N′-acetyl glycine) isovalericamide (MVG 2), 2-N-(2′-s-triphenylmethylacetyl) amino-[N′-acetyl-(N″-butylacetaminde)] isovalericamide (MVGT), 2-N-(2′-s-tri-phenylmethylacetyl) amino-[N′-acetyl-(N″-cyclohexanylacetaminde)] isovalericamide (MVGH), 2-N-(2′-s-triphenylmethylacetyl) amino-[N′-acetyl-(N″-butylacetaminde)] phenyl propamide (MPGT) and 2-N-(2′-s-triphenylmethylacetyl) amino-[N′-acetyl-(N″-cyclohexanylacetaminde)] phenylpropamide (MPGH) were synthesized as primitive materials to explore the synthetic methods of polypeptides. METHODS AND RESULTS All target chelators were identified on the basis of the spectroscopic data, such as IR, 1HNMR, 13 CNMR and elementary analysis. Different active esters with mercaptoacetic acid as primitive materials were used to explore the biodistribution of Technetium-99m labelling chelators in mice. The chelators were labeled with Technetium-99m and further tested for the biological activity in mice. Values given in ID which is the percentage injected dose per organ was tested to explore new heart imaging agents. The ID was determined in vivo by biodistribution study. Tc-99m complexes 0.1 mL was injected into laterial tail vein of 3 anaesthetised rats. At 2, 5, 10, 30, 60 minutes post-injection, rats were sacrificed by decapitation, bled from the neck and the organs were removed. The radioactivities in various organs were determined in an automatic twin crystal gamma counter. Five new target chelators were labeled with Technetium-99m in high yield ( >95% ). The bio-distribution resulted in mice indicate that 99 Tc m-MVG 2 has high kidney uptake, good retention, quick blood clearance and high activity ratios of kidneys to other tissues. 99 Tc m-MVGT, 99 Tc m-MVGH and 99 Tc m-MPGT have better heart accumulation, but shorter retention, slower blood clearance and lower activity ratios of kid

关 键 词：^99Tc^m-小分子多肽配合物显像剂 心、肾显像剂 锝-^99m放射性标记 生物分布 巯基乙酸 

分 类 号：R962[医药卫生—药理学]