Development of Porphyrin chelate for NMR imaging diagnosis agent

核磁共振成像诊断剂卟啉螯合物的研制

基本信息

批准号：
05555225
负责人：
IGARASHI Shukuro
金额：
$ 3.78万
依托单位：
Ibaraki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Developmental Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-05555225/
关键词：
Porphrin chelate NMR imaging Imaging diagnosis agent Arteriosclerosis Atheroma model support

项目摘要

It is known that some porphyrin compounds can be adsorbed on a cancerous tumor or a fat depot. The biomedical applications of them are expected as a reagent for PDT(photo dynamic therapy), X-ray CT and MRI (NMR imaging). In this work, three types of water-soluble porphyrins were synthesized for developing a new MRI angiographic agent which can accumulate into atheromas.Eight kinds of sulfonated porphyrin derivatives were synthesized by introducing a hydrophobic group such as an alkyl, a phenyl or a fluoring group for controlling a hydrophilic/hydrophobic balance. An Mn-tsbp molecule, which is a manganese complex of a sulfonated porphyrin derivative with four sulfobiphenyl groups, can be well absorbed on deoxy colic acid (DCA) as an early atheroma model and accumulated onto an atheroma 2-5 times greater than onto a normal aortic wall in the experiment using a rabbit. And good correlation coefficient (>0.8) was obtained with the experiments in vitro and in vivo.Five kind of aminoacid-porphyrin derivatives were synthesized. But the all products were tended to hydrolysis in aqueous solution. Three kinds of phosphorylated porphyrin derivatives were synthesized taking account of safety in vivo and their adsorption selectivity on the calcification of an atheroma. An Mn-tpppd molecule, which is a manganese complex of a phosphorylated porphyrin derivative with eight phosphonooxy groups, can be well absorbed on calcium carbonate as a calcified atheroma model. An Mn-tpppt molecule, which is a manganese complex of a phosphorylated porphyrin derivative with twelve phosphonooxy groups, can be well absorbed on DCA.These results give some fundamental guidelines for developing a tissue-selective MRI agent.

众所周知，某些卟啉化合物可以吸附在癌性肿瘤或脂肪库上。它们的生物医学应用预计是PDT（照片动态疗法），X射线CT和MRI（NMR成像）的试剂。在这项工作中，合成了三种类型的水溶性卟啉，用于开发一种新的MRI血管造影剂，可以积聚成动脉粥样硬化。通过引入像烷基或荧光基团的液态/疏水量平衡的氧化碳蛋白衍生物，通过引入氧化型卟啉衍生物进行了合成。 MN-TSBP分子是一种具有四个硫苯基磺酰基的磺化卟啉衍生物的锰配合物，可以在早期的动脉粥样硬化瘤（DCA）上充分吸收，作为早期的动脉粥样硬化瘤模型，并积聚在使用兔子的实验中的正常主动脉壁上2-5倍的动脉瘤。并合成了体外和体内实验获得良好的相关系数（> 0.8）。合成了类型的氨基酸孢子菌素衍生物。但是所有产品都倾向于在水溶液中水解。通过体内的安全性，合成了三种类型的磷酸化卟啉衍生物，以及它们对动脉粥样硬化的钙化的吸附选择性。 Mn-TPPPD分子是一种具有八个磷酸基团的磷酸化卟啉衍生物的锰配合物，可以很好地吸收碳酸钙作为钙化的动脉粥样硬化模型。 Mn-TPPPT分子是一种具有十二个磷酸基团的磷酸化卟啉衍生物的锰配合物，可以很好地吸收DCA。这些结果为开发组织选择性MRI剂提供了一些基本指南。