Development of Porphyrin chelate for NMR imaging diagnosis agent

众所周知，一些卟啉化合物可以吸附在癌性肿瘤或脂肪库上。它们在生物医学上的应用有望作为PDT（光动力治疗）、x射线CT和MRI（核磁共振成像）的试剂。本研究合成了三种水溶性卟啉，用于研制一种新的磁共振血管造影剂。通过引入疏水基团如烷基、苯基或氟基来控制亲疏水平衡，合成了8种磺化卟啉衍生物。Mn-tsbp分子是一种含有四个亚砜联苯基的磺化卟啉衍生物的锰络合物，它可以在脱氧结肠酸（DCA）上很好地吸收，作为早期动脉粥样硬化模型，并且在兔的实验中积累到动脉粥样硬化的2-5倍于正常主动脉壁。体外、体内实验均获得较好的相关系数（>0.8）。合成了5种氨基酸卟啉衍生物。但所有产物在水溶液中都倾向于水解。考虑到其在体内的安全性和对动脉粥样硬化钙化的吸附选择性，合成了三种磷酸化卟啉衍生物。Mn-tpppd分子是一种具有8个磷酸氧基的磷酸化卟啉衍生物的锰配合物，可以很好地吸收在碳酸钙上作为钙化动脉粥样硬化模型。Mn-tpppt分子是一种具有12个磷酸氧基的磷酸化卟啉衍生物的锰配合物，可以很好地吸附在DCA上。这些结果为开发组织选择性MRI试剂提供了一些基本指导。

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.