Development of Porphyrin chelate for NMR imaging diagnosis agent

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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.