| As one of the powerful diagnostic imaging techniques, MRI could acquire information of the human body systematically and dynamically from the degree of molecule to the whole tissue with the advantage of non-radiation and non-invasion. In order to improve the accuration and flexation of the imaging, contrast agents are used by 30% in the clinical diagnosis nowadays. However, an ideal contrast agent should have high relaxivity, specific tumor location, high stable constant and low toxicity and so on. In recent years, the object of development is how to improve its contrast and specifity in the tissues. Many contrast agents were designed and exploited swiftly after the authorization of Gd-DTPA as the first contrast agent by FDA in the clinical application. Due to the appropriate biodistribution, biocompatiblity and tumor specifity, as a candidate ligand of metal, porphyrin had been studied in the PDT therapy and MR imaging. In our study, we had synthsized the porphyrin which were modified by DTPA systematically, meanwhile their application in the MRI as contrast agents were well verified. This study had a great significance for the further study in the clinical application.First of all, the aminized porphyrin skeleton was synthesized with THPP by the method of asymmetric nitration and reduction. After the acyling with DTPAA, the serried ligands were acquired by coordinating with GdCl3. Then the determination of the property of the sample Gd(L1),Gd(L2),Gd(L3),Gd(L4) under NMR and MRI separately, the relaxivity was characterized and compared, meanwhile, the MR imaging showed their ability to enhance the signal of image and the vivo distribution in the H-22 tumor model by MRI. The result showed that, the sample Gd (L1) and Gd (L4) possessed better solubility in water and more obvious MR imaging effect than the sample Gd (L2) and Gd (L3).Furthermore, after 2h of tail vein injection, the sample Gd (L4) showed the strengthest signal in MR imaging. By the comparation with the vivo distribution, the sample Gd (L1) had more specific in tumor than the Gd (L4) did. Compare the fluorescence imaging result, which was acquired by the excitation of the 465nm and the emission of the 700nm, the result is agree with the vivo distribution in MRI.Finally, in order to exploit molecular assemble effect of nanotube and the starch with contrast agent, the nanotube and the starch were assembled with sample Gd (L1) and Gd (L4). Simultaneously, the interaction between albumin and porphyrin was studied with CD and UV, which were important to explain the vivo distribution and the clinic application. In the study of the different carriers, we found that the Gd (L4) had the capability to disperse the nanotube in water by coordinating with nanotube and it showed that the compound had the effect of T2-weighted in MR imaging. At the other hand, due to the solubility of starch in water, it made the sample Gd (L1) had more soluble in water and strengther signal of T1-weighted in MR imaging after the mixaiton. Through the characterization with CD and UV of the albumin, it tuned out that Gd (L1) had the much intense energy to coordinate with ablumin. It was well to explain its long resortion in vivo distribution and made a great significance in the further study. |
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