Preparation Of Iron-based Magnetic Resonance Imaging Contrast Agents And Their Application For Tumor Diagnosis

Tumors are still the main cause of human death in the world,and tumors have a strong concealment in the early stage.Most of the patients are diagnosed as advanced patients.The cure rate of advanced patients is generally not high,and the existing medical means can only prolong their life cycle as far as possible.Fortunately,the early cancer patients are likely to be cured.Therefore,if the early diagnosis efficiency of cancer can be improved,the survival rate of cancer patients can be greatly improved.Magnetic resonance imaging(MRI)is a commonly used clinical diagnostic method,which can be used for the diagnosis of tumors.Contrast agents(CAs)can improve the sensitivity of MRI,and thus improve the efficiency of tumor diagnosis.Therefore,in order to overcome the problems of commercial T1 contrast agents based on Gd chelates,commercial T2 contrast agents based on magnetic iron oxide nanoparticles(MIONs)and reported T1 contrast agents based extremely small MIONs(ES-MIONs),in this thesis,we successfully synthesized two kinds of contrast agents based ES-MIONs with good water dispersibility by a simple coprecipitation method.The main contents are given below.(1)y-Polyglutamic acid(y-PGA)was used as a stabilizer to synthesizeγ-PGA-ES-MIONs.After optimization of the synthesis conditions,the r1 value at 3.0 T of γ-PGA-ES-MION6 is 5.7±0.1 mM-1 s-1,and the r2/r1 ratio is 12.3±0.4.Laser scanning confocal microscopy(LSCM),flow cytometry and MRI images indicate that the y-PGA-ES-MION6 is easy to be uptaken by cells,and the MTT assay demonstrate the ideal biosafety of y-PGA-ES-MION6.(2)In order to obtain ES-MIONs with better T1-weighted imaging ability,PASP-ES-MIONs were synthesized with sodium polyaspartic acid(PASPNa)as a stabilizer.After optimization of the synthesis conditions,the MRI ability of PASP-ES-MION9(3.7 nm)is better than the above-mentioned γ-PGA-ES-MION6,with a higher r1 value(7.0±0.4 mM-1 s-1)and a lower r2/r1 ratio(4.9±0.6)at 3.0 T.The excellent water dispersibility of PASP-ES-MION9 comes from the-COOH of the stabilizer PASPNa.The pharmacokinetics and biodistribution of PASP-ES-MION9 in vivo indicate the better tumor targetability and MRI time window of PASP-ES-MION9 than commercial Gd chelates.The Ti-weighted MR images of aqueous solutions,cells and tumor-bearing mice at 3.0 T or 7.0 T demonstrate the stronger capability of enhancing the MRI contrast of PASP-ES-MION9 comparing with the commercial Gd chelates.The MTT assay,live/dead staining of cells,and H&E staining show the excellent biocompatibility and biosafety of our PASP-ES-MION9.Consequently,the biocompatible and biodegradable PASP-ES-MION9 with excellent water-dispersibility is an ideal T1-weighted contrast agents,and has the possibility of replacing clinical gadolinium chelates to achieve clinical transformation.