Preliminary Study On The Synthesis And Application Of MR Molecular Probe Based On Type ? Collagen For Mice Liver Fibrosis

Objective: Synthesize MR probes of type I collagen and use for liver MR imaging in mice to achieve qualitative diagnosis of liver fibrosisMethod:.Synthesis of type I collagen-binding peptides(LRELHLNNNG,TICTP)from various amino acids using the solid phase method and the synthesis of the crosslinker DOTA using the precursor epoxide vinegar using the organic small molecule total synthesis method,followed by the preparation of TICTP-DOTA The complex finally chelates cesium ions to obtain the peptide-DOTA-Gd complex TICTP1,and the chemical structure is confirmed using mass spectrometry analysis and NMR spectroscopy.Eighty Kunming mice were randomly divided into two groups,60 in the experimental group,and mice models of hepatic fibrosis were produced by intraperitoneal injection of carbon tetrachloride.Two mice were randomly selected on the first day after the weekly model establishment.After pre-scanning of MR liver T1 by tail vein injection of TICTP1,the liver tissue signal changes were observed.It was found that TICTP1 was significantly elevated in mice after 6 weeks of modeling,and the corresponding pathological phase was F3(METAVIR standard);Inject the same dose of PBS solution.Ten mice in the experimental group and 10 in the control group were randomly selected for each injection for 6 weeks.The experimental group and the control group were randomly divided into two groups,5 in each group.They were injected with TICTP1(0.5 ?mol/ml,1.5 ml/100 g weight).At the same dose of Magnevist,MR liver T1 was scanned at 5 min,60 min,120 min,and 180 min to dynamically observe the changes of liver signal and the signal ratio of liver tissue to the erector spinae of the same plane.At the same time,mouse liver tissue was taken for examination.Statistical analysis using SPSS 16.0.Result: 1.The peptide-DOTA-Gd complex TICTP1 was successfully synthesized and the results of mass spectrometry analysis were in agreement with expectations.2.Successful construction of pathological models of liver fibrosis in mice with different pathological stages.3.According to the results of preliminary experiments,F3 mice were tested qualitatively,and the T1 signal in the liver of the mice injected with the molecular probe TICTP1 was significantly increased.The mice liver was injected 180 minutes after the injection of the molecular probe TICTP1 in the F3 liver fibrosis group.The differences of MR signal changes and injections of Magnevistin group and normal control group were statistically significant(p<0.05).The area under ROC curve,sensitivity,and specificity were both 1.However,there was no significant change in liver T1 signal in the control group and the experimental group injected with Magnevist(p>0.05).Conclusion: 1.Successful synthesis of polypeptide-DOTA-Gd complex TICTP1.2.TICTP1 can be used as a MR molecular probe for mouse liver fibrosis specific imaging.