Metabolism And MR Imaging Study Of Gd-DOTA Coupled Lithocholic Acid In Healthy Murine

Objective（s）:To synthesize a novel MRI hepatobiliary specific contrast agent Gd-DOTA-lithophanic acid（LCA）and conduct a comparative study with gadoxetic acid disodium（Gd-EOB-DTPA）to explore its clinical application potential.Methods:1.Design and synthesis of novel MRI contrast agent Gd-DOTA-LCA,characterized by mass spectrometry.2.Five equal concentration gradients of Gd-DOTA-LCA and Gd-EOB-DTPA solutions were configured,and T1 relaxation rates were measured and compared by MRI scanning.Healthy rats（n=6）were injected with Gd-DOTA-LCA intravenously,and their bile and urine were collected to measure Gd³⁺concentrations for calculating the hepatobiliary-renal excretion ratios.Healthy mice were randomly grouped and performed 12-phase dynamic enhancement scan with Gd-EOB-DTPA（n=6）and Gd-DOTA-LCA（n=6）（interval of 5 min each phase）;the liver,gallbladder and bladder signal intensity were measured to plot time-signal intensity curve and calculate semi-quantitative indexes（maximum signal intensity,peak time,maximum slope）.These indexes were statistically compared,and P<0.05 was considered statistically significant differences.Results:1.The novel MRI contrast agent Gd-DOTA-LCA was successfully synthesized with 86%yield and the mass spectrometer analysis results were consistent with the theoretical molecular weight（1067）.2.The T1 relaxation rate of Gd-DOTA-LCA（1.52）was slightly higher than Gd-EOB-DTPA（1.49）.3.The hepatobiliary and renal excretion ratio of Gd-DOTA-LCA was about 8.7:1.2.4.The enhancement trend of liver in Gd-DOTA-LCA and Gd-EOB-DTPA was similar,while the enhancement trend of gallbladder and bladder in Gd-DOTA-LCA was slightly lower than Gd-EOB-DTPA（P<0.05）.The maximum signal intensity of liver and bladder and the maximum slope of gallbladder in Gd-EOB-DTPA were higher than Gd-DOTA-LCA（P>0.05）.Conclusion（s）:In this study,we established a synthetic route of a novel hepatobiliary contrast agent Gd-DOTA-LCA with high T1 relaxation rate,good hepatobiliary targeting and similar in vivo distribution to Gd-EOB-DTPA.