Synthesis And Property Of MRI Contrast Agents Based On Gd-DTPA Modified By Nitrogen Heterocycles

Magnetic resonance imaging(MRI) is a new imaging technique, which is based on the principles of nuclear magnetic resonance and the addition of a linear gradient field spatially encoding to magnetic core, whereby the location of observing nuclear and its corresponding magnetic resonance signals. Currently, MRI has become an important diagnostic tool, which is widely used in clinical medicine. Contrast agents are an unique part of MRI which can modified certain parameters of the imaging core and increase the image contrast. Some contrast agents which have been used in clinic at present are short of high relaxation rate and organ-selectivity and other shortcomings. In order to conquer these defects, Contrast agents was modified by ligand structure, which can improve the efficiency of imaging and organ-selectivity. The main work is as follows:(1) The principle of MRI technology was sketched; Contrast mechanism, classification and factors of MRI contrast agents were reviewed; The research progress in several important class of MRI contrast agents were elaborated;(2) By introducing hydrophobic group of phenyl and 1,3,4-oxadiazole and 1,2,3-triazole to modify DTPA, four kinds molecular MRI contrast agent ligands of A, B, C, D and their cobalt complex were synthesized; By introducing glycine and its derivatives to modify DTPA, two metal-sensitive MRI contrast agent ligand of E, F and their cobalt complex were synthesized; By introducing hydrophobic of phenyl group to modified DTPA, three multi-nuclear MRI contrast agents ligand of G, H, I their cobalt complex were synthesized. Totally three nine kinds of contrast agents were synthesized, nine new Gd-DTPA-based contrast agents target molecule;(3) The new compounds and Gd contrast agent ligands were further characterized by at least four kinds of instruments. The relaxivity of Gd-A ~ Gd-G were measured. The toxicity in living animals of contrast agent Gd-A, Gd-I was studied, which have higher efficacy of relaxation. The results show that the relaxation of synthesized contrast agent of Gd ligands is higher than the clinical application of Gd-DTPA. Gd-A,Gd-I have no acute toxicity. The live animal experiments of Gd-A, Gd-I shows that contrast agent Gd-A, Gd-I have a large and strong enhancement, which have development and application prospects.(4) Contrast agent Gd-F was tested the aspects of metal-sensitive. The result shows that it has a strong metal-sensitive to Mg2+、Fe3+、Cu2+.