Studies On Soluble Paramagnetic Metal Complexes With Ligands From Diethylene Triamine Pentaacetic Acid And Hydrazide As Potential MRI Contrast Agent

Magnetic resonance imaging (MRI) is at present well established as a safe and efficient imaging technique for the human body in clinical diagnosis. Therefore, studying MRI contrast agents is more important. Several types of paramagnetic metal ion-chelate complexes with various ligands have been proposed for use as contrast-enhancing agents in MRI. Gd (DTPA)~2- was well-established contrast agent in clinical use for MRI due to its high relaxivity, high chemical stability and low toxicity. However, its passive and nonspecific distribution in vivo limits its utility in focal lesion detection and, moreover, its ionic characteristic leads to some side effects associated with its hyperosmolality at clinical dose. So, it has been one of both the most attractive and challenging tasks in this area in attempts to decrease the side effects and improve the tissue-and/ or organ-specificity.The interest of the dissertation is chiefly concentrated on soluble paramagnetic metal complexes with ligands from diethylene triamine pentaacetic acid and hydrazide as potential MRI contrast agent.In this paper, eight series of novel ligands and their soluble paramagnetic metal complexes have been synthesized and characterized. Relaxivity of paramagnetic metal complexes with these ligands were measured by aninversion-recovery pulse sequence.The paper is divided into four parts:(1) It was given a brief review of the research progress in the MRI contrast agent.(2) Eight kinds of ligands have been synthesized from DTPA and hydrazides. All ligands obtained were characterized with elemental analyses, ~1H NMR, FAB-MS, thermal analyses and IR methods.(3) Soluble paramagnetic metal complexes have been synthesized. The composition and structure of all these complexes were characterized with elemental analyses, thermal analyses, molar conductivity and IR methods.(4) Studies on soluble paramagnetic metal complexes with ligands fromdiethylene triamine pentaacetic acid and hydrazide as potential MRI contrast agent. Relaxivity of paramagnetic metal complexes with these ligands were measured by aninversion recovery pulse sequence. The results showed that the spin-lattice relaxivity of Gd complexes are the best in all rare earth complexes and the spin-lattice relaxivity of Mn complexes are the best in all transition element complexes. It is accordant with the literature. It also showed that the spin-lattice relaxivity of complexes were different to depend on introduced molecule fragment in DTPA, the sequence of the spin-lattice relaxivity of Gd complexes is p-hydroxybenzoyl hydrazine ^ o-hydroxybenzoyl hydrazine >/?-methylbenzoyl hydrazine > benzoyl hydrazine > isoniazid, and the conclusion is also in agreement with Mn complexes. All new ligands in this paper is as following:1. Diethylenetriamine-N, N" -bis (acetyl-/>-hydroxybenzoyl hydrazine ) -N, N' , N" -triacetic acid2. Diethylenetriamine-N, N" -bis (acetyl-o-hydroxybenzoyl hydrazine) -N, N' , N" -triacetic acid3. Diethylenetriamine-N, N" -bis (acetyl-^-methylbenzoyl hydrazine) -N, N' , N" -triacetic acid4. Diethylenetriamine-N, N" -bis (acetyl-benzoyl hydrazine) -N, N' , N" -triacetic acid5. Diethylenetriamine-N, N" -bis (acetyl- isoniazid)-N, N', N" -triacetic acid6. Diethylenetriamine-N, N',N" -tri(acetyl-/j-methylbenzoylhydrazine)-N,N - bisacetic acid7. Diethylenetriamine -N, N', N" -tri (acetyl-benzoyl hydrazine) -N, N" -bisacetic acid8. Diethylenetriamine -N, N', N" -tri (acetyl-isoniazid) -N, N" - bisacetic acid...