The Study On Lymphatic System–targeted Contrast Agent In Magnetic Resonance Imaging

MRI (Magnetic Resonance Imaging, MRI) technology has a pivotal position in medicinal imaging diagnosis. The spin atoms are bombarded with certain radio frequency under the constant external magnetic field, make their excitation produce relaxation phenomenon, and collect them for MRI signals. In order to enhance the signal contrast between normal tissue and diseased tissue, improve image clarity and disease detection rates, there are increasing use of MRI contrast agents clinically. Selectivity, solubility, safety and stability will be the future trend of contrast agents with the rapid development on the research.This paper chose dextran 40 and sodium alginate as the carrier respectively, aimed to synthesize contrast agent with high MRI signal intensity and the lymphatic system targeted. Macromolecular conjugates of Dextran-DTPA-Gd were synthesized in two methods. Dextran reacted with DTPA anhydride using DMAP as catalytic agent in No.1 Method, Dextran reacted with DTPA using DMAP-EDC·HCl as catalytic agents in No.2 Method. The best reaction conditions ( the molar ratio of Dextran to DTPA was 1:1.5, the temperature and time of the reaction were 50℃and 48 h ) were obtained by comparing the weight content of Gd and water-solubility of the products. The product with higher content by weight of Gd (16.1%) and good water-solubility was obtained and characterized by FTIR and particle size analysis (Size distribution ranged from 100nm to 150nm, 130nm in average). The higher gadolinium content and water-soluble polymer contrast agent was obtained finally, and appropriate for animal experiments. Macromolecular conjugates of Algin-DTPA-Gd were synthesized in two methods. In No.1 Method, sodium alginate was acidified into alginate acid which was then reacted with DTPA anhydride using DMAP as catalytic agent. In No.2 Method turned sodium alginate into propylene glycol alginate which reacted with DTPA using DMT-MM as catalytic agent. The product Algin-DTPA-Gd with higher content by weight of Gd (15.6%), good water-solubility and low pH (pH < 3)was obtained from No.2 Method, Algin-DTPA-Gd was characterized by FTIR and particle size analysis (Size distribution ranged from 38 nm to 135 nm, 108 nm in average).The New Zealand rabbits were used in animal tests. Dextran-DTPA-Gd and Magnevist were injected into No.1 rabbit's right and left legs respectively at the interval of 30 min after the 3D Fast TOF-SPGR CE-MRA sequence scan. Dextran-DTPA-Gd was injected into No.2 rabbit's both right and left legs simultaneously. The scan interval of two experiments are 10, 20, 25, 30, 35, 40, 45, 50, 55min, 1, 4 and 24 h. The MRI pictures of Dextran-DTPA-Gd were evaluated in comparison with the MRI pictures of Magnevist. The signal intensities of the regional lymphatic system were qualitatively assessed by the Time-Enhancing Rate Curve. The MRI of No.1 and No.2 rabbits were compared also. The results indicated that Dextran-DTPA-Gd obviously had higher signal enhancement than that of Magnevist, and had lymphatic system targeted property.