Study On Superparamagnetic Iron Oxide MR Contrast Agent

With the rapid development of liver surgery,the clinical diagnosis requires the imageology to detect the finer pathological changes of liver and identify them more accurately,relying on the research and the application of the magnetic resonance imaging（MRI） contrast agent,especially the MRI contrast agent of liver target. Superparamagnetic iron oxide（SPIO）is a new type of magnetic material used in the MRI,which can be developed as reticuloendothelial system（RES） MRI contrast agents. It shows a good signal to noise ratio and It is safe to use in application of MRI.Many research reports about it have been published abroad in recent years.In order to expand the application of MRI contrast agent in clinical studies,this paper explores how to prepare the hydro-based magnetic fluids（HMF） with the optimized technics.The stability and the safety of SPIO were investigated and the rat model of liver cancer was established and experimental research into the effect of enhanced MRI by SPIO was done.The procedures and findings were as follows:1.SPIO colloid was prepared with ferric chloride and ferrous chloride by chemical precipitation reaction.Total iron content was determined by phenanthroline photometry. Based on single factor studies,the L₉（3⁴） orthogonal test was conducted to optimize preparation technics of hydro-based MF.The stability of hydro-based MF was inspected by comparing particle size distributions of MF before and after sterilization according to the criteria of the SPIO colloid,its yield and specific magnetization.Thus the optimal manufacturing condition and formula were obtained by orthogonal design test.The experimental data showed that the best conditions for MF A₁B₂C₂D₂ should be 0.5mol/L concentration of NaOH by mixing Fe salt at 60℃for 30min,with the mass ratio of dispersing agent to Fe salt being 5:1.2.The physicochemical properties of SPIO were defined.Transmission electron microscopy（TEM） showed that SPIO particle was nanometer particle with the diameter of iron oxide crystal being approximately 15 nm;Laser scattering measurement showed the average diameter of SPIO was 18.4 nm（n=5）.The finding of X-ray diffraction confirmed that SPIO contained Fe₃O₄ crystal.The results of magnetometer measurement demonstrated the superparamagnetic property of SPIO,whose quality saturation magnetization reached 80.2emu/g Fe（n=5）.3.Stability and safety of SPIO were tested by experiments.The findings demonstrated that sterilization had little effect on the appearance,size and magnetic property of colloid.The properties and quality of the preparation remained the same after the acceleration test under the conditions of the strong light and high temperature or after six month of storage at the room temperature.The vessel stimulation and hemolytic experiment on domestic rabbits show that SPIO was safe and nonirritant.The n acute toxicity experiment on mouse showed tha LD_（50） was 177 mg/kg in mouse,about 316 times of the dosage for human.4.The effects of SPIO-enhanced MR was tested by using normal rats and rats with hepatic implanted tumor as subjects.By SPIO-enhanced scanning,it was found that the required median effective dose of SPIO for normal rats was 20μmol/kg.By plain scanning and SPIO-enhanced scanning 32 focuses of 28 rats with hepatic implanted tumor and comparing the respective images and contrast noise ratio of T₁ and T₂-weighted MRI before and after the injection of SPIO.It was found that signal intensity of normal liver tissue declined remarkably,while the signal intensity of liver tumor didn’t change and the optimal image of MRI can be obtained after 30 minutes of injection of SPIO.When the dose of SPIO reached 20μmol Fe/kg,the highest CNR of enhanced T₂-weighted images can be obtained,which almost doubled that of enhanced T₁-weighted images.The CNR of unenhanced T₁-weighted MRI was the lowest.