Synthesis Of Nanoparticles As A Contrast Agent For CT And Application In Imaging

Objective:To synthesize a new type of nanometer CT photo agent of Yb(OH) CO3andverify its characteristics. The toxicity, the distribution and the metabolism ofYb(OH)CO3in mice were detected, the imaging results were compared with orwithout the application of Yb(OH) CO3in order to provide a new product ofYb(OH)CO3as a new CT Contrast Agent for clinical application.Materials and methods:(1) Yb(OH)CO3nanoparticles are the process of well-prepared base ofprecipitation on urea homogeneous. It is an ideal solution of500ml of the totalvolume that the Yb(NO3)3·5H2O(7.5mmol) and urea(15g) dissolved in demonizedwater in2hours at room temperature, so as to achieve uniformed solution. Theuniformed solution was incubated in oil under the condition of90℃for3hours.Then, the suspension was centrifugated to get the white pellet, followed by soxhletextraction, i.e., the white powder was washed with deionized water for3-4times,then washed with ethanol for3-4times, the sample was kept in60℃vacuum ovenfor further usage. Using scanning electron microscope(SEM), transmission electronmicroscopy(TEM) and X-ray diffraction(XRD) to analyze the characterizations ofsamples.(2) For the experiment of toxicity in vitro, applying the MTT method to thevitro cytotoxicity experiment. Using Bio-Rad model-68to measure the Microplateabsorbance of wavelength of570nm, and analyzing the rate of vitality and viabilityof cell. To observe vitro cell morphology, HepG2cells can be made into single cellsuspension. The UV Vis absorption spectra can be used to analyz hemolysis in virto.(3) The vivo experiments on animals.12mice randomly chosen are divided intotwo groups: one is injected with Yb(OH) CO3as the experimental group, the other is injected with normal saline as matched group.30days later, the two group mice aresacrificed for histological.Then analysis the toxicity of mice in vivo which injectedwith Yb(OH) CO3.(4) To evaluate the efficiency of computed tomography(CT) in vitro imaging.Diluting the different concentrations of Yb(OH) CO3nanoparticles dilution andiobitridol into the PBS solution containing1%agarose by using Philips256slicespiral CT to scan.(5) In vivo evaluation of CT image, using Philips256slice spiral CT to scan inmultiplanar reconstruction(MPR) method for usage of original axial thin sliceimages to built coronal images. The result was calculated by CT value.(6) The experiment of contrast agent of vivo distribution and metabolism. Invivo distribution, with the injection of Yb(OH)CO3contrast agents, mice aresacrificed at different time points and extracted the main organ for quantitativeanalysis of ytterbium(Yb) particles. Using ICP-MS analysis to obtain liquid. Theexperiment of metabolism can also be used as ICP-MS to analyze urine and fecesobtained from mice.Result:(1) Yb(OH)CO3is successfully prepared and represented the characterization ofform and appearance. From scanning of Yb(OH)CO3nanoparticles in electronmicroscopy images, you can clearly see the smooth of surface of nanoparticlessample and roughly the form of same spherical of single scattered.(2) MTT showed that more than91%of the cells can still survive after48hoursof training in the presence of nanoparticles. It is not affected that the normal growthof cells on the surface of cell morphology was observed in vitro in the presence ofnanoparticles. It is showed that in vitro hemolysis experiment using Yb(OH) CO3(1mg NPs/mL) in high dose under the conditions is no hemolysis.(3) The experimental group and the matched group in all mice are killed after30days in the feeding and extraction of organ. And they are not observed in thepresence or absence of tissue injured as well as any other effects of Yb(OH)CO3nanoparticles.(4) The mice with Yb(OH)CO3sacrificed at various time points, after the discovery of ytterbium particles, are mainly gathered in the reticuloendothelialsystem, such as liver and spleen. The result with CT image is consistent. Injection ofcontrast agent in1,3,5,7days after the collection of urine and feces are found inhigh concentration Yb particles.(5) CT imaging and the value of CT, with the Yb(OH)CO3and iodine increasedCT than alcohol concentration gradually increased, showed a good linearrelationship with the concentration of the contrast agent. But at the sameconcentration, the conditions of measurement of Yb(OH)CO3ray absorption wassignificantly higher than the measurement of iobitridol X-ray absorption. The liverand kidney of two groups of mice in CT values are not statistically different. After30minutes injection of contrast agent, Yb(OH)CO3group are significantly higher thanthe liver CT iobitridol group, while Yb(OH)CO3groups of kidney CT are lower thanthe iodine has statistical significance than alcohol group. After three minutesinjection of contrast agent of iodine contrast agent, alcohol group had gathered onthe kidney, and after30minutes, the contrast agent almost gathered in urinarysystem in all. Time delayed up to2hours after, the liver CT value of Yb(OH) CO3isalmost3times than the iodine alcohol group, while the vale and scan of renal CTwith comparison does not change.Conclusion:(1) A new nano CT contrast agent, Yb(OH)CO3with low toxicity and goodhistocompatibility has been successly synthesized and characterized.(2) The study of Yb(OH) CO3in CT imaging in vitro and in vivo experimentsverified that an obvious advantage of Yb(OH) CO3contrast agent with a promisingclinical application.