| Background:Hepatocellular carcinoma (HCC) in the clinical diagnosis of cancer cases showed strong growth trend, the mortality rate is the highest mortality of cancer in the third, currently has more than a million around the world each year the number of cases, seriously endangering the human health, causing great losses to the global economy. The traditional imaging methods and laboratory examination is difficult to realize the early diagnosis of hepatocellular carcinoma, metastasis and curative effect of prompt detection. The rapid development of nanotechnology and molecular imaging provides a new way. Among them, the target is a key molecular imaging research. To find effective target, and the development of new targeted drugs is the focus of medical research. CD147 is a can in the high expression of hepatoma cell surface transmembrane glycoprotein, can regulate tumor cell proliferation and induction of matrix metalloproteinases (MMP)metalloprotei-nase and MMP secretion, promote the invasion and metastasis of HCC cells, and participate in the formation of vascular growth and drug resistance of HCC. This study intends to through the induced Wistar rat model of hepatocellular carcinoma (HCC) based in low concentration of ethyl nitrite amine (Dena, Diethylnitrosamine), in the rat using CD147-USPIO (cluster of differentiation 147-Ultrasmall superparamagnetic iron Oxid) target to contrast agent, the liver of MR (magnetic resonance image) molecular imaging, enhances the dynamic observation and pathological control, study of CD 147 in HCC specific target to imaging and general distribution.Objective:Establish Wistar rat models of hepatocellular carcinoma and in MRI scans, in rats using target CD147-USPIO contrast agents to observe rat hepatocellular carcinoma magnetic resonance target to imaging, liver biopsy pathology and CD147-USPIO target contrast agent in liver of rats with roughly the time distribution changes.Methods:Every other day with freshly prepared diethylnitrosamine (DENA) solution (concentration of 0.1 mg/ml), respectively, to 18 Wistar rats (male) free drinking, feeding after 16 weeks change blank drinking saline. Rat model of hepatocellular carcinoma (HCC) to be established, from selection of molding and have better for experimental observation of 10 rat model of hepatocellular carcinoma (HCC), were divided for 2 groups,5 rats in each group, and is labeled accordingly into the experimental group and the control group. First of all rats in the two groups before MR scan, and then injected into the experimental group CD147-USPIO (experimental group), the control group injected USPIO (control group), and then injected into the drug enhanced scan after 1h,2h,4h,12h,24h T2WI, to observe the signal intensity of lesions on the image changes the signal intensity of image, hepatocellular carcinoma, liver tissue was measured after enhancement, the enhancement of the relative noise before and after tumor to liver ratio is calculated based on measured data (CNR), HCC tissue signal intensity in each time point value (SI), to observe the signal intensity of the tumor area at any time to change; the rats were sacrificed after scanning liver cancer specimens, HE staining was observed after cell distribution, Prussian blue staining after verification of iron content distribution and CD147 immunohistochemistry tissues the expression of CD147 in hepatocellular carcinoma view.Results:MRI scan of liver parenchyma showed multiple sizes of high or slightly high signal and mixed signal nodules on T2WI sequence. Select the diameter over 3mm nodules as the research object. The lesion boundary clear, most of the signal more evenly.(1) in before and after injection CD147-USPIO of contrast agent, that is, plain and 1 hour after injection of MR scanning, experimental rats liver tumor CNR is 2.78±0.35 and 2.16± 0.15, the difference has statistical significance (P< 0.05); while the control group rats were injected with USPIO and liver tumor CNR for 349±0.61 and 3.72±0.56, the difference is not statistically significant (P> 0.05).(2) from each time point of view, experimental group were injected CD147-USPIO contrast agent 1-2h tumor tissue signal intensity on T2WI decreased significantly less, in 2-4h tumor signal with the passage of time and gradually becomes low, tumor in 4h appeared a peak enhancement, and 12-24h signal of tumor showed an upward trend. The control group after injection of USPIO, the signal at each time point of tumor tissue with no significant reduction trend gently. The signal strength difference between the experimental group tumor is more obvious, with statistical significance (F=4.38, P<0.05). The signal intensity of tumor control group values have no obvious difference, not statistically significant (F=0.42, P> 0.05).The pathological results of HE staining showed that the lesions were observed as MRI confirmed hepatocellular carcinoma. Prussian blue iron staining showed that blue particles deposited in the cytoplasm of the tumor cells in the experimental group and the clearance of the cell, the control group tumor cell cytoplasm stained particle deposition rarely. CD147 immunohistochemical staining showed that cell membrane and cytoplasm in expression of CD147.Conclusion:1) of Wistar rat induced by DENA modeling method, simple and convenient operation, high rate of tumor formation.2) enhanced target CD147-USPIO to contrast agent in the liver of rats have gathered, showing that the signal of tumor tissue decreased significantly, although liver tumor contrast to noise ratio decreased, fuzzy edge of focus of a disease, but useful for targeted imaging and qualitative diagnosis of liver cancer.3) by MR dynamic scanning at each time point were observed CD147-USPIO enhanced after the tumor signal change, infer its distribution changes in tumor tissue. Enhanced 2-4 h tumor with the passage of time, a persistent enhancement,4H nanoparticles accumulation in the tumor target peak,12h after gradually withdraw. |
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