The Value Of CT Volume Perfusion On Evaluating The Efficacy Of Endostar On Rabbit VX2Soft Tissue Tumor

Ⅰ Establishment of Rabbit VX2Soft Tissue Tumor Model and CT Perfusion Imaging[Objective] To explore the establishment of rabbit VX2soft tissue tumor model and observe their growth characteristics and master the CT volume perfusion technology, which can provide experimental conditions for further study. To observe the tolerance of New Zealand white rabbits with treatment of Endostar.[Materials and Methods]0.03ml VX2tissue mass suspension was respectively injected into the bilateral thigh of4New Zealand white rabbits. CT volume perfusion imaging was performed after9days, once every other day, up to21days. The data were analyzed by VPCT body-tumor packages, and then the time-density curve of region of interest, the perfusion parameters and the corresponding pseudo-color images including blood flow, blood volume, mean transit time, permeability etc. were automatically generated. Endostar (3mg/kg) was injected into2rabbits by ear vein after15days, which selected by randomly, once every day until the last CT scans; the other2rabbits were given comfort treatment by saline. After all the scans, HE staining was conducted and the microscopic features of VX2tumors were observed.[Results]8lesions of VX2soft tissue tumor were successfully established. And enhanced nodules were seen at the ninth day, which less than1cm. Necrosis appeared accompanied by the tumors growth. The CT perfusion images were clear and had well repeatability. The BF, BV, PMB value of tumor region were significantly greater than normal muscle tissues (p<0.05), and the MTT value were significantly less than normal muscle tissue (p<0.05).The VX2tumors are white, fish-like masses with unclear boundaries. Coagulation or bleeding necrosis was common seen in the tumor. There are rich vascular around the tumor. VX2tumor cells grow invasively into the muscle gap nested or diffuse distribution, with irregular shape, large nucleus and less cytoplasm. There are less interstitial in the tumor, but vessels in the interstitial are rich.[Conclusion] Tissue mass suspension injection is a good method to build VX2soft tissue tumor models, which is easy and has high successful rate and forms isolated tumor nodule. The tumors grow steadily during9～15days after transplant, there is relatively less necrosis during this time, when is suitable for CT perfusion imaging. The CT perfusion images were clear and the BF, BV, PMB values of the tumor region were significantly greater than normal muscle tissues and the MTT values were significantly lower than normal muscle tissue. The time-density curve of tumor is rise-platform type. Endostar (3mg/kg) can be tolerated by New Zealand white rabbits and there are no adverse reactions.Ⅱ The value of CT volume perfusion on evaluating the efficacy of endostar on rabbit VX2soft tissue tumor’[Objective] To explore the impacts of Endostar treatment on the growth of rabbit VX2soft tissue tumor and to find the changes of CT volume perfusion parameters (BF、BV、MTT、PS etc.) before and after treatment of Endostar and the corresponding pathological changes. Further to investigate the value of CT volume perfusion on clinical evaluation of solid tumors in order to provide experimental basis for treatment options and prognosis of clinical patients.[Materials and Methods]20rabbit VX2soft tissue tumor models were established by tissue mass suspension injection. Then divided them into2groups, that is Endostar treatment group and control group,10in each group. CT volume perfusion imagines were conducted at9days,11days,13days and15days after transplantation. Two rabbits of each group were executed randomly after each scan. Tumors were removed and fixed by formaldehyde, then HE staining and immunohistochemistry staining of CD31, VEGF were conducted to count the expression of micro vessel density and vascular endothelial growth factor. Statistical software SPSS16.0was used to find out the difference of the values of perfusion parameter between groups and correlations between perfusion parameters and MVD. There was statistically significant when p<0.05.[Results]20lesions of VX2soft tissue tumor were successfully established. Statistics show that tumors of treatment group grew slower than control group, there are statistically differences after4days cure by Endostar (p<0.05). The PMB values of treatment group are larger than those of control group at2days,4days, and6days after treatment (p<0.05). The MVD of both groups increase gradually with time, but the MVD of treatment group increased slower than control group. The expressions of VEGF of2groups at different time points are both strong positive. Pearson correlation analysis showed that BF, BV values were positively correlated with MVD (p<0.05) and there are no correlations between MVD and MTT, PMB (p>0.05).[Conclusion] The growth of VX2tumors can be inhibited by Endostar, which can delay the speed of necrosis meanwhile. The PMB values increased by Endostar treatment and PMB values could be used as a sensitive indicator of early efficacy assessment. There are positively correlation between MVD and BF, BV values, which could be used to evaluate angiogenesis status but not not suitable for efficacy assessment.