¹⁸F-FDG PET/CT Imaging For Early Prediction Of Response To Endostar Therapy In A Mouse Xenograft Model Of Nasopharyngeal Carcinoma

Objective:1.To investigate the usefulness of ¹⁸F-FDG PET/CT imaging for early prediction the response to antiangiogenic therapy in a mouse xenograft model of nasopharyngeal carcinoma.2.To explore the effect of Endostar anti-angiogenesis on the expression of ELAM-1.Methods:0.1ml 5-8F(2.0×10⁷ ml^-1)cell suspension of nasopharyngeal carcinoma was injected into the back of the left hind limb of nude mice by subcutaneous transplantation.Twelve tumor-bearing mice were randomly divided into experimental and control group with six in each group.The status,growth rate and tumor size of nude mice were recorded.when the tumor volume reached about 100-300 mm³,The experimental group was given endostar（20mg/kg,once daily for 14 days）by intraperitoneal injection,while the control group received the same amount of saline at the same way.The ¹⁸F-FDG PET/CT scans were obtained after 14 days of treatment.Tumor-bearing mice received 200-300μCi of ¹⁸F-FDG.A region of interest（ROI）was manually drawn on the PET/CT fusion image to obtain the maximum standard uptake value（3D SUVmax）.the nude mice were sacrificed and tumor volume and tumor weight were measured to calculate the maximum injected dose percentage of ¹⁸F-FDG per gram of tumor（%ID/g max）.In addition,the tumor microvessel density（MVD）and ELAM-1 expression were examined by immunohistochemistry.The image was converted to grayscale image and highlighted the positive area by Image J software（V1.51）.And then the area of interest was selected.Quantitation was done using Image J software（V1.51）to reflect the expression level of ELAM-1.A completely randomized two-sample t test was used to compare the differences in tumor ¹⁸F-FDG uptake,nude body weight,tumor volume,MVD,and ELAM-1 expression in experimental and control groups.Pearson correlation analysis.was used to analyze the correlation between tumor absorption rate（%ID/g max）and ELAM-1 and MVD.Result:1.One week after inoculation,subcutaneous transplantation tumors were visible by unaided eye,and the tumor formation rate was 100%.As tumors enlarged,nude mice gradually decreased exercise,lose weight,and become less responsive,especially in the control group.2.The original weight of nude mice in the experimental group was18.35±1.05g and the control group was（18.75±1.09）g.There was no significant difference in the original body weight between the two groups of nude mice（t=1.061,P=0.337）.It took about one week that nude mice formed tumors after modeling.the tumor volume was markedly reduced at 14th day after endostar treatment（28th day after modeling）.The nude mice were sacrificed and tumor size were measured.The tumor volume in the experimental group and the control group was（3.526±1.50）cm³ and（2.581±0.692）cm³.There was no significant difference in tumor volume between the two groups of nude mice（t=1.497,P=0.185）.3.ELAM-1 was expressed in two groups of nasopharyngeal carcinoma xenografts,and was mainly expressed in endothelial cell membranes.The MOD value of the experimental group was smaller than the control group（0.269±0.02vs 0.359±0.07,t=3.078）.The difference was statistically significant（P=0.028）.4.MVD in experimental group was lower than that in control group（27.222±3.93 vs 43.722±14.88,t=3.058）.The difference was statistically significant（P=0.028）.5.The characteristics of 18F-FDG PET/CT imaging of transplanted tumors:¹⁸F-FDG did not show significant uptake in the tumor of experimental and control groups.Tumor was small difference from the development of the contralateral hindlimb of nude mice.Visually,The tumor uptake of five nude mice in the experimental group was lower than the contralateral,,and the tumor uptake of the remain was higher than the contralateral.In the control group,there were three xenograft tumors uptake higher than the contralateral,tow tumors of nude mice were lower than the contralateral and one was similar to the contralateral.6.The tumor ¹⁸F-FDG absorption rate（%ID/gmax）in the experimental group was significantly lower than that in the control group（3.17±0.42 vs6.84±0.47,t=8.505,P=0.003）.%ID/gmax has no significant correlation with ELAM-1 expression（r=0.537,P=0.072）.%ID/gmax has no significant correlation with MVD（r=0.534,P=0.074）.ELAM-1 expression has no significant correlation with MVD（r=-0.137,P=0.674）.Conclusion:Endostar can reduce the expression of ELAM-1 and MVD.¹⁸F-FDG PET/CT imaging can early predict the response to antiangiogenic therapy in a mouse xenograft model of nasopharyngeal carcinoma.The ability of reflecting the changes of the tumor microstructure is limited.