ABSTRACT
Objective To evaluate the response of the lung tumor xenografts in nude mice to antiangiogenic treatment from perspectives of anatomic,vessel function,cellular and molecular level using the multimodality imaging techniques including optical imaging,dynamic contrast enhanced MRI(DCE-MRI)and diffusion weighted imaging(DWI).Methods The green fluorescent protein(GFP)was transplanted labeled using GFP-expressing NCI-H460 cells.After the transfection of GFP,NCI-H460 cells were implanted subcutaneously into nude mice.Ten days after implantion,12 nude mice whose tumor xenografts grew to 0.5-1.0 cm in the maximum diameter were randomly divided into 2 groups,and injected with phosphate-buffered saline and recombinant human endostatin respectively.Then the nude mice in the two groups underwent optical imaging,DCE-MRI and DWI.The volumes,photon counts,the quantitative MR vessel functional parameters including volume transfer constant(Ktrans),rate constant(Kep),volume of extravascular extracellular space(Ve)and maximum area under the enhancement curve(iAUC),and apparent diffusion coefficient(ADC)values of the tumors were recorded.Then tumors were collected and observed using the transmission electron microscopy and pathology examination,including HE staining,microvessel density(MVD)and the expressions of vascular endothelial cell growth factor(VEGF).The Kep and VEGF expressions in experimental group and control group were compared with x2 text,and other values were compared with t test.The Pearson and Spearman test were used for analyzing the correlation of values in the two groups.Results Seven days after inoculation,the fluorescence signals were detected and grew with the growth of the tumors.On the 7 day after starting therapy,the photon counts of experimental group and control group were(2.51 ± 2.43)× 1010(photon/sec)and(5.77 ± 3.25)× 1010(photon/sec),respectively with no significant differences(t =1.964,P ＞0.05).Two sample t test showed that the tumor volumes in experimental group were smaller than those in control group[(365 ± 56)vs(987 ± 265)mm3,t =0.001,P ＜ 0.01].There was a positive correlation(r =0.673,P ＜ 0.05)between the photon counts and the volumes of the tumors.The mean Ktrans,Kep,Ve and iAUC of experimental group were:(0.055 ±0.012)min-1,0.335(0.184—0.894)min-1,0.297 ± 0.041 and 7.334 ± 3.930,and those for control group were:(0.117 ± 0.027)rin-1,0.417(0.324-1.736)min-1,0.326:±:0.062 and 13.280 ± 4.245.There were significant differences of Krans and iAUC(t =5.155,2.518,P ＜ 0.05)between experimental group and control group.And there was a positive correlation(r =0.715,P ＜ 0.0 1)between the values of iAUC and MVD,but not the expressions of VEGF(r =0.484,P ＞ 0.05).The values of ADC in experimental group were higher than that in control group[(791 ± 38)× 10-6 vs(737 ± 43)×10-6 mm2/s],and there were significant differences(t =-2.299,P ＜ 0.05).Two sample t test showed that the MVD in experimental group were lower than that in control group[(11.9 ± 4.8)vs(19.2 ±4.3)item/hpf,t =2.774,P ＜ 0.05].The VEGF expressions in experimental group were lower than that in control group(x2 =4.000,P ＞ 0.05).It was observed that some cells in experimental group had degenerated and apoptotic signs by the electron microscopy.Conclusions Evaluating the response of lung tumor xenografts to antiangiogenic treatment at anatomical,vessel functional,cellular and molecular level using the multimedality imagings is applicable.And it will be in favour of evaluating the therapeutic effect promptly.