Value of targeted MR molecular imaging in evaluating the early efficacy of anti-angiogenesis drugs
10.3760/cma.j.issn.1005-1201.2015.06.006
- VernacularTitle:经MR靶向分子成像判断抗肿瘤血管药物早期疗效的价值
- Author:
Shuang DING
;
Jing WANG
;
Yonghua XU
;
Wenxiao JIA
;
Lixia YANG
;
Zili HUANG
;
Xiaodong PAN
- Publication Type:Journal Article
- Keywords:
Magnetic resonance imaging;
Angiogenesis inhibitors;
Comparative study
- From:
Chinese Journal of Radiology
2015;(6):419-424
- CountryChina
- Language:Chinese
-
Abstract:
Objective To assess the value of noninvasive MR imaging biomarkers in evaluating the early efficacy of anti?angiogenesis drugs. Methods Subcutaneous colon cancer xenograft models in thirty nude mice were established. The mice were randomly divided into three groups (n=10 for each): avastin injection group (dose 10 mg/kg), fluorouracil group (dose 150 mg/kg), physiological saline group (dose 20 mg/kg). Dynamic contrast?enhanced (DCE?MRI) and multiple b value diffusion weighted imaging (muti?b?value DWI) were acquired before or 1 h, 24 h and 48 h after the treatment. The parameters of contrast transfer coefficient (Ktrans), reflux constant (Kep), plasma volume fraction (Vp), extravascular extracellular volume fraction (Ve) and various apparent diffusion coefficients (ADCs) (ADC10b, ADChigh and ADCperf) were measured. Forty eight hours after the treatment, the mice were sacrificed following MRI. Aimmunohistochemical examination determined microvessel density (MVD) and proliferating cell nuclear antigen (PCNA) score. A repeated measures analysis of variance was used to compare the difference between the quantitative parameters among the three groups. A multivariate variance analysis was performed to compare the difference between the parameters at the same time point among the three groups. The correlation between MRI quantitative parameters with MVD and PCNA score were analyzed by Pearson and Spearman correlation analysis respectively. Factor analysis method summarized MRI quantitative parameters. Results One hour after the treatment, the parameters of Ktrans, Kep, ADC10b, ADChigh and ADCperf value immediately changed, they were(0.009 ± 0.005)/s,(0.042 ± 0.031)/s,(0.043 ± 0.002)× 10?3 mm2/s,(0.031 ± 0.005)× 10?3 mm2/s,(0.089 ± 0.006)× 10?3 mm2/s, Ktrans, Kep, ADC10b and ADChigh values all had significant differences in the three groups (F=42.058, 25.979, 9.870 and 8.511, respectively, all P<0.05). There were also statistical difference in the change trend of the above parameters among the three groups (F=22.108, 7.280, 65.698 and 19.900, respectively, all P<0.05). The change trend of ADCperf showed significant difference among the three groups (F=38.780, P<0.01). Ktrans, Kep and ADCperf positively correlated with the MVD count and PCNA score (r values were 0.421 to 0.811, both P<0.01), while ADC10b showed a negative correlation (r=-0.656 and-0.560, both P<0.01), ADChigh had negative correlation with the PCNA score (r=-0.568, P<0.05). Ktrans, Vp, Kep and ADCperf were classified as tumor microcirculation factor, whereas ADC10b and ADChigh were normalized for cell metabolism factor through the factor analysis. Conclusions Combination of DCE?MRI and muti?b?value DWI can reflect the early changes of drug therapy from the aspects of tumor microcirculation and cell metabolism. Ktrans, Kep, ADCperf, ADC10b and ADChigh can be taken as noninvasive imaging biomarkers to quantify the early efficacy of anti?angiogenesis drugs.
