病灶糖酵解总量变化对兔VX2肿瘤放疗反应的早期预测价值

Value of total lesion glycolysis change for early assessment of radiotherapy response in VX2 tumor bearing rabbit models

目的 探讨18 F-FDG PET/CT代谢参数对兔VX2肿瘤放疗敏感性的早期预测价值.方法 采用瘤块皮下种植法建立兔VX2肿瘤模型,将28只新西兰大白兔采用随机数字表法分为放疗组（n=21）和对照组（n=7）,放疗组给予单次剂量为20 Gy的放疗,并分别于治疗前1d及治疗后第7天行18F-FDG PET/CT检查;对照组于相同时间点进行相应检查.具体观测参数包括SUVmax、MTV和TLG.计算各参数的变化率（△SUV、△MTV和△TLG）.显像结束后取肿瘤组织行组织病理学分析,计算肿瘤细胞坏死率、炎性细胞浸润率及细胞增殖核抗原Ki67阳性率.按放疗后第7天的肿瘤体积变化状况,将放疗组分为放疗抵抗组和放疗有效组,组间比较采用Mann-Whitneyu检验;组织病理学参数与△TLG间的相关性采用Pearson相关分析.结果 放疗后第7天,放疗抵抗组（n=12）与有效组（n=7）比较,△MTV差异无统计学意义[（51.0±52.0）％和（23.0±47.0）％;u=44.0,P＞0.05];而△SUV[（10.0±32.0）％和（-36.0±22.0）％]、△TLG[（76.0±90.0）％和（-15.0±44.0）％]存在差异（u=75.0和71.0,均P＜0.05）.病理分析发现放疗有效组肿瘤组织存在大量坏死灶及炎性细胞,有效组坏死率明显高于抵抗组[（63.0±15.0）％和（36.0±5.0）％;u=7.5,P＜0.05],有效组炎性细胞浸润率也高于抵抗组[（61.0±13.0）％和（43.0±15.0）％;u=18.5,P＜0.05].免疫组织化学分析发现,放疗有效组细胞增殖核抗原Ki67阳性率明显低于放疗抵抗组[（79.0±19.0）％和（130.0±45.0）％;u=81.5,P＜0.05].△TLG与肿瘤组织坏死率呈负相关（r=-0.57,P＜0.05）.结论 △TLG有望作为VX2肿瘤放疗效果的早期评估指标,用于指导肿瘤治疗方案的调整并在随访中发挥作用.

Objective To evaluate the predictive value of TLG in 18F-FDG PET/CT for early response to radiotherapy in VX2 tumor bearing rabbit models.Methods The rabbit models were established by transplanting VX2 tumor tissue into muscles of right legs.A total of 28 New Zealand rabbits were divided into control group （n =7） and radiation group （n =21） using random number table.1 8F-FDG PET studies were performed 1 d before and 7 d after radiotherapy （20 Gy）,and tumor glucose metabolic parameters （SUV,MTV,TLG,△SUV,△MTV,△TLG） were calculated.Based on histopathological analysis of the tumor specimens obtained after PET scan,the ratios of tumor cell necrosis,inflammatory cells infiltration and Ki67 positive staining were calculated.If a tumor doubled in volume or more than that on day 7,it was included into resistance group.Others were included into response group.The prognostic significance of △SUV,△MTV,△TLG was assessed by Mann-Whitney u test,the correlation between histopathological necrosis ratio and the change of TLG was analyzed by Pearson correlation analysis.Results Seven days after radiotherapy,there was no difference in △MTV value between the response group （n =7） and the resistance group （n=12）：（23.0±47.0）% vs （51.0±52.0）%; u=44.0,P〉0.05.However,there were significant differences in △SUV （（-36.0±22.0）% vs （10.0±32.0）%; u=75.0） and △TLG （（-15.0±44.0） % vs （76.0±90.0）%,u =71.0） values between the 2 groups （both P〈0.05）.Histopathological analysis confirmed that there were a large number of necrotic foci and inflammatory cells in the response group.Significant differences in necrosis rate and inflammatory cells infiltration were found between the response group and resistance group （（63.0±15.0）% vs （36.0±5.0）%,u=7.5; （61.0±13.0）% vs （43.0±15.0）%,u=18.5;both P〈0.05）,and the Ki67-positive rate significantly reduced （（79.0± 19.0）% vs （130.0±45.0）%,u=81.5,P〈0.05）.△TLG and tumor necrosis rate were correlated significantly （r=-0.57,P〈0.05）.Conclusion △TLG may have potential to predict early response to radiotherapy in VX2 tumor,and it could be helpful in tumor therapeutic planning and follow-up.