microSPECT/CT显像定量评价肿瘤^(99m)Tc-3P4-RGD_2摄取及整合素α_Vβ_3表达水平的实验研究

Quantitive analysis of ^(99m)Tc-3P4-RGD_2 uptake and tumor integrin α_Vβ_3 expression in glioma bearing nude mice with microSPECT/CT imaging

目的:探讨99mTc-HYNIC-PEG4-E[PEG4-c(RGDfk)]2(简称99mTc-3P4-RGD2)microSPECT/CT显像定量肿瘤放射性摄取及整合素αvβ3表达水平的可行性研究。方法:对不同99mTc样品进行microSPECT/CT显像,评价样品体积、活度对放射性计数的影响;对荷脑胶质瘤裸鼠行99mTc-3P4-RGD2microSPECT/CT显像,对比基于CT、SPECT及融合图像测定的肿瘤体积与肿瘤实际体积一致性,并评价肿瘤整合素αvβ3表达水平,由病理证实。结果:99mTc样品microSPECT/CT显像放射性计数与其放射性活度呈直线相关(R2=0.999 7),Bland-Altman一致性分析显示,基于microSPECT/CT测定的肿瘤体积与肿瘤实际体积差异(%)为-2.48±8.17,显著低于microCT(15.04±79.53,t=5.60,P=0.005)和microSPECT(17.04±36.27,t=7.17,P=0.002);microSPECT/CT显像肿瘤99mTc-3P-RGD2摄取与整合素αvβ3表达呈正相关。结论:microSPECT/CT显像可定量99mTc放射性活度和成活肿瘤组织体积,有效评估整合素αvβ3受体表达,为肿瘤整合素受体靶向治疗患者筛选及药物剂量个体化提供影像学数据。

Objective：To investigate the possibility of quantitive analysis of^99mTc-HYNIC-PEG4-E [PEG4-c（RGDfk）]2（^99mTc-3P4-RGD2） uptake and tumor integrin αvβ3expression in glioma bearing nude mice with microSPECT / CT imaging.Methods：microSPECT / CT imaging of^99mTc samples with different volume and radioactivity was carried out to assess the influence on radiocounting based upon volume and activity.^99mTc-3P4-RGD2MicroSPECT / CT imaging was also carried out to glioma bearing nude mice.Tumor volume was determined in vivo by caliper,microCT,microSPECT and microSPECT / CT.The consistency between determined volume and actual volume was analyzed by Bland-Altman plots.Tumor uptake of^99mTc-3P4-RGD2was quantified to estimate glioma expression level of integrin αvβ3and confirmed by immunohistochemistry examination.Results：Linear relationship with R2being 0.999 7 was found between the radioactivity counts from the SPECT / CT fusion images and those from γ-counter.Bias of microSPECT / CT measurements（%） compared with the reference ones was（-2.48 ± 8.17）,less than that of microCT（15.04 ± 79.53,t =5.60,P = 0.005）,microSPECT（17.04 ± 36.27,t = 7.17,P = 0.002）,respectively.MicroSPECT / CT can reflect vial and necrotic tumor volume and tumor uptake of^99mTc-3P-RGD2was positively correlated with integrin αvβ3expression with R^2being 0.95.Conclusion：MicroSPECT / CT imaging,which is more accurate in evaluating via tumor volume and integrin αvβ3expression level,is of potential value for patients screening for integrin αvβ3receptor targeted therapy and dose individualization.