Reproducibility study of [18F]FPP(RGD)2 uptake in murine models of human tumor xenografts
Reproducibility study of [18F]FPP(RGD)2 uptake in murine models of human tumor xenografts
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DOI：
10.1007/s00259-010-1672-1
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发表时间：
2011-04-01
影响因子：
9.1
通讯作者：
Cheng, Zhen
中科院分区：
文献类型：
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作者：
Chang, Edwin;Liu, Shuangdong;Cheng, Zhen
在临床前和临床研究中，F-18标记的聚乙二醇化精氨酸-甘氨酸-天冬氨酸（RGD）二聚体{[F-18]FPP（RGD）（2）}已用于肿瘤α（v）β（3）整联蛋白水平成像。系列正电子发射断层扫描（PET）研究可能有助于监测抗血管生成治疗反应或药物筛选;然而，尚未确定该PET探头的系列扫描的再现性。本研究的目的是使用小动物PET确定整联蛋白α（v）β（3）靶向PET探针[F-18]FPP（RGD）（2，）的再现性。将人HCT 116结肠癌异种移植物植入裸鼠（n = 12）的乳房和肩胛区，并生长至平均直径5-15 mm约2.5周。经尾静脉给予[F-18]FPP（RGD）（2）（1.9-3.8 MBq，50-100 μ Ci）后约1小时，在小动物PET扫描仪上进行3分钟采集。在重新注射探针后约6小时进行第二次小动物PET扫描，以评估重现性。通过在肿瘤异种移植物活性周围绘制感兴趣的椭圆体区域（ROI）来分析图像。根据ROI中的平均或最大活性计算每克注射剂量百分比（%ID/g）值。计算同一天研究之间%ID/g值的变异系数和差异，以确定重现性。同一天间隔6小时进行的[F-18]FPP（RGD）（2）小动物PET扫描之间%ID平均值/g和%ID最大值/g值的变异系数（平均值+/- SD）分别为11.1 +/- 7.6%和10.4 +/-9.3%。扫描之间%ID平均值/g和%ID最大值/g值的相应差异为-0.025 +/- 0.067和-0.039 +/- 0.426。免疫荧光研究揭示了α（nu）β（3）整合素在肿瘤和肿瘤血管中的表达程度与示踪剂摄取水平之间的直接关系。小鼠体重、注射剂量和禁食状态对扫描的变异性没有贡献;然而，一致的扫描参数是确保准确研究所必需的，特别是注意肿瘤体积，以及使注射后成像时间和ROI大小一致。ROI位置的再分析显示%IDmean/g的变异性为6.6 +/- 3.9%，%IDmax/g的变异性为0.28 +/- 0.12%。[F-18]FPP（RGD）（2）小动物PET小鼠肿瘤异种移植研究具有重现性，变异性相对较低。
An F-18-labeled PEGylated arginine-glycine-aspartic acid (RGD) dimer {[F-18]FPP(RGD)(2)} has been used to image tumor alpha(v)beta(3) integrin levels in preclinical and clinical studies. Serial positron emission tomography (PET) studies may be useful for monitoring antiangiogenic therapy response or for drug screening; however, the reproducibility of serial scans has not been determined for this PET probe. The purpose of this study was to determine the reproducibility of the integrin alpha(v)beta(3)-targeted PET probe, [F-18]FPP(RGD)(2,) using small animal PET.Human HCT116 colon cancer xenografts were implanted into nude mice (n = 12) in the breast and scapular region and grown to mean diameters of 5-15 mm for approximately 2.5 weeks. A 3-min acquisition was performed on a small animal PET scanner approximately 1 h after administration of [F-18]FPP(RGD)(2) (1.9-3.8 MBq, 50-100 mu Ci) via the tail vein. A second small animal PET scan was performed approximately 6 h later after reinjection of the probe to assess for reproducibility. Images were analyzed by drawing an ellipsoidal region of interest (ROI) around the tumor xenograft activity. Percentage injected dose per gram (%ID/g) values were calculated from the mean or maximum activity in the ROIs. Coefficients of variation and differences in %ID/g values between studies from the same day were calculated to determine the reproducibility.The coefficient of variation (mean +/- SD) for %IDmean/g and %IDmax/g values between [F-18]FPP(RGD)(2) small animal PET scans performed 6 h apart on the same day were 11.1 +/- 7.6% and 10.4 +/- 9.3%, respectively. The corresponding differences in %IDmean/g and %IDmax/g values between scans were -0.025 +/- 0.067 and -0.039 +/- 0.426. Immunofluorescence studies revealed a direct relationship between extent of alpha(nu)beta(3) integrin expression in tumors and tumor vasculature with level of tracer uptake. Mouse body weight, injected dose, and fasting state did not contribute to the variability of the scans; however, consistent scanning parameters were necessary to ensure accurate studies, in particular, noting tumor volume, as well as making uniform: the time of imaging after injection and the ROI size. Reanalysis of ROI placement displayed variability for %IDmean/g of 6.6 +/- 3.9% and 0.28 +/- 0.12% for %IDmax/g.[F-18]FPP(RGD)(2) small animal PET mouse tumor xenograft studies are reproducible with relatively low variability.