Positron emission tomography imaging and biodistribution of vascular endothelial growth factor with 64Cu-labeled bevacizumab in colorectal cancer xenografts
Positron emission tomography imaging and biodistribution of vascular endothelial growth factor with 64Cu-labeled bevacizumab in colorectal cancer xenografts
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DOI：
10.1111/j.1349-7006.2010.01763.x
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发表时间：
2011-01-01
期刊：
影响因子：
5.7
通讯作者：
Endo, Keigo
中科院分区：
文献类型：
--
作者：
Paudyal, Bishnuhari;Paudyal, Pramila;Endo, Keigo
血管内皮生长因子（VEGF）被认为是一种主要的血管生成因子，负责肿瘤血管的发展。本研究的目的是用64 Cu标记的抗VEGF抗体（贝伐单抗）非侵入性地对VEGF表达进行成像，并观察该表达是否与结直肠癌异种移植物中的肿瘤蓄积相关。贝伐珠单抗与双功能螯合剂1，4，7，10-四氮杂环十二烷-1，4，7，10-四乙酸（DOTA）偶联，并用64 Cu进行放射性标记。在注射64 Cu-DOTA-贝伐单抗后，对携带人结肠直肠癌（HT 29）异种移植物的小鼠进行体内生物分布研究和正电子发射断层扫描（PET）成像，其显示64 Cu-DOTA-贝伐单抗在肿瘤中明显积聚（在24、48和72小时分别为22.7 +/-1.0%ID/g、24 +/-0.2%ID/g、19.0 +/-2.5%ID/g）。64 Cu-DOTA-贝伐单抗的肿瘤蓄积与VEGF表达显著相关，如通过蛋白质印迹测量的（rho = 0.81，P = 0.004）。用未标记的贝伐单抗阻断血管内皮生长因子在48小时显著降低了64 Cu-DOTA-贝伐单抗的肿瘤积累（9.7 +/-1.2%ID/g，P < 0.001）。有趣的是，在48 h时，用过量倍贝伐单抗治疗的小鼠中VEGF的血液浓度显著高于未用贝伐单抗治疗的小鼠（25.5 +/-4.6%ID/g vs 6.5 +/-2.1%ID/g，P = 0.0016）。由于示踪剂的肝脏清除，肝脏摄取从24 h（17.2 +/-1.7% ID/g）降低至48 h（13.0 +/-4.2% ID/g）和72 h（10.6 +/-1.5% ID/g）。本研究成功显示64 Cu-DOTA-贝伐单抗作为潜在的PET示踪剂用于结肠直肠癌异种移植物中VEGF表达的非侵入性成像。（Cancer Sci 2011; 102：117-121）。
Vascular endothelial growth factor (VEGF) is considered to be a major angiogenic factor responsible for the development of tumor vasculature. The aim of this study was to image VEGF expression with 64Cu-labeled anti-VEGF antibody (bevacizumab) non-invasively, and to see whether or not the expression was correlated with tumor accumulation in colorectal cancer xenografts. Bevacizumab was conjugated with the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetraacetic acid (DOTA) and radiolabeled with 64Cu. In vivo biodistribution studies and positron emission tomography (PET) imaging were performed on mice bearing human colorectal cancer (HT29) xenografts after injection of 64Cu-DOTA-bevacizumab, which showed clear accumulation of 64Cu-DOTA-bevacizumab in the tumor (22.7 +/- 1.0 %ID/g, 24 +/- 0.2 %ID/g, 19.0 +/- 2.5 %ID/g at 24, 48 and 72 h, respectively). Tumor accumulation of 64Cu-DOTA-bevacizumab was significantly correlated with VEGF expression as measured by western blot (rho = 0.81, P = 0.004). Vascular endothelial growth factor blocking with unlabeled bevacizumab significantly reduced tumor accumulation of 64Cu-DOTA- bevacizumab (9.7 +/- 1.2 %ID/g, P < 0.001) at 48 h. Interestingly, the blood concentration of VEGF in the mice treated with excess fold of bevacizumab was significantly higher than those without at 48 h (25.5 +/- 4.6 %ID/g vs 6.5 +/- 2.1 %ID/g, P = 0.0016). Liver uptake decreased from 24 h (17.2 +/- 1.7 %ID/g) to 48 h (13.0 +/- 4.2 %ID/g) and 72 h (10.6 +/- 1.5 %ID/g) due to hepatic clearance of the tracer. The present study successfully showed 64Cu-DOTA-bevacizumab as a potential PET tracer for non-invasive imaging of VEGF expression in colorectal cancer xenografts. (Cancer Sci 2011; 102: 117-121).