Use of 64Cu-labeled Fibronectin Domain with EGFR-Overexpressing Tumor Xenograft: Molecular Imaging
Use of 64Cu-labeled Fibronectin Domain with EGFR-Overexpressing Tumor Xenograft: Molecular Imaging
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DOI：
10.1148/radiol.12111504
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发表时间：
2012-04-01
期刊：
影响因子：
19.7
通讯作者：
Gambhir, Sanjiv S.
中科院分区：
文献类型：
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作者：
Hackel, Benjamin J.;Kimura, Richard H.;Gambhir, Sanjiv S.
目的：评估工程化表皮生长因子受体（EGFR）结合纤连蛋白结构域作为正电子发射断层扫描（PET）探针用于异种移植小鼠模型中EGFR分子成像的能力。材料和方法：EGFR结合纤连蛋白结构域（结合时纤连蛋白缩写为Fn）用铜64（Cu-64）（8 MBq/nmol）进行位点特异性标记。在具有不同EGFR表达的细胞培养物中测试铜64-Fn结合。在体外测量了人和小鼠血清中的稳定性。动物实验由斯坦福大学机构动物护理和使用委员会批准。铜64-Fn（约2 MBq）用于携带EGFR过表达异种移植肿瘤（直径约5-10 mm）的小鼠（n = 5）的PET。断层扫描的结果进行了比较与离体γ计数的解剖组织。统计分析进行了t检验和调整的多重comparation.Results：铜64-Fn表现出EGFR依赖性结合培养中的多个细胞系。示踪剂在37 ℃下在人和小鼠血清中稳定24小时。示踪剂显示出良好的肿瘤定位（1小时时3.4%注射剂量[ ID]/g +/- 1.0 [标准差]）、保留（24小时时2.7% ID/g +/- 0.6）和特异性（1小时时8.6 +/- 3.0肿瘤-肌肉比，8.9 +/- 4.7肿瘤-血液比）。特异性靶向通过低表达MDA-MB-435肿瘤的低定位得到验证（1小时时0.7%ID/g +/- 0.8，P = 0.018）;进一步证明了特异性，因为非结合对照纤连蛋白对EGFR过表达异种移植物的定位较低结论：工程化纤连蛋白结构域的稳定性、低背景和靶向特异性肿瘤摄取和保留使其成为有希望的EGFR分子显像剂。更广泛地说，它验证了纤连蛋白结构域作为一个潜在的支架，产生各种分子成像剂。(C)RSNA，2012年
Purpose: To assess the ability of an engineered epidermal growth factor receptor (EGFR)-binding fibronectin domain to serve as a positron emission tomographic (PET) probe for molecular imaging of EGFR in a xenograft mouse model.Materials and Methods: An EGFR-binding fibronectin domain (fibronectin abbreviated to Fn when bound) was site-specifically labeled with copper 64 (Cu-64) (8 MBq/nmol). Copper 64-Fn binding was tested in cell cultures with varying EGFR expression. Stability in human and mouse serum was measured in vitro. Animal experiments were approved by the Stanford University Institutional Animal Care and Use Committee. Copper 64-Fn (approximately 2 MBq) was used for PET in mice (n = 5) bearing EGFR-overexpressing xenografted tumors (approximately 5-10 mm in diameter). Results of tomography were compared with those of ex vivo gamma counting of dissected tissues. Statistical analysis was performed with t tests and adjustment for multiple comparisons.Results: Copper 64-Fn exhibited EGFR-dependent binding to multiple cell lines in culture. The tracer was stable for 24 hours in human and mouse serum at 37 degrees C. The tracer exhibited good tumor localization (3.4% injected dose [ ID]/g +/- 1.0 [standard deviation] at 1 hour), retention (2.7% ID/g +/- 0.6 at 24 hours), and specificity (8.6 +/- 3.0 tumor-to-muscle ratio, 8.9 +/- 4.7 tumor-to-blood ratio at 1 hour). Specific targeting was verified with low localization to low-expressing MDA-MB-435 tumors (0.7% ID/g +/- 0.8 at 1 hour, P = .018); specificity was further demonstrated, as a nonbinding control fibronectin had low localization to EGFR-overexpressing xenografts (0.8% ID/g +/- 0.2 at 1 hour, P = .013).Conclusion: The stability, low background, and target-specific tumor uptake and retention of the engineered fibronectin domain make it a promising EGFR molecular imaging agent. More broadly, it validates the fibronectin domain as a potential scaffold for a generation of various molecular imaging agents. (C) RSNA, 2012