Thayer School of Engineering, Dartmouth College, Hanover, NH 03755, USA.
Acad Radiol. 2010 Mar;17(3):271-6. doi: 10.1016/j.acra.2009.11.001.
This report demonstrates the diagnostic potential of magnetic resonance imaging (MRI)-coupled fluorescence molecular tomography (FMT) to determine epidermal growth factor receptor (EGFR) status in brain cancer.
Two orthotopic glioma xenograft models were used in this study: one represented high EGFR expression and the other low expression. Nude mice were inoculated with cells from either one of the tumor lines or were used in a sham surgery control group. Animals were imaged using a unique MRI-FMT scanner 48 hours after intravenous injection of a near-infrared fluorophore bound to epidermal growth factor (EGF) ligand. Coronal images of fluorescence activity of the injected dye in the mouse brain were recovered using the MRI images as anatomical templates.
In vivo images of fluorescence activity showed significant differences between animal populations, an observation confirmed by receiver operating characteristic analysis that revealed 100% sensitivity and specificity between animal groups implanted with EGFR((+)) and EGFR((-)) tumor lines. Similar performance was observed between EGFR((+)) and sham surgery control animals.
This preclinical study suggests that MRI-FMT with fluorescent EGF provides excellent discrimination between tumors based on EGFR status. Reliable quantification of receptor status using minimally invasive techniques would be an important innovation for investigating new and existing cancer treatments that target these cellular mechanisms in research animals, and may be applied to identify receptor amplification in human brain cancer patients. This study represents the first systematic multianimal validation of receptor-specific imaging using MRI-guided fluorescence tomography.
本报告展示了磁共振成像（MRI）-荧光分子断层扫描（FMT）结合在确定脑癌表皮生长因子受体（EGFR）状态方面的诊断潜力。
本研究使用了两种原位脑肿瘤异种移植模型：一种代表高 EGFR 表达，另一种代表低表达。将来自肿瘤系的细胞接种到裸鼠中，或用于假手术对照组。在静脉注射与表皮生长因子（EGF）配体结合的近红外荧光染料 48 小时后，使用独特的 MRI-FMT 扫描仪对动物进行成像。使用 MRI 图像作为解剖模板，恢复注射染料在小鼠脑中的荧光活性的冠状图像。
荧光活性的体内图像显示动物群体之间存在显著差异，这一观察结果通过接受者操作特征分析得到了证实，该分析显示 EGFR((+)）和 EGFR((-））肿瘤系植入动物组之间具有 100％的敏感性和特异性。EGFR((+)）和假手术对照组动物之间也观察到了类似的表现。
这项临床前研究表明，使用荧光 EGF 的 MRI-FMT 可根据 EGFR 状态出色地区分肿瘤。使用微创技术可靠地定量受体状态将是研究动物中针对这些细胞机制的新的和现有的癌症治疗方法的重要创新，并且可能应用于识别人类脑癌患者的受体扩增。这项研究代表了首次使用 MRI 引导的荧光断层扫描对受体特异性成像进行的系统多动物验证。
