I. Medizinische Klinik und Poliklinik, Universitätsmedizin Mainz, Mainz, Germany.
Gastroenterology. 2010 Feb;138(2):435-46. doi: 10.1053/j.gastro.2009.10.032. Epub 2009 Oct 21.
BACKGROUND & AIMS: Epidermal growth factor receptor (EGFR) is a therapeutic target for colorectal cancer (CRC). However, technical challenges have limited in vivo imaging of EGFR in CRCs. Confocal laser endomicroscopy (CLE) enables accurate microscopic visualization of CRC in patients during endoscopy. We evaluated the ability to use CLE in vivo for instantaneous molecular imaging of EGFR in CRC models.
Tumors were grown in mice (n = 68) from human CRC cell lines that expressed high (SW480 cells) or low (SW620 cells) levels of EGFR. Tumors were visualized in vivo with a handheld CLE probe after injection of fluorescently labeled EGFR antibodies. EGFR-specific fluorescence was graded from 0 to 3+. Neoplastic and non-neoplastic specimens from human colorectal mucosa were examined. In vivo findings were correlated with histopathology, immunohistochemistry, and fluorescence microscopy analyses.
CLE analysis of cell cultures confirmed the different expression levels of EGFR between cell lines. In living animals, CLE differentiated EGFR expression levels between tumor cell limes (mean fluorescence, 1.92 +/- 0.22 [SW480] and 0.59 +/- 0.21 [SW620], P = .0004). CLE analysis of EGFR expression in human specimens allowed distinction of neoplastic from non-neoplastic tissues (mean fluorescence, 2.0 +/- 0.37 vs 0.25 +/- 0.16, respectively, P = .0035).
CLE can be used for in vivo, molecular analysis of CRC and to differentiate EGFR expression patterns in xenograft tumors and human tissue samples. Because CLE can be performed during endoscopy, in vivo molecular imaging might be used in diagnosis of CRC and to predict response to targeted therapies.
表皮生长因子受体（EGFR）是结直肠癌（CRC）的治疗靶点。然而，技术挑战限制了 CRC 中 EGFR 的体内成像。共聚焦激光内镜（CLE）使我们能够在结肠镜检查期间对患者的 CRC 进行准确的微观可视化。我们评估了在 CRC 模型中使用 CLE 进行 EGFR 瞬时分子成像的能力。
从表达高水平（SW480 细胞）或低水平（SW620 细胞）EGFR 的人 CRC 细胞系中在小鼠中生长肿瘤。在注射荧光标记的 EGFR 抗体后，使用手持式 CLE 探头对体内肿瘤进行可视化。EGFR 特异性荧光从 0 到 3+进行分级。检查人结直肠黏膜的肿瘤和非肿瘤标本。将体内发现与组织病理学、免疫组织化学和荧光显微镜分析相关联。
细胞培养物的 CLE 分析证实了细胞系之间 EGFR 的不同表达水平。在活体动物中，CLE 区分了肿瘤细胞系之间的 EGFR 表达水平（平均荧光强度，1.92 +/- 0.22 [SW480] 和 0.59 +/- 0.21 [SW620]，P =.0004）。对人类标本中 EGFR 表达的 CLE 分析允许区分肿瘤与非肿瘤组织（平均荧光强度分别为 2.0 +/- 0.37 和 0.25 +/- 0.16，P =.0035）。
CLE 可用于 CRC 的体内分子分析，并区分异种移植肿瘤和人类组织样本中的 EGFR 表达模式。因为 CLE 可以在结肠镜检查期间进行，所以体内分子成像可能用于 CRC 的诊断和预测对靶向治疗的反应。
