BACKGROUND Near-infrared fluorescence (NIRF) imaging combined with enzyme-activatable NIRF probes has yielded promising results in cancer detection. OBJECTIVE To test whether 3-dimensional (3-D) noninvasive in vivo NIRF imaging can detect effects of epidermal growth factor receptor (EGFR) inhibitor on both polypoid and flat tumor load in azoxymethane (AOM)-induced colon tumors or tumors in ApcMin/+ mice. METHODS The AOM-injected KK-HIJ mice received EGFR inhibitor diet or chow diet. These and ApcMin/+ mice were given cathepsin-activatable probes (ProSense 680) before imaging. In vivo imaging was performed using quantitative tomographic NIRF imaging. Ex vivo imaging and histologic examination were performed. Dual imaging by micro computed tomography (CT) and 3D NIRF imaging was used to verify tumor location. RESULTS Tumor load reduction by EGFR inhibition was detected ex vivo using cathepsin B probes. In vivo imaging revealed intense activation of probes only in large tumors. Dual imaging with microCT and 3D NIRF imaging improved tumor detection in vivo. CONCLUSIONS The 3-D NIRF imaging with ProSense 680 can detect and quantify drug effects on colon tumors ex vivo. The NIRF imaging with ProSense 680 probe has limitations as a valid nonendoscopic method for intestinal tumor detection. Combing with other imaging modalities will improve the specificity and sensitivity of intestinal tumor detection in vivo.

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使用可激活的近红外荧光探针对表皮生长因子受体抑制结肠肿瘤发生的体内和体外非侵入性成像。

背景技术近红外荧光（NIRF）成像与酶激活的NIRF探针相结合已在癌症检测中产生了令人鼓舞的结果。目的测试3维（3-D）体内无创NIRF成像能否检测表皮生长因子受体（EGFR）抑制剂对由乙氧基甲烷（AOM）诱导的结肠肿瘤或ApcMin / +老鼠。方法注射AOM的KK-HIJ小鼠接受EGFR抑制剂饮食或低脂饮食。在成像之前，对这些和ApcMin / +小鼠给予了组织蛋白酶激活探针（ProSense 680）。使用定量断层摄影NIRF成像进行体内成像。进行了离体成像和组织学检查。通过微计算机断层扫描（CT）和3D NIRF成像进行双重成像来验证肿瘤的位置。结果使用组织蛋白酶B探针离体检测到EGFR抑制导致的肿瘤负荷降低。体内成像显示仅在大肿瘤中才强烈激活探针。使用microCT和3D NIRF成像进行双重成像可改善体内肿瘤检测。结论用ProSense 680进行的3-D NIRF成像可以离体检测和量化药物对结肠肿瘤的作用。使用ProSense 680探针的NIRF成像作为一种有效的非内窥镜检查肠肿瘤的方法存在局限性。与其他成像方式相结合，将提高体内肠道肿瘤检测的特异性和敏感性。结论用ProSense 680进行的3-D NIRF成像可以离体检测和量化对结肠肿瘤的药物作用。使用ProSense 680探针的NIRF成像作为一种有效的非内窥镜检查肠肿瘤的方法存在局限性。与其他成像方式相结合，将提高体内肠道肿瘤检测的特异性和敏感性。结论用ProSense 680进行的3-D NIRF成像可以离体检测和量化对结肠肿瘤的药物作用。使用ProSense 680探针的NIRF成像作为一种有效的非内窥镜检查肠肿瘤的方法存在局限性。与其他成像方式相结合，将提高体内肠道肿瘤检测的特异性和敏感性。