Gabriëls Ruben Y, van Heijst Lisanne E, Hooghiemstra Wouter T R, van der Waaij Anne M, Kats-Ugurlu Gursah, Karrenbeld Arend, Robinson Dominic J, Tenditnaya Anna, Ntziachristos Vasilis, Gorpas Dimitris, Nagengast Wouter B
Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
J Nucl Med. 2023 May;64(5):803-808. doi: 10.2967/jnumed.122.264656. Epub 2023 Jan 5.
Esophageal adenocarcinoma causes 6% of cancer-related deaths worldwide. Near-infrared fluorescence molecular endoscopy (NIR-FME) uses a tracer that targets overexpressed proteins. In this study, we aimed to investigate the feasibility of an epidermal growth factor receptor (EGFR)-targeted tracer, cetuximab-800CW, to improve detection of early-stage esophageal adenocarcinoma. We validated EGFR expression in 73 esophageal tissue sections. Subsequently, we topically administered cetuximab-800CW and performed high-definition white-light endoscopy (HD-WLE), narrow-band imaging, and NIR-FME in 15 patients with Barrett esophagus (BE). Intrinsic fluorescence values were quantified using multidiameter single-fiber reflectance and single-fiber fluorescence spectroscopy. Back-table imaging, histopathologic examination, and EGFR immunohistochemistry on biopsy samples collected during NIR-FME procedures were performed and compared with in vivo imaging results. Immunohistochemical preanalysis showed high EGFR expression in 67% of dysplastic tissue sections. NIR-FME visualized all 12 HD-WLE-visible lesions and 5 HD-WLE-invisible dysplastic lesions, with increased fluorescence signal in visible dysplastic BE lesions compared with nondysplastic BE as shown by multidiameter single-fiber reflectance/single-fiber fluorescence, reflecting a target-to-background ratio of 1.5. Invisible dysplastic lesions also showed increased fluorescence, with a target-to-background ratio of 1.67. Immunohistochemistry analysis showed EGFR overexpression in 16 of 17 (94%) dysplastic BE lesions, which all showed fluorescence signal. This study has shown that NIR-FME using cetuximab-800CW can improve detection of dysplastic lesions missed by HD-WLE and narrow-band imaging.
食管腺癌导致全球6%的癌症相关死亡。近红外荧光分子内镜检查（NIR-FME）使用一种针对过表达蛋白的示踪剂。在本研究中，我们旨在探讨表皮生长因子受体（EGFR）靶向示踪剂西妥昔单抗-800CW改善早期食管腺癌检测的可行性。我们在73个食管组织切片中验证了EGFR表达。随后，我们对15例巴雷特食管（BE）患者局部给予西妥昔单抗-800CW，并进行了高清白光内镜检查（HD-WLE）、窄带成像和NIR-FME。使用多直径单纤维反射率和单纤维荧光光谱法定量内在荧光值。对NIR-FME过程中收集的活检样本进行了后台成像、组织病理学检查和EGFR免疫组织化学分析，并与体内成像结果进行了比较。免疫组织化学预分析显示，67%的发育异常组织切片中EGFR高表达。NIR-FME可视化了所有12个HD-WLE可见病变和5个HD-WLE不可见的发育异常病变，如多直径单纤维反射率/单纤维荧光所示，可见发育异常的BE病变中的荧光信号比非发育异常的BE增加，反映出靶标与背景的比率为1.5。不可见的发育异常病变也显示荧光增加，靶标与背景的比率为1.67。免疫组织化学分析显示，17个发育异常的BE病变中有16个（94%）EGFR过表达，所有病变均显示荧光信号。这项研究表明，使用西妥昔单抗-800CW的NIR-FME可以改善对HD-WLE和窄带成像遗漏的发育异常病变的检测。
