Marcazzan Sabrina, Braz Carvalho Marcos J, Konrad Matthias, Strangmann Julia, Tenditnaya Anna, Baumeister Theresa, Schmid Roland M, Wester Hans-Jürgen, Ntziachristos Vasilis, Gorpas Dimitris, Wang Timothy C, Schottelius Margret, Quante Michael
II Medizinische Klinik, Klinikum rechts der isar, Technische Universität München, Munich, Germany.
Chair of Biological Imaging, School of Medicine, Technische Universität München, Munich, Germany.
EJNMMI Res. 2022 Jan 10;12(1):2. doi: 10.1186/s13550-021-00875-7.
Near-infrared (NIR) fluorescence imaging has been emerging as a promising strategy to overcome the high number of early esophageal adenocarcinomas missed by white light endoscopy and random biopsy collection. We performed a preclinical assessment of fluorescence imaging and endoscopy using a novel CXCR4-targeted fluorescent peptide ligand in the L2-IL1B mouse model of Barrett's esophagus.
Six L2-IL1B mice with advanced stage of disease (12-16 months old) were injected with the CXCR4-targeted, Sulfo-Cy5-labeled peptide (MK007), and ex vivo wide-field imaging of the whole stomach was performed 4 h after injection. Before ex vivo imaging, fluorescence endoscopy was performed in three L2-IL1B mice (12-14 months old) by a novel imaging system with two L2-IL1B mice used as negative controls.
Ex vivo imaging and endoscopy in L2-IL1B mice showed that the CXCR4-targeted MK007 accumulated mostly in the dysplastic lesions with a mean target-to-background ratio > 2. The detection of the Sulfo-Cy5 signal in dysplastic lesions and its co-localization with CXCR4 stained cells by confocal microscopy further confirmed the imaging results.
This preliminary preclinical study shows that CXCR4-targeted fluorescence endoscopy using MK007 can detect dysplastic lesions in a mouse model of Barrett's esophagus. Further investigations are needed to assess its use in the clinical setting.
近红外（NIR）荧光成像已成为一种有前景的策略，以克服白光内镜检查和随机活检所遗漏的大量早期食管腺癌。我们在巴雷特食管的L2-IL1B小鼠模型中，使用一种新型的靶向CXCR4的荧光肽配体，对荧光成像和内镜检查进行了临床前评估。
给6只处于疾病晚期（12 - 16个月大）的L2-IL1B小鼠注射靶向CXCR4的磺基-Cy5标记肽（MK007），注射后4小时对整个胃进行离体宽视野成像。在进行离体成像之前，通过一种新型成像系统，对3只L2-IL1B小鼠（12 - 14个月大）进行荧光内镜检查，另外2只L2-IL1B小鼠用作阴性对照。
L2-IL1B小鼠的离体成像和内镜检查显示，靶向CXCR4的MK007主要聚集在发育异常的病变中，平均靶标与背景比>2。通过共聚焦显微镜在发育异常病变中检测磺基-Cy5信号及其与CXCR4染色细胞的共定位，进一步证实了成像结果。
这项初步的临床前研究表明，使用MK007的靶向CXCR4荧光内镜检查可在巴雷特食管小鼠模型中检测到发育异常病变。需要进一步研究以评估其在临床环境中的应用。
