Vaselli Margherita, Gabriels Ruben Y, Schmidt Iris, Sterkenburg Andrea J, Kats-Ugurlu Gursah, Nagengast Wouter B, de Boer Johannes F
Department of Physics and Astronomy, LaserLab Amsterdam, Vrije Universiteit de Boelelaan 1081,, Amsterdam, The Netherlands.
Department of Gastroenterology and Hepatology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Biomed Opt Express. 2024 Sep 5;15(10):5706-5722. doi: 10.1364/BOE.537828. eCollection 2024 Oct 1.
Early detection of (pre)malignant esophageal lesions is critical to improve esophageal cancer morbidity and mortality rates. In patients with advanced esophageal adenocarcinoma (EAC) who undergo neoadjuvant chemoradiation therapy, the efficacy of therapy could be optimized and unnecessary surgery prevented by the reliable assessment of residual tumors after therapy. Optical coherence tomography (OCT) provides structural images at a (sub)-cellular level and has the potential to visualize morphological changes in tissue. However, OCT lacks molecular imaging contrast, a feature that enables the study of biological processes at a cellular level and can enhance esophageal cancer diagnostic accuracy. We combined OCT with near-infrared fluorescence molecular imaging using fluorescently labelled antibodies (immuno-OCT). The main goal of this proof of principle study is to investigate the feasibility of immuno-OCT for esophageal cancer imaging. We aim to assess whether the sensitivity of our immuno-OCT device is sufficient to detect the tracer uptake using an imaging dose (∼100 times smaller than a dose with therapeutic effects) of a targeted fluorescent agent. The feasibility of immuno-OCT was demonstrated on dysplastic lesions resected from Barrett's patients and on esophageal specimens resected from patients with advanced EAC, who were respectively topically and intravenously administrated with the tracer bevacizumab-800CW. The detection sensitivity of our system (0.3 nM) is sufficient to detect increased tracer uptake with micrometer resolution using an imaging dose of labelled antibodies. Moreover, the absence of layered structures that are typical of normal esophageal tissue observed in OCT images of dysplastic/malignant esophageal lesions may further aid their detection. Based on our preliminary results, immuno-OCT could improve the detection of dysplastic esophageal lesions.
早期发现食管（癌前）恶性病变对于提高食管癌的发病率和死亡率至关重要。在接受新辅助放化疗的晚期食管腺癌（EAC）患者中，通过可靠评估治疗后残留肿瘤，可以优化治疗效果并避免不必要的手术。光学相干断层扫描（OCT）可提供亚细胞水平的结构图像，有潜力可视化组织中的形态变化。然而，OCT缺乏分子成像对比度，而这一特性能够在细胞水平研究生物过程并提高食管癌诊断准确性。我们将OCT与使用荧光标记抗体的近红外荧光分子成像相结合（免疫OCT）。这项原理验证研究的主要目标是探究免疫OCT用于食管癌成像的可行性。我们旨在评估我们的免疫OCT设备的灵敏度是否足以使用靶向荧光剂的成像剂量（比具有治疗效果的剂量小约100倍）检测示踪剂摄取。免疫OCT的可行性在分别从巴雷特食管患者切除的发育异常病变以及从晚期EAC患者切除的食管标本上得到了证实，这些患者分别经局部和静脉注射示踪剂贝伐单抗 - 800CW。我们系统的检测灵敏度（0.3 nM）足以使用标记抗体的成像剂量以微米分辨率检测示踪剂摄取增加。此外，在发育异常/恶性食管病变的OCT图像中观察到的正常食管组织典型分层结构的缺失可能进一步有助于其检测。基于我们的初步结果，免疫OCT可以改善发育异常食管病变的检测。
