Abstract
White-light surveillance colonoscopy is the standard of care for the detection and removal of premalignant lesions to prevent colorectal cancer, and the main screening recommendation following treatment for recurrence detection. However, it lacks sufficient diagnostic yield, exhibits unacceptable adenoma miss-rates and is not capable of revealing functional and morphological information of the detected lesions. Fluorescence molecular guidance in the near-infrared (NIR) is expected to have outstanding relevance regarding early lesion detection and heterogeneity characterization within and among lesions in these interventional procedures. Thereby, superficial and sub-surface tissue biomarkers can be optimally visualized due to a minimization of tissue attenuation and autofluorescence by comparison with the visible, which simultaneously enhance tissue penetration and assure minimal background. At present, this potential is challenged by the difficulty associated with the clinical propagation of disease-specific contrast agents and the absence of a commercially available endoscope that is capable of acquiring wide-field, NIR fluorescence at video-rates. We propose two alternative flexible endoscopic fluorescence imaging methods, each based on a CE certified commercial, clinical grade endoscope, and the employment of an approved monoclonal antibody labeled with a clinically applicable NIR fluorophore. Pre-clinical validation of these two strategies that aim at bridging NIR fluorescence molecular guidance to clinical translation is demonstrated in this study.
Highlights
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in the western world and is one of the most prevalent cancer types both in men and women [1]
The main unmet key aspects in surveillance colonoscopy, which is the current standard for the prevention and relapse screening of CRC, are early lesion detection and the identification of the tumor characteristics to determine the optimal treatment for the individual patients diagnosed with the disease
Fluorescence molecular guidance in NIR is expected to have outstanding relevance regarding early lesion detection and revealing functional and morphological information of the detected lesions, thereby improving the diagnostic yield of surveillance colonoscopy and identifying the optimal treatment for the diagnosed patient. These clinical potentialities are currently prevented by the regulatory difficulties in the clinical propagation of diseasespecific fluorescent agents and the lack of a commercially available flexible endoscope that is capable of acquiring simultaneous color and NIR fluorescence images at video-rates
Summary
Colorectal cancer (CRC) remains the second leading cause of cancer-related deaths in the western world and is one of the most prevalent cancer types both in men and women [1]. Along these lines, the main unmet key aspects in surveillance colonoscopy, which is the current standard for the prevention and relapse screening of CRC, are early lesion detection and the identification of the tumor characteristics to determine the optimal treatment for the individual patients diagnosed with the disease. Despite the wide clinical acceptance of white-light colonoscopy, its lack of sensitivity to sub-surface activity and its incapability to elucidate particular physiological and molecular disease features of the detected premalignant lesions result in substantial lesion miss-rates that can be as high as 55% in patients with an inherited predisposition to colon cancer, such as Lynch syndrome [5]
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