Molecular Fluorescence Endoscopy:clinical development and validation within the lower gastrointestinal tract

Molecular Fluorescence Imaging is a new and evolving imaging technique. It uses exogenous fluorescent tracers that bind to specific proteins, thereby fluorescently highlighting the tissue of interest as a red-flag for the clinician. White-light endoscopy is the current gold standard for colorectal adenoma and cancer screening, where gastroenterologist evaluate aberrant tissue based on morphological aspects and architectural changes only. As adenoma miss rates in colonoscopy are unacceptably high, especially in high-risk populations, we describe in this thesis a clinical dose-escalation study towards the use of Molecular Fluorescence Endoscopy for colorectal adenoma detection. This technique showed to have the potential to improve the identification of colorectal adenomas. In the second part of this thesis, the added value of a restaging CT scan after neoadjuvant chemoradiotherapy is shown for patients with locally advanced rectal cancer, as it may detect newly developed metastases. In a clinical study, the potential of Molecular Fluorescence Endoscopy as tool to aid clinical response assessment is shown, in patients with locally advanced rectal cancer. When this technique is performed after neoadjuvant chemoradiotherapy, it can help identifying the presence of residual tumor and has potential to predict pathological compete response (pCR) and in this way help selecting patients suitable for organ-preserving strategies. Additionally, we show in a proof-of-concept study that molecular fluorescence imaging performed peri-operative can help the surgeon evaluating the circumferential resection margin at the surgical theatre, preventing under- and overtreatment of patients in the future