Early diagnosis of colorectal cancer using Cerenkov luminescence endoscopy: a pilot trial involving humans for the first time.

Rationale: Current gastrointestinal endoscopy mainly depends on morphological changes for lesion diagnosis, thus often failing to detect early colorectal cancers (CRCs) with subtle morphological alterations. Optical molecular imaging via endoscopy may provide a unique means to identify early CRCs that precede the morphological changes observed via conventional endoscopy. In addition, optical imaging methods are utilized for intraoperative navigation when imaging tumors. However, the primary challenge in applying optical molecular imaging clinically is the restricted kinds of clinically endorsed targeted probes. Cerenkov luminescence (CL) can be observed with almost all clinically validated radiotracers. Therefore, Cerenkov luminescence imaging (CLI) does not require the development of new probes and can directly utilize clinically validated radiotracers. This study aimed to use Cerenkov luminescence endoscopy (CLE) for diagnosing early CRC effectively. Methods: In a prospective observational study, we use a self-produced CLE to diagnose colorectal lesions (mainly CRC). The CL images of the lesions were recorded and analyzed in comparison with PET/CT scans and histopathology. Results: A total of 20 colorectal lesions from 15 patients were included in the study. The agreement between CLE and PET/CT in diagnosing early CRC (stage Ⅰ CRC and advanced adenoma) was 100%. The level of agreement of CLE images with histopathology was 88.9% acceptable to high for early CRC. Compared with that of colorectal hyperplastic polyps, the signal-to-background ratio of CLE from early CRCs was significantly greater (1.33 ± 0.17 vs 0.99 ± 0.03, P < 0.001). In phantoms, tumor-bearing nude mice, and rectal pseudotumor model dogs, CLE detected CL at the corresponding lesion locations. Conclusions: This study demonstrated for the first time that CLE could utilize Cerenkov luminescence molecular imaging to diagnose early CRCs, overcoming the limitations of current endoscopic diagnosis based on morphological changes. (ClinicalTrials.gov, NCT05575765).