Abstract
Screening colonoscopy is crucial in reducing the mortality of colorectal cancer. However, detecting adenomas against the backdrop of an inflamed mucosa (e.g. in ulcerative colitis) remains exceedingly difficult. Therefore, we aimed to improve neoplastic lesion detection by employing a fluorescence-based endoscopic approach. We used the well-established murine AOM/DSS model to induce inflammation-driven carcinogenesis in the colon. In our diagnostic approach, we evaluated Chlorin e6 polyvinylpyrrolidone (Ce6-PVP)-based fluorescence endoscopy in comparison to standard white-light endoscopy. A specialized pathologist then analyzed the histology of the detected lesions. Complementary in vitro studies were performed using human cell lines and a murine organoid system. Ce6-PVP-based fluorescence endoscopy had an improved detection rate of 100% (8/8) in detecting high-grade dysplasias and carcinomas over white-light detection alone with 75% (6/8). Trade-off for this superior detection rate was an increased rate of false positive lesions with an increase in the false discovery rate from 45% for white-light endoscopy to 81% for fluorescence endoscopy. We demonstrate in a proof-of-concept study that Ce6-PVP-based fluorescence endoscopy is a highly sensitive red flag technology to identify biopsy-worthy lesions in the colon.
Highlights
Achieving high adenoma detection rates during screening colonoscopy remains a formidable challenge as small or flat lesions are difficult to detect[1,2,3]
We developed a fluorescence endoscopy approach employing the established substance Chlorin e6-polyvinylpyrrolidone (Ce6-PVP), which significantly improves on the existing specificity for malignant tissue displayed by Ce6 or other derivatives such as Ce6-DMSO7, as a diagnostic fluorophore
We found that colon tumor organoids emitted a reliably strong Ce6-PVP signal suitable for detection
Summary
Achieving high adenoma detection rates during screening colonoscopy remains a formidable challenge as small or flat lesions are difficult to detect[1,2,3]. Conflicting data on the best approach for surveillance strategies necessitate further research into emerging technologies such as fluorescence endoscopy To address this challenge, we developed a fluorescence endoscopy approach employing the established substance Chlorin e6-polyvinylpyrrolidone (Ce6-PVP), which significantly improves on the existing specificity for malignant tissue displayed by Ce6 or other derivatives such as Ce6-DMSO7, as a diagnostic fluorophore. The chemical modification of coupling Chlorin e6 to a polyvinylpyrrolidone (PVP) polymer in a mass ratio of 1:1 yields the high molecular weight compound Ce6-PVP (12,000 g/mol), which is commercially available as “Photolon” (Belmedpreparaty, Belarus) In this context, reduced aggregate formation in aqueous solutions[8] and increased cellular uptake over the plasma m embrane[9] compared to Ce6 are relevant advantages of Ce6-PVP. Previous studies have so far shown promising results regarding the general use of Ce6-PVP in diagnostic fluorescence imaging in vivo using xenograft models of bladder tumors[10] or nasopharynx carcinomas[11]
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