Topical application of Chlorin e6-PVP (Ce6-PVP) for improved endoscopic detection of neoplastic lesions in a murine colitis-associated cancer model

Author:

Ganzleben Ingo,Hohmann Martin,Grünberg Alexander,Gonzales-Menezes Jean,Vieth Michael,Liebing Eva,Günther Claudia,Thonn Veronika,Beß Daniel,Becker Christoph,Schmidt Michael,Neurath Markus F.,Waldner Maximilian J.

Abstract

AbstractScreening 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.

Funder

Interdisciplinary Center for Clinical Research (IZKF) Erlangen

Erlangen Graduate School of Advanced Optical Technologies

Deutsche Forschungsgemeinschaft

Publisher

Springer Science and Business Media LLC

Subject

Multidisciplinary

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