Abstract IA10: Targeted imaging of the serrated pathway for early detection of colorectal cancer

Abstract

Abstract Background and Significance: Colorectal cancer (CRC) is a leading cause of cancer-related mortality with ~1.4 million new cases diagnosed globally and ~690,000 annual deaths. The serrated pathway is a primary cause of CRC in the proximal colon. Sessile serrated adenomas (SSA) have flat and subtle features that are difficult to detect with conventional white light colonoscopy. Aims: We aim to identify a peptide imaging agent that binds specifically to SSA to improve visualization of pre-malignant lesions in the proximal colon. Methods: We used phage display technology with subtractive biopanning against cells with a V600E point mutation in BRAF. We performed a first-in-humans clinical study by topically administering this FITC-labeled peptide in the proximal colon of n = 38 human subjects, and performed in vivo imaging using a wide-field endoscope that is sensitive to fluorescence. Results: We identified the peptide sequence KCCFPAQ, and measured an apparent dissociation constant of kd = 72 nM and an apparent association time constant of kd = 0.174 min-1 (5.76 min). On in vivo fluorescence images, we measured a 2.43-fold greater target-to-background ratio for SSA than for normal colonic mucosa, and could distinguish SSA with 89% sensitivity and 92% specificity. We found 84% sensitivity and 91% specificity for discriminating SSA from traditional adenomas. No toxicity was attributed to the peptide in either animal or patient studies. On ex vivo images, we found the mean fluorescence intensity for SSA to be significantly greater than that for hyperplastic polyps. Conclusions: We have identified a fluorescently-labeled peptide that is safe for clinical use, and is specific for detecting SSAs in the proximal colon with wide-field imaging. This targeted imaging methodology may be useful for early detection of pre-malignant serrated lesions on routine colonoscopy. Citation Format: Thomas D. Wang. Targeted imaging of the serrated pathway for early detection of colorectal cancer. [abstract]. In: Proceedings of the AACR Special Conference: Improving Cancer Risk Prediction for Prevention and Early Detection; Nov 16-19, 2016; Orlando, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2017;26(5 Suppl):Abstract nr IA10.