Abstract 1480: Hot spot 19F MR imaging of inflammation predicts colitis-associated cancer

Abstract

Abstract Introduction: The causal relationship between inflammation and cancer is well established. In the colon, colitis-associated cancer (CAC) develops through complications of inflammatory bowel disease (IBD), including ulcerative colitis and Crohn's disease. CAC development is directly correlated with the severity and longevity of inflammation in IBD patients. We hypothesized that non-invasive serial MRI of inflammatory sites and measuring their severity may enable earlier diagnosis and prediction of cancer development. Methods: To induce CAC, female A/J mice (n = 5) were injected with azoxymethane (10mg/kg) on day 0 and fed with 2.5% dextran sodium sulfate (DSS) solution for every 3 weeks until week 7. 200 μl of perfluoro-15-crown-5-ether (PFC) emulsion (Celsense Inc., VS-580H), which labels macrophages, was injected through the tail vein 48 hours before the first MRI scan. In vivo MR imaging was performed every 15 days from day 50 to day 110 using a 11.7T MR scanner and a surface coil tunable to 1H and 19F. Conventional 1H (proton) images were acquired using a fast spin echo sequence (FSE) with RARE, TR/TE = 1200/30 ms, matrix size = 256×256, FOV = 3.2×2.0cm, rare factor = 8, and slice thickness = 2mm. “Hot spot” 19F (fluorine) images were acquired using an FSE with RARE, TR/TE = 1000/14ms, matrix size = 64×32, rare factor = 8, and slice thickness = 2mm. Ex vivo images were acquired with a 750 MHz microimaging system and a 25mm volume coil. Fixed colon tissues were paraffin-cut to evaluate tumor development. Multiple longitudinal colon segments were chosen from areas either with or without 19F signal. H&E stained sections from each segment were scored by a blinded pathologist for the severity of inflammation and presence of dysplasia. Results and Discussion: Hot spots of 19F signal were detected in the colon wall after the onset of IBD, with a patchy distribution pattern. Since PFC emulsions specifically label macrophages, these signals represent infiltrated macrophages in the colon wall as a result of inflammation driven by DSS. Tumor outgrowths were observed on MRI at the inflammatory sites starting at day 80. In vivo data were validated by ex vivo imaging of excised colon tissues showing an exact co-localization of tumors with the 19F-positive inflammatory sites. Histologically, tumors were classified as adenomas. CAC develops through the sequence of inflammation-adenoma-carcinoma suggesting that we were able to detect early stages of carcinomatous changes in the inflammatory sites. Histological scores of inflammation and adenoma showed a significant correlation with the intensity of 19F signals. We conclude that hot spot 19F MRI enables early diagnosis of future sites of colon cancer development. Citation Format: Soo-Hyun Shin, Deepak K. Kadayakkara, Jeff W. M Bulte. Hot spot 19F MR imaging of inflammation predicts colitis-associated cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1480. doi:10.1158/1538-7445.AM2015-1480