Abstract 2864: Molecular imaging of early inflammatory response during hyperplasia and/or colitis in response to bacterial infection.

Abstract

Abstract Inflammatory diseases such as ulcerative colitis recruit myeloid cells and result in inflammatory responses such as generation of reactive oxygen species (ROS). Development of non-invasive luminescence imaging approaches is needed to evaluate these inflammatory responses. We developed methodologies to show that vibration induced gut inflammation can be determined using luminescence imaging approach in a non-invasive fashion (Papineni and Vizard, World Molecular Imaging Congress 2012). Citrobacter rodentium (CR) is a natural bacterial pathogen that infects the distal colon of mice and induces transmissible murine colonic hyperplasia (TMCH). Here we determined the early inflammatory response (ROS activity) to intestinal infection by CR in a longitudinal study. We further assessed the effects of allelic variation on murine chromosome 11 (B6.CAST. 11) on the inflammatory response. The ROS activity was monitored in real-time in vivo using L-012 (8-amino-5-chloro-7-phenylpyridol [3,4-d]pyridazine-1,4(2H,3H) dione), a chemiluminescence reporter, using planar multimodal imaging system. 0.1 ml of 1 mg/ml L-012 probe was injected (i.p.) in control and the experimental mice that were subjected to CR infection. Necrosis was imaged (post-infection day-19) using a fluorescent probe containing a bis (zinc2+dipicolylamine, Zn- DPA) motif which binds with high affinity to apoptotic, necrotic, and bacterial surfaces. Significant difference in the basal gut ROS activity was found in mice with allelic variation on chromosome 11 compared to the wild type littermates. Robust elevation in ROS activity was observed in both the wild type and B6.CAST.11mice that were infected with CR (post infection 9, 12, 19 days). The variation in the levels of ROS activity however was very distinct between the wild type and B6.CAST.11 mice indicating the contribution of molecular determinants at the chromosome 11. The potential advantages in these real-time ROS monitoring methodologies by in vivo imaging, in understanding mechanisms of infection, inflammation, and development of better intervention strategies will be elaborated. Citation Format: Rao Papineni, Ishfaq Ahmed, Steven LeVine, Kenneth Bradley, William Mclaughlin, John Pizzonia, Shahid Umar. Molecular imaging of early inflammatory response during hyperplasia and/or colitis in response to bacterial infection. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2864. doi:10.1158/1538-7445.AM2013-2864