Abstract 3176: Preclinical validation of the sensitivity and specificity of a fluorescent nanobeacon for its application in colonoscopy-based imaging of colorectal cancer

Abstract

Abstract Colorectal cancer is the third most commonly diagnosed type of cancer and the second leading cause of cancer-related death in the U.S. Currently, the key element in the control, prevention, and treatment of this disease is recognition of its early symptoms. In this work, we describe the development and validation of a specific fluorescent nanobeacon that targets the Thomsen-Friedenreich (Tf) antigen, potential biomarkers of this disease, via the terminal carbohydrate Gal-β(1-3)GalNAc. The imaging agent is comprised of a submicron-sized polystyrene nanosphere encapsulated with a hydrophobic fluorescent dye. The surface of the nanosphere was modified with the peanut agglutinin (PNA) and poly(N-vinylacetamide (PNVA) moieties. The former binds to Gal-β(1-3)GalNAc with high affinity, while the latter enhances the specificity of PNA for the carbohydrates. This nanobeacon detects colorectal tumors by recognizing the tumor-specific antigen through the surface-immobilized PNA, and identification is made via the fluorescence signal obtained from the coumarin-6 encapsulated in the nanosphere's core. Biorecognition by the probe has been demonstrated in cell lines and orthotopic mouse models. Here, we assessed the sensitivity and specificity of the probe in a pre-clinical MUC1 transgenic mouse model. Of note, the probe reported that the Tf antigen expression level is high in the colon and intestine of that model compared to wild- type mice. Data obtained by fluorescence imaging using this probe correlates well with those obtained via immunohistochemistry. Most importantly, the probe was not absorbed systemically upon topical application in the host. As a result, no registered toxicity is associated with the probe. Using the Tf antigen imaging approach, we are evaluating the binding specificity of the nanobeacon in panel of human colorectal cancer tissues. Thus far, the study has indicated quantitatively a 5-fold enhancement of the Tf expression in colon cancer tissue versus the control tissue. In sum, these data demonstrate the potential for the use of this novel nanobeacon in imaging the Tf antigen as a biomarker for the early detection and prediction of the progression of colorectal cancer. Currently, several probe optimization processes are presently being carried out in our laboratory, including the incorporation of near-infrared fluorescent dyes to enhance the signal-to-noise ratio. Detailed results of the biometric validation of the nanobeacon will be reported in a timely manner. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 3176. doi:10.1158/1538-7445.AM2011-3176