Abstract 4236: Comparison of optical imaging approaches in 2D and 3D in disseminated mouse tumor models

Abstract

Abstract Introduction: Optical imaging allows staging and tracking of multiple tumors in disseminated tumor models and to this end, bioluminescence (BLI) imaging has been the most common approach. While BLI is cost effective and quantitative, it requires luciferase-engineered tumor lines, which have the disadvantages of time and uncertainty associated with transfection, as well as potential phenotype change in the engineered line, compared with the parent. Exogenous fluorescence probes preferentially activated by tumors provide a similar efficient optical imaging means to tumor burden tracking in these models, directly in any tumor lines of interest. This methods also allows 3D imaging through new tomographic optical imaging technologies. In this work, BLI and activated fluorescent probe imaging were used in a luciferase-expressing Raji-luc human Burkitt's lymphoma model and an M-NFS-60 mouse leukemia model. 2D fluorescence reflectance imaging was also compared to 3D tomographic imaging to determine additional utility of the 3D imaging approach. Methods: Raji-luc lymphoma cells were transfected to express luciferase using a lentiviral vector transfection method. Raji-luc cells (1x107 cells in 100µl PBS) were injected IV in CB-17 mice on Day 0. In CD-1 mice, M-NFS-60 leukemia cells (1x107 cells in 100µl PBS) were injected IP. Bioluminescence scans were used to determine the distribution of light throughout the body immediately following implantation. In vivo and ex vivo bioluminescence imaging was used to localize tumor signals and determine incidence and tumor growth. Both cathepsin- (ProSense) and MMP- (MMPSense) activated fluorescent probes were injected IV 24h prior to fluorescence reflectance and fluorescence molecular tomographic imaging. Results and Discussion: Bioluminescence imaging of intravenously injected of Raji-luc cells from one to four weeks after inoculation showed a high incidence of tumor growth at sites including hind limbs, spine, and brain in addition to lung and to a lesser extent, the axillary lymph nodes and sternum. Fluorescence imaging with tumor activated probes provided a measure of disseminated tumor burden, but had the disadvantage of normal tissue background, compared with BLI where there was inherently no normal tissue background. Fluorescence molecular tomographic imaging provided a quantitative advantage over 2D fluorescence reflectance. Activated fluorescent probe imaging provides a viable means for imaging in disseminated tumor models without the need for engineered cell lines. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4236. doi:1538-7445.AM2012-4236