Abstract 3219: DrIMS-3DCC: Drug imaging mass spectrometry of 3D cell culture systems.

Abstract

Abstract 3D cell cultures have increased complexity compared to simple monolayer and suspension cultures, recapitulating the cellular architecture in the body. For example, many colon cancer cell lines form rounded heterogeneous spheroid structures that mimic the pathophysiological properties of tumors when grown under appropriate cell culture conditions. Classical imaging methodologies, like immunohistochemistry, are commonly used to examine the distribution of specific species within the spheroids. However, there is a need for an unbiased discovery-based methodology that would allow examination of protein/peptide distributions in 3D culture systems, without a need for prior knowledge of the analytes. We have developed a MALDI imaging mass spectrometry approach to examine protein distributions in 3D culture models (MALDI IMS-3DCC), allowing us to map the spatiotemporal dynamics of proteins in these valuable model systems. We are currently expanding our approach to image the distribution of drugs within 3D cell cultures. We are using our MALDI IMS-3DCC to analyze the penetration of drugs within 3D cell cultures. With our mass-spectrometric based approach, we have the ability to map the distribution of the 1) the drug, 2) the metabolites produced from the drug, and 3) the spatiotemporal changes in proteins following treatment. Thus far, we have successfully evaluated the effects of two clinically relevant species, oxaliplatin and Irinotecan, on spheroids. In the future, we will expand our approach to evaluate new therapeutic compounds. We believe that our novel imaging strategy will drastically alter how new therapeutic compounds are evaluated, reducing the need for animal models in the early stages of drug development, thereby speeding up the drug evaluation process. Citation Format: Xin Liu, Eric Weaver, Amanda B. Hummon. DrIMS-3DCC: Drug imaging mass spectrometry of 3D cell culture systems. [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 3219. doi:10.1158/1538-7445.AM2013-3219