Abstract 4330: Effects of isofluran anesthesia on bioluminescence measurements: impact on pharmacological assessment of antitumor activity of chemical entities

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Bioluminescence imaging (BLI) has been used for several years in oncology research to quantify tumor growth. In order to allow immobilization during data acquisition, animals are usually anesthetized by isoflurane gas inhalation. However, anesthesia leads to modifications of many physiological parameters, and particularly decreases in heart rate, blood pressure and blood flow, leading to decrease of substrate availability. Thus, it can be postulated that anesthesia will impair bioluminescence read outs. This may in turn profoundly affect interpretation of compound activity based on BLI. We have investigated the difference in BLI measurements performed in conscious and anesthetized animals using subcutaneous xenografts (HCT116 colorectal and U87MG glioblastoma) and orthotopic (U87MG cells injected directly in the brain) models. Moreover, functional tumor vessel mapping and hypoxia stage were obtained using casting technology and HypoxyProbeTM, respectively. Anti-tumor activity of 5-fluorouracil and temozolomide were assessed in the HCT116 xenograft and U87MG orthotopic models, respectively. Our results have clearly demonstrated that in all tested tumor models, tumor growth and efficacy of different compounds were not affected by the regular anesthesia procedure used for bi-weekly BLI assessments. We found a good correlation between caliper and BLI over a wide range of tumor size in conscious mice. When BLI was measured in anesthetized mice, signal intensity dropped significantly up to 70%, impairing the assessment of the antitumor efficacy of 5-FU. A clear correlation to functional tumor vessel density was evidenced. In the U87MG tumors cells implanted intracranialy, we could clearly follow tumor growth over time using BLI readouts. Isoflurane did not impair BLI measurements or the efficacy profile of temozolomide. In conclusion, we can say that BLI measurements in conscious tumor bearing mice offers a better alternative for resolving pharmacologic queries without the confounding effects of anesthesia. Obviously, more extended studies over a wide range of tumor types will be needed to reinforce these conclusions. Moreover, a more quantitative approach to assess vessel density and distribution in the casts using micro-CT technologies would be pivotal. Note: This abstract was not presented at the AACR 101st Annual Meeting 2010 because the presenter was unable to attend. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4330.