Abstract 2071: The utility of FDG uptake as a surrogate biomarker to monitor tumor cell metabolism in response to anticancer therapy

Abstract

Abstract [18F]FDG-PET imaging has been emerging as a powerful clinical tool for tumor diagnosis, staging and monitoring anticancer therapy. Due to some physiologic variants and technical artifacts, one of the limitations for [18F]FDG-PET imaging is the potential to show negative scans despite the presence of malignant tumors. In this report, we aimed to gain insights into the FDG tracer biology in different tumor models and subsequently to validate the use of FDG tracer uptake for monitoring targeted therapy. To measure the FDG tracer uptake in tumor cells, a LC/MS method was established to monitor the FDG monophosphate; these results were compared with the outcome of [18F]FDG-PET imaging. In a subset tumor models including patient derived xenografts, not all growing tumors showed high FDG tracer avidity. RT-PCR and IHC assays were performed to understand the potential physiological factors that could impact the FDG tracer avidity including the intrinsic glucose level, the exposure and distribution of FDG, as well as the expressions of glucose transporters and hexokinase. The results indicated that LC/MS analysis of FDG monophosphate served as a cost-effective tool to provide a surrogate measure of [18F]FDG-PET imaging. By using FDG tracer avid tumor models, several anticancer agents including the PI3K/mTOR dual inhibitor PF-04691502, crizotinib and the γ-Secretase inhibitor PF-03084014 demonstrated suppression in FDG tracer uptake after treatment, which predicted their antitumor efficacies in the corresponding models. This work provides insights into the FDG tracer biology and the utility of [18F]FDG-PET imaging as a non-invasive biomarker for anticancer drug discovery. Citation Format: Nanni Huser, Wenlin Li, Maruja Lira, Patrick Lappin, Erick Kindt, Valeria Fantin, Gary Li, Cathy C. Zhang. The utility of FDG uptake as a surrogate biomarker to monitor tumor cell metabolism in response to anticancer therapy. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2071. doi:10.1158/1538-7445.AM2014-2071