A reaction-diffusion simulation model of [18F]FDG PET imaging for the quantitative interpretation of tumor glucose metabolism

Abstract

Positron emission tomography (PET) using 18F-fludeoxyglucose ([18F]FDG) improves the cancer diagnosis by visualizing the pathological pathway of Warburg effect. As an analog of glucose, FDG uptake is mediated by glucose transporter (GLUT) and hexokinase (HK), which can be overexpressed under tumor hypoxia conditions. Quantitative interpretation of the images to the feature of tumor microenvironment is important to improve tumor staging and localization. However, it is usually difficult for such kind of quantitative analysis due to the complex metabolic procedure of multi-substance system within tumor. This study proposes a novel reaction-diffusion model to simulate the procedures of FDG: transported into tumor cells, catalyzed by GLUT and phosphorylated by HK leading to the production of FDG-6-phosphate (FDG6P) similar to glucose-6-phosphate (G6P). Hypoxia induced factor-1 (HIF-1) is incorporated to control the upregulations of GLUT and HK. The simulation results are compared with dynamic PET scans of nude mice with lymphoma xenograft tumors, which confirmed that the simulation can approach to real measurements.With this quantitative simulationmodel, the interaction of FDGto the substances, oxygen, HIF-1, glucose, G6P, and FDG6P within the tumor microenvironment is investigated under various vascularizations. By controlling the expression factor of GLUT and HK, their influences on FDG uptake is further assessed. The preliminary results of the simulation model have shown a potential to improve the quantification of FDG PET image and to assist cancer diagnosis and therapy prognosis.