Fluorine-19 Magnetic Resonance Imaging and Positron Emission Tomography of Tumor-Associated Macrophages and Tumor Metabolism

The presence of tumor-associated macrophages (TAMs) is significantly associated with poor prognosis of tumors. Currently, magnetic resonance imaging- (MRI-) based TAM imaging methods that use nanoparticles such as superparamagnetic iron oxide and perfluorocarbon nanoemulsions are available for quantitative monitoring of TAM burden in tumors. However, whether MRIbased measurements of TAMs can be used as prognostic markers has not been evaluated yet. In this study, we used positron emission tomography (PET) with 18F-2-fluoro-2-deoxy-D-glucose (18F-FDG) as a radioactive tracer and fluorine-19- (19F-) MRI for imaging mouse breast cancer models to determine any association between TAM infiltration and tumor metabolism. Perfluorocarbon nanoemulsions were intravenously administered to track and quantify TAM infiltration using a 7T MR scanner. To analyze glucose uptake in tumors, 18F-FDG-PET images were acquired immediately after 19F-MRI. Coregistered 18F-FDG-PET and 19F-MR images enabled comparison of spatial patterns of glucose uptake and TAM distribution in tumors. 19F-MR signal intensities from tumors exhibited a strong inverse correlation with 18F-FDG uptake while having a significant positive correlation with tumor growth from days 2 to 7. These results show that combination of 19F-MRI and 18F-FDG-PET can improve our understanding of the relationship between TAM and tumor microenvironment.