Multimodal Approach for Imaging Hypoxia in a Lewis Lung Carcinoma Tumor Model

Abstract

Purpose: To assess feasibility of detecting and differentiating hypoxic and necrotic regions within a murine syngeneic subcutaneous tumor model using a combination of magnetic resonance imaging (MRI) and 18F-FMISO and 18F-FDG positron emission tomography (PET). Materials and methods: The study was performed on three C57Bl/6 mice bearing subcutaneous Lewis lung carcinoma (LLC) xenografts. All animals underwent sequential (with a 24-hour interval) 18F-FMISO PET/CT and 18F-FDG PET/CT, as well as T1-weighted MRI to assess tumor volume and areas of impaired blood flow. Quantitative analysis of standardized uptake values (SUV) and volumes was performed. Results: 18-F-FMISO PET visualized hypoxic zones in two mice and a zone of hypofixation (suggestive of necrosis) in one mouse, whereas 18F-FDG PET across all cases demonstrated ring-like peripheral uptake. An inverse correlation between 18F-FDG SUV and tumor volume was observed, while no such correlation was found for 18F-FMISO. Comparison of the total functional volume (derived from PET data) with the anatomical volume (derived from MRI data) suggested the presence of necrosis in one mouse. Conclusion: The combined use of MRI, 18F-FMISO PET and 18F-FDG PET provides non-invasive functional characterization of the LLC tumor model and facilitates differentiation between hypoxic and necrotic zones; however, the approach has methodological limitations related to the time interval between scans.