Abstract
Molecular imaging of tissue hypoxia generates contrast in hypoxic areas by applying hypoxia-specific tracers in organisms. In cancer tissue, the injected tracer needs to be transported over relatively long distances and accumulates slowly in hypoxic regions. Thus, the signal-to-background ratio of hypoxia imaging is very small and a non-specific accumulation may suppress the real hypoxia-specific signals. In addition, the heterogeneous tumor microenvironment makes the assessment of the tissue oxygenation status more challenging. In this study, the diffusion potential of oxygen and of a hypoxia tracer for 4 different hypoxia subtypes: ischemic acute hypoxia, hypoxemic acute hypoxia, diffusion-limited chronic hypoxia and anemic chronic hypoxia are theoretically assessed. In particular, a reaction-diffusion equation is introduced to quantitatively analyze the interstitial diffusion of the hypoxia tracer [18F]FMISO. Imaging analysis strategies are explored based on reaction-diffusion simulations. For hypoxia imaging of low signal-to-background ratio, pharmacokinetic modelling has advantages to extract underlying specific binding signals from non-specific background signals and to improve the assessment of tumor oxygenation. Different pharmacokinetic models are evaluated for the analysis of the hypoxia tracer [18F]FMISO and optimal analysis model were identified accordingly. The improvements by model-based methods for the estimation of tumor oxygenation are in agreement with experimental data. The computational modelling offers a tool to explore molecular imaging of hypoxia and pharmacokinetic modelling is encouraged to be employed in the corresponding data analysis.
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This study was supported by the German Research Foundation (DFG), Collaborative Research Centre (SFB) 824.
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Shi, K., Ziegler, S.I., Vaupel, P. (2016). Molecular Imaging of Tumor Hypoxia: Existing Problems and Their Potential Model-Based Solutions. In: Luo, Q., Li, L., Harrison, D., Shi, H., Bruley, D. (eds) Oxygen Transport to Tissue XXXVIII. Advances in Experimental Medicine and Biology, vol 923. Springer, Cham. https://doi.org/10.1007/978-3-319-38810-6_12
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DOI: https://doi.org/10.1007/978-3-319-38810-6_12
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