Abstract 18 F-fluorodeoxyglucose ( 18 FFDG) positron emission tomography (PET), combined with compartmental modeling, is a powerful non-invasive imaging method for assessing cellular metabolism. However, classical two- and three-tissue compartment models assume homogeneous 18 FFDG distribution within the tissue, which needs justification, and the definition and interpretation of rate constants across these models is not always consistent. To address these issues, we develop a finite difference solver to simulate 18 FFDG transport and metabolism within a 1 mm 3 tissue volume, representing the smallest volume resolvable by PET. Our simulations reveal sub-millimeter heterogeneity in 18 FFDG distribution and show that the measured PET signal is dependent not only on cellular metabolic activity but also on interstitial 18 FFDG diffusivity, vascular permeability, and vascular architecture. We further demonstrate that our finite-difference simulation reduces to a three-tissue compartment model when interstitial 18 FFDG concentration is homogeneous. Furthermore, this simplified model itself reduces to the two-tissue compartment model when vascular permeability is sufficiently high. This work quantitatively links vascular permeability, vascular architecture, cellular uptake kinetics, 18 FFDG diffusivity, and acquisition time. It also unifies the two- and three-tissue compartment models and identifies their applicable regimes. These findings deepen our understanding of 18 FFDG transport kinetics and enhance the interpretability of dynamic 18 FFDG-PET imaging.
Zhong et al. (Thu,) studied this question.