Analysis of Time Courses of Metabolic Precursors and Products in Heterogeneous Rat Brain Tissue: Limitations of Kinetic Modeling for Predictions of Intracompartmental Concentrations from Total Tissue Activity

The efficacy of various kinetic models to predict time courses of total radioactivity and levels of precursor and metabolic products was evaluated in heterogeneous samples of freeze-blown brain of rats administered [14C]deoxyglucose ([14C]DG). Two kinetic models designed for homogeneous tissues, i.e., a no-product-loss, three-rate-constant (3K) model and a first-order-product-loss, four-rate-constant (4K) model, and a third kinetic model designed for heterogeneous tissues without product loss [Tissue Heterogeneity (TH) Model] were examined. In the 45-min interval following a pulse of [14C]DG, the fit of the TH Model to total tissue radioactivity was not statistically significantly better than that of the 3K Model, yet the TH Model described the time courses of [14C]DG and its metabolites more accurately. The TH- and 4K-Model-predicted time courses of [14C]DG and its metabolites were similar. Whole-brain glucose utilization (CMRglc) calculated with the TH or 3K Model, ∼75 μmol 100 g−1 min−1, was similar to...