Brain Uptake of [C-13] and [C-14]Sucrose Quantified by Microdialysis and Whole Tissue Analysis in Mice

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Among small, hydrophilic drug-like molecules, [14C]sucrose has long been considered the gold standard for determination of blood-brain barrier (BBB) permeability. However, we have recently shown in rats that, compared with LC-MS/MS analysis of stable isotope (13C) of sucrose, [14C]sucrose significantly overestimates the brain tissue concentration and uptake of sucrose by a factor of 6-7. This discrepancy is due to the presence of small quantities of lipophilic impurities in [14C]sucrose tracer solutions. Here, we utilized intracranial microdialysis to measure concentrations of both sucrose variants in brain extracellular fluid (ECF) after IV bolus administration to mice. Both markers displayed similar plasma profiles and ECF dialysate concentrations. However, total brain tissue concentrations and apparent brain uptake clearance of [14C]sucrose were, respectively, 4.1- and 3.6-fold higher than those of [13C]sucrose. Therefore, the contaminants of [14C]sucrose with higher permeability were likely sequestered by brain cells, which renders them non-dialyzable. It is concluded that although measurement of radioactivity overestimates the concentrations of intact sucrose in the brain tissue, the ECF radioactivity after microdialysis is a relatively accurate reflection of intact sucrose after the systemic administration of the [14C]sucrose marker.


This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Drug Metabolism and Disposition, volume 46, issue 11, in 2018 following peer review. The definitive publisher-authenticated version is available online at


American Society for Pharmacology and Experimental Therapeutics (ASPET)