PT  - JOURNAL ARTICLE
AU  - Faleh Alqahtani
AU  - Ekram Ahmed Chowdhury
AU  - Raktima Bhattacharya
AU  - Behnam Noorani
AU  - Reza Mehvar
AU  - Ulrich Bickel
TI  - Brain Uptake of [<sup>13</sup>C] and [<sup>14</sup>C]Sucrose Quantified by Microdialysis and Whole Tissue Analysis in Mice
AID  - 10.1124/dmd.118.082909
DP  - 2018 Nov 01
TA  - Drug Metabolism and Disposition
PG  - 1514--1518
VI  - 46
IP  - 11
4099  - http://dmd.aspetjournals.org/content/46/11/1514.short
4100  - http://dmd.aspetjournals.org/content/46/11/1514.full
SO  - Drug Metab Dispos2018 Nov 01; 46
AB  - Among small, hydrophilic drug-like molecules, [14C]sucrose has long been considered the gold standard for determination of blood-brain barrier permeability. However, we have recently shown in rats that, compared with liquid chromatography–tandem mass spectrometry analysis of stable isotope (13C) of sucrose, [14C]sucrose significantly overestimates the brain tissue concentration and uptake of sucrose by a factor of 6 to 7. This discrepancy is due to the presence of small quantities of lipophilic impurities in [14C]sucrose tracer solutions. Here, we used intracranial microdialysis to measure concentrations of both sucrose variants in brain extracellular fluid (ECF) after intravenous 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 4.1- and 3.6-fold higher, respectively, than those of [13C]sucrose. Therefore, the contaminants of [14C]sucrose with higher permeability were likely sequestered by brain cells, which renders them nondialyzable. 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.