Blood brain barrier permeability of ¹¹C labeled alcohols and ¹⁵O labeled water

The extraction of ¹¹C labeled methanol, ethanol, and isopropanol, as well as ¹⁵O labeled water by the brain during a single capillary transit, was studied in vivo in six adult rhesus monkeys by external detection of the time course of these tracers subsequent to their internal carotid artery injection. The data demonstrate the feasibility of accurately measuring brain permeability of highly diffusible substances by this technique and show that neither water nor the alcohols studied freely equilibrate with brain when the cerebral blood flow exceeds 30 ml/100 g min^-1. At a cerebral blood flow of 50 ml/100 g min^-1 only about 93% of an injected bolus of labeled water freely exchanges with brain, compared with methanol (93%), ethanol (97%), and isopropanol (99%). The brain capillary permeability surface area (PS) products computed from these data were 0.023 cm³/s g^-1 (water), 0.024 cm³/s g^-1 (methanol), 0.030 cm³/s g^-1 (ethanol), and 0.062 cm³/s g^-1 (isopropanol). This sequence of PS products is consistent with the individual lipid solubilities of the alcohols studied and underscores the unique brain permeability characteristics of lipid insoluble water.