Relationship between lipophilicity and brain extraction of C-11-labeled radiopharmaceuticals

The brain extraction of fifteen C-11-labeled compounds during a single capillary transit was studied in adult baboons by external detection of these tracers after injection into the internal carotid artery. The log P(oct) (partition coefficient for octanol/water) values of these compounds range from -0.7 to greater than 4.0. A parabolic relationship was found between the log P(oct) value of the C-11-labeled compounds and the fraction of the radiopharmaceutical entering the brain. Compounds with log P(oct) values between 0.9 and 2.5 were found to pass freely across the blood-brain barrier at a cerebral flow of 100 mlxmin^-1xhg^-1. An apparently decreased extraction of very lipophilic compounds was shown to be related to binding of the tracer to blood components and macromolecules (red blood cells, albumin, etc.). These data suggest that a radiopharmaceutical designed to measure blood flow should have a log P(oct) value of between 0.9 and 2.5.