Blood-brain barrier, half-time disappearance, and brain distribution for labeled enkephalin and a potent analog.

The natural opiate methionine-enkephalin and its D-alanine2 analog were iodinated by a method involving lactoperoxidase and purified by partition chromatography on Sephadex G-25. The half-time disappearance of radioactivity was determined in blood obtained from the jugular vein after injection of the iodinated methionine-enkephalin into the carotid artery or jugular vein and found to be less than a minute. Despite a greater potency and more prolonged activity of D-alanime2-methionine-enkephalin as compared with methionine-enkephalin, the half-time disappearance of radioactivity after injection of the iodinated analog was about the same, its distribution volume tended to be smaller, and the retention of counts in the brain was significantly less then after the iodinated parent compound. There was little statistical difference in the accumulation of radioactivity among nine brain regions 5 sec after the rapid injection of tritiated methionine-enkephalin into the carotid artery in contrast with the accumulation found after similar injection of tritiated tyrosine or tritiated water. The ratio of radioactivity in the pituitary or pineal to that in the brain parts within the blood-brain barrier was much greater after administration of the tritiated enkephalin than after the tritiated water. A modified brain-uptake index (BUI) value of 15 for the tritiated enkephalin indicates that methionine-enkephalin crosses the blood-brain barrier.