BRAIN EXTRACTION AND DISTRIBUTION OF TC-99M-BICISATE IN HUMANS AND INRATS

Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L -cystein diethylester (bicisate, ECD) was measured repeatedly in five patients by means of the intravenous (i.v.) double-indicator technique using Na-24(+) as an intravascular cotracer. After i.v. injection, th e arterial concentration curve of Tc-99m-bicisate was delayed and disp ersed compared with that of the intravascular cotracer, presumably due to lung retention of the flow tracer. The corrected cerebral venous o utput curves were fitted using a three-compartment model with four par ameters. At resting cerebral blood flow (CBF) values, the unidirection al brain extraction was 0.57 +/- 0.05, the permeability-surface area p roduct for passage from blood to brain (PS1) was 0.48 +/- 0.07 ml/g/mi n, and the distribution volume for bicisate was 0.74 +/- 0.20 (mean +/ - SD). In a single patient, BBB transport after i.v. injection of bici sate was compared with that of a similar flow tracer, d,l-hexamethylpr opyleneamine oxime (HM-PAO), and similar values were found for the two tracers. In 19 rats, the brain extraction of bicisate was measured by means of the intracarotid double-indicator technique. The brain extra ction was measured at resting, decreased, and increased CBF values. Lo w CBF values were obtained by hyperventilation and high values by hype rcapnia. The degree of backflux of tracer from brain to blood was eval uated by means of the three-compartment model and was found to be negl igible in these experiments. The brain extraction was 0.70 +/- 0.1 and PS1 was 0.94 +/- 0.27 ml/g/min. During hypercapnia, CBF increased fro m 0.77 to 1.09 ml/g/min, leading to a significant decrease in brain ex traction, from 0.70 to 0.56. During hyperventilation, CBF decreased fr om 0.77 to 0.54 ml/g/min, leading to a significant increase in brain e xtraction, from 0.70 to 0.74. PS1 remained constant despite changes in CBF or bolus size.