Brain extraction and distribution of 99mTc-bicisate in humans and in rats.

Blood-brain barrier (BBB) passage of the flow tracer ethylenediylbis-L-cysteine diethylester (bicisate, ECD) was measured repeatedly in five patients by means of the intravenous (i.v.) double-indicator technique using {sup 24}Na{sup +} as an intravascular cotracer. After i.v. injection, the arterial concentration curve of {sup 99m}{Tc}-bicisate was delayed and dispersed compared with that of the intravascular cotracer, presumably due to lung retention of the flow tracer. The corrected cerebral venous output curves were fitted using a three-compartment model with four parameters. At resting cerebral blood flow (CBF) values, the unidirectional brain extraction was 0.57 {+-} 0.05, the permeability-surface area product for passage from blood to brain (PS{sub 1}) was 0.48 {+-} 0.07 ml/g/min, and the distribution volume for bicisate was 0.74 {+-} 0.20 (mean {+-} SD). In a single patient, BBB transport after i.v. injection of bicisate was compared with that of a similar flow tracer, d,l-hexamethylpropyleneamine 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 extraction was measured at resting, decreased, and increased CBF values. Low CBF values were obtained by hyperventilation and high values by hypercapnia. The degree ofmore » backflux of tracer from brain to blood was evaluated by means of the three-compartment model and was found to be negligible in these experiments. The brain extraction was 0.70 {+-} 0.1 and PS{sub 1} was 0.94 {+-} 0.27 ml/g/min. During hypercapnia, CBF increased from 0.77 to 1.09 ml/g/min, leading to a significant decrease in brain extraction, from 0.70 to 0.56. During hyperventilation, CBF decreased from 0.77 to 0.54 ml/g/min, leading to a significant increase in brain extraction, from 0.70 to 0.74. PS{sub 1} remained constant despite changes in CBF or bolus size. 12 refs., 5 figs., 3 tabs.« less