Extraction of [99mTc]-d,l-HM-PAO across the blood-brain barrier

Abstract

The initial extraction (E) across the blood-brain barrier (BBB) of [99mTc]-d,l-HM-PAO after intracarotid injection was measured in 14 Wistar rats and 6 patients using the double indicator, single injection method with Na-24 as a cotracer. In both series, cerebral blood flow (CBF) was measured using the initial slope of the xenon-133 washout curve after intracarotid bolus injection. In rats, bolus size (20 or 120 μl), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF (p < 0.001): With a small bolus of saline and at resting CBF (0.75 ml/g/min), E was 0.81, decreasing to 0.56 at high CBF (1.5 ml/g(min). The calculated permeability surface area product (PS) increased linearly from 1.2 to 1.5 ml/g/min when CBF increased from 0.8 to 1.5 ml/g/min (p < 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 μl, while using a 120 μl bolus containing 10% albumin resulted in a decrease in E. This suggests that HM-PAO binding to albumin is not totally and rapidly reversible during a single passage through brain capillaries and that binding to blood elements may reduce the apparent extraction across brain capillaries. In patients using a a bolus of 1 ml saline, E decreased linearly with increasing CBF (r = -0.81, p < 0.001). For a CBF of 0.59 ml/g/min and an average apparent E of 0.72, an apparent PS product of 0.76 ml/g/min was calculated. Analysis of the apparent E vs. time profiles indicated as backdiffusion of the tracer during the experimental period. This could lead to a small underestimation of the actual extraction values.