Extraction of [99mTc]-d,l-HM-PAO across the blood-brain barrier.
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 the 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 microliters), bolus type (saline or 10% albumin), or CBF were changed. First-pass extraction was dependent on CBF (p less than 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 a 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 less than 0.01). E was found to increase when the bolus volume of saline was increased from 20 to 120 microliters, while using a 120 microliters 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 bolus of 1 ml saline, E decreased linearly with increasing CBF (r = -0.81, p less than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
Andersen
A R
AR
Department of Neurology, Rigshospitalet, Copenhagen, Denmark.
Friberg
H
H
Knudsen
K B
KB
Barry
D I
DI
Paulson
O B
OB
Schmidt
J F
JF
Lassen
N A
NA
Neirinckx
R D
RD
D000818:Animals; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D002560:Cerebrovascular Circulation; D006801:Humans; D008297:Male; D009942:Organometallic Compounds / Q000032:analysis / Q000378:metabolism*; D010091:Oximes / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013667:Technetium / Q000032:analysis / Q000378:metabolism*; D019690:Technetium Tc 99m Exametazime
D009942:Organometallic Compounds; D010091:Oximes; D019690:Technetium Tc 99m Exametazime; D013667:Technetium