Kinetics and distribution volumes for tracers of different sizes in the brain plasma space.
Regional brain and plasma concentrations were determined for a series of radiotracers that differ in molecular weight and size in pentobarbital-anesthetized rats at 1, 5 and 30 min after i.v. injection. The tracers, [3H]inulin (mol. wt. 5000 Da, radius 1.5 nm), 5 [3H]dextrans (10,000-200,000 Da, 2.3-9.5 nm) and [51Cr]transferrin (79,000 Da, 3.8 nm), are not taken up into erythrocytes and do not measurably cross the blood-brain barrier in 30 min. Results were expressed as a brain distribution volume, defined as (dpm/g brain)/(dpm/ml plasma). Within 1 min after injection, all tracers attained an initial distribution volume which varied regionally from 0.4 to 1.6 X 10(-2) ml/g. The volumes remained constant between 1 and 30 min for tracers with radii greater than or equal to 3.8 nm, whereas the volumes increased up to 90% for tracers with radii less than or equal to 3.1 nm. Rates of equilibration for tracers with radii less than or equal to 3.1 nm were size dependent with smaller tracers equilibrating before larger tracers. These results indicate that the brain distribution volume for plasma tracers consists of two compartments: one which is quickly filled (less than or equal to 1 min) by all tracers and comprises approximately 60% of the total volume, and one which allows only tracers with radii less than or equal to 3.1 nm and comprises 40% of the total volume. The inverse relation between the rate of equilibration in the second compartment and molecular size may indicate a diffusion limitation.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
Q R
QR
Laboratory of Neurosciences, National Institute on Aging, Bethesda, MD 20892.
Ziylan
Y Z
YZ
Robinson
P J
PJ
Rapoport
S I
SI
D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D003911:Dextrans / Q000493:pharmacokinetics*; D007444:Inulin / Q000493:pharmacokinetics*; D008297:Male; D008970:Molecular Weight; D010949:Plasma / Q000378:metabolism; D051381:Rats; D013395:Sucrose / Q000493:pharmacokinetics; D014168:Transferrin / Q000493:pharmacokinetics*
D003911:Dextrans; D014168:Transferrin; D013395:Sucrose; D007444:Inulin