Use of [11C]aminocyclohexanecarboxylate for the measurement of amino acid uptake and distribution volume in human brain.
A quantitative positron emission tomographic (PET) method to measure amino acid blood-brain barrier (BBB) transport rate and tissue distribution volume (DV) has been developed using 11C-labeled aminocyclohexanecarboxylate (ACHC), a nonmetabolized amino acid analogue. Dynamic PET data were acquired as a series of 15 scans covering a total of 60 min and analyzed by means of a two-compartment, two-parameter model. Functional images were calculated for the amino acid transport rate constants across the BBB and the amino acid DV in the brain. Results show [11C]ACHC to have an influx rate constant in gray matter of approximately 0.03-0.04 ml g-1 min-1, indicating a single-pass extraction fraction of approximately 5-7%. The intersubject coefficient of variation was approximately 15% while intrasubject variability of repeat scans was only slightly greater than 5%. Studies were performed in 15 young normal volunteer control subjects, 5 elderly controls, 7 patients with probable Alzheimer's disease, and one patient with phenylketonuria. Results indicate that [11C]-ACHC will serve as the basis of a method for measuring amino acid transport rate and DV in the normal and pathological human brain.
Koeppe
R A
RA
Department of Internal Medicine, University of Michigan Medical School, Ann Arbor 48109-0552.
Mangner
T
T
Betz
A L
AL
Shulkin
B L
BL
Allen
R
R
Kollros
P
P
Kuhl
D E
DE
Agranoff
B W
BW
D000328:Adult; D000596:Amino Acids / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D003198:Computer Simulation; D003515:Cycloleucine / Q000493:pharmacokinetics; D006801:Humans; D008959:Models, Neurological; D014055:Tomography, Emission-Computed
D000596:Amino Acids; D002250:Carbon Radioisotopes; D003515:Cycloleucine