Use of [11C]Aminocyclohexanecarboxylate for the Measurement of Amino Acid Uptake and Distribution Volume in Human Brain

• Published in: Journal of cerebral blood flow and metabolism 1990-09, Vol.10 (5), p.727-739
• Main Authors: Koeppe, Robert A., Mangner, Thomas, Betz, A. Lorris, Shulkin, Barry L., Allen, Richard, Kollros, Peter, Kuhl, David E., Agranoff, Bernard W.
• Format: Article
• Language: English
• Subjects: 550601 - Medicine- Unsealed Radionuclides in Diagnostics; Adult; AMINO ACIDS; Amino Acids - pharmacokinetics; BETA DECAY RADIOISOTOPES; BETA-PLUS DECAY RADIOISOTOPES; Biological and medical sciences; BLOOD-BRAIN BARRIER; BODY; BRAIN; Brain - metabolism; CARBON 11; CARBON ISOTOPES; Carbon Radioisotopes; CARBOXYLIC ACIDS; CENTRAL NERVOUS SYSTEM; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Computer Simulation; COMPUTERIZED TOMOGRAPHY; Cycloleucine - pharmacokinetics; DIAGNOSIS; DIAGNOSTIC TECHNIQUES; DISEASES; EMISSION COMPUTED TOMOGRAPHY; EVEN-ODD NUCLEI; Fundamental and applied biological sciences. Psychology; Humans; ISOTOPES; LIGHT NUCLEI; MEMBRANE TRANSPORT; MINUTES LIVING RADIOISOTOPES; Models, Neurological; NERVOUS SYSTEM; NERVOUS SYSTEM DISEASES; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANS; PATIENTS; PERMEABILITY; POSITRON COMPUTED TOMOGRAPHY; RADIOISOTOPES; RADIOLOGY AND NUCLEAR MEDICINE; TOMOGRAPHY; Tomography, Emission-Computed; Vertebrates: nervous system and sense organs
• ISSN: 0271-678X; 1559-7016
• DOI: 10.1038/jcbfm.1990.126

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 ∼0.03–0.04 ml g−1 min−1, indicating a single-pass extraction fraction of ∼5–7%. The intersubject coefficient of variation was ∼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.