Parametric in vivo imaging of benzodiazepine receptor distribution in human brain.
Emission computed tomographic methods for the in vivo quantification of radioligand-binding sites in human brain have previously been limited either by a lack of correction for possible effects of altered ligand transport or by highly complicated physiological models that preclude display of binding data in a detailed anatomical format. We investigated the application of a simplified compartmental model to the kinetic analysis of in vivo ligand binding to central benzodiazepine receptors. The human brain distribution of [11C]flumazenil, as determined by dynamic positron emission tomography, combined with metabolite-corrected arterial blood samples, permitted estimations of local cerebral ligand transport and of receptor binding. This approach allows calculation of transport and binding "maps" on a pixel-by-pixel basis, resulting in the display of binding data in a familiar tomographic format while maintaining much of the physiological accuracy inherent in more complex methods. The results obtained in a study of 6 normal volunteers revealed good interindividual precision, with coefficients of variation between 10 and 15% of mean regional values, suggesting the utility of this approach in future clinical studies of benzodiazepine receptor binding.
Frey
K A
KA
Division of Nuclear Medicine (Department of Internal Medicine) University of Michigan, Ann Arbor.
Holthoff
V A
VA
Koeppe
R A
RA
Jewett
D M
DM
Kilbourn
M R
MR
Kuhl
D E
DE
D000328:Adult; D001825:Body Fluid Compartments; D001921:Brain / Q000033:anatomy & histology*; D001923:Brain Chemistry; D001931:Brain Mapping; D005442:Flumazenil / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D008954:Models, Biological; D011963:Receptors, GABA-A / Q000032:analysis*; D014055:Tomography, Emission-Computed
D011963:Receptors, GABA-A; D005442:Flumazenil