In vivo determination of the kinetic parameters of glucose transport in the human brain using ¹¹C-methyl-d-glucose (CMG) and dynamic positron emission tomography (dPET)

Abstract

A method was developed to measure simultaneously (1) the rate constants for glucose influex and glucose efflux, and (2) the Michaelis-Menten constant (K _M ) and maximal velocity (V _max) for glucose transport across the blood-brain barrier (BBB) in any selected brain area. Moreover, on the basis of a mathematical model, the local perfusion rate (LPR) and local unidirectional glucose transport rate (LUGTR) are calculated in terms of parameters of the time-activity curves registered over different brain regions; ¹¹C-methyl-d-glucose (CMG) is used as an indicator. The transaxial distribution of activity in the organism is registered using dynamic positron-emission tomography (dPET). The method was used in 4 normal subjects and 50 patients with ischemic brain disease. In normals, the rate constant for CMG efflux was found to be 0.25±0.04 min^-1 in the cortex and 0.12±0.02 min^-1 in white matter. In the cortex, the K _M was found to be 6.42 μmol/g and the V _max was 2.46 μmol/g per minute. The LUGTR ranged from 0.43 to 0.6 μmol/g per minute in the cortex, and from 0.09 to 0.12 μmol/g per minute in white matter. The LPR was calculated to be 0.80–0.98 ml/g per minute for the cortex and 0.2–0.4 ml/g per minute for white matter. In patients with stroke, the ischemic defects appeared to be larger in CMG scans than in computed x-ray tomography (CT) scans. Prolonged reversible ischemic neurological deficit was associated with a significant fall in the LUGTR but no change in the LPR in the corresponding cerebral cortex. Normal LUGTR and significantly decreased LPR were registered in a patient with progressive occlusion of the middle cerebral artery. In a patient with transient ischemic attacks, a slightly reduced LPR and a disproportionally reduced LUGTR were observed before operation. After extra- and intrac-ranial bypass surgery, the LPR became normal, whereas the LUGTR increased but did not achieve normal values.