Positron Emission Tomographic Measurements of Cerebral Glucose Utilization Using [1-11C]D-Glucose

Abstract

Regional CMR_glc was measured in seven healthy volunteers with positron emission tomography using [1-¹¹C]D-glucose. Regional CBF was measured using [¹¹C]fluoromethane. The arteriovenous differences of unlabeled glucose and oxygen together with ¹¹C metabolites were also measured. In addition to the loss of [¹¹C]CO₂, a loss of acidic ¹¹C metabolites was also detected. A three-compartment model was applied to the tracer data in the time interval 0–24 min. After correction for the loss of ¹¹C metabolites, the tracer method gave an average CMR_glc of 26.4 ± 1.9 (SD) μmol/100 g/min, close to the value obtained with the Fick principle. After correction for the loss of [¹¹C]CO₂ only, the tracer method gave 23.6 ± 2.1 μmol/100 g/min, compatible with (1/6) CMRO₂, obtained with the Fick principle. These results and the time course of the loss of acidic ¹¹C metabolites are consistent with the presence of nonoxidative metabolism of glucose that causes an early loss of mainly [¹¹C]lactate after a bolus injection of the tracer. This implies that [1-¹¹C]D-glucose measures the rate of glucose oxidation rather than the total CMR_glc. The experiments using [1-¹¹C]D-glucose were compared to five analogous experiments using [U-¹¹C]D-glucose together with [¹⁵O]H₂O as a flow tracer. After correction for the loss of [¹¹C]CO₂, the two glucose tracers gave similar global values of CMR_glc and other parameters associated with glucose utilization, but with labeling in the carbon-1 position, the loss of [¹¹C]CO₂ was substantially delayed and the contrast between gray and white matter was improved. A kinetic model for [1-¹¹C]D-glucose for use in PET studies without the simultaneous measurement of rCBF and the loss of ¹¹C metabolites is proposed.