Cerebral glucose use measured with [14C]glucose labeled in the 1, 2, or 6 position

[6-14C]Glucose is the tracer sometimes recommended to assay cerebral glucose utilization (CMRglc) during transient or brief functional activations, but when used to study visual stimulation and seizures in other laboratories, it underestimated CMRglc. The metabolic fate of [6-14C]glucose during functional activation of cerebral metabolism is not known, and increased labeling of diffusible metabolites might explain underestimation of CMRglc and also reveal trafficking of metabolites. In the current studies cerebral cortex in conscious rats was unilaterally activated metabolically by KCl application, and CMRglc was determined in activated and contralateral control cortex with [6-14C]glucose or 2-[14C]deoxyglucose ([14C]DG) over a 5- to 7-min interval. Local 14C concentrations were determined by quantitative autoradiography. Labeled precursor and products were measured bilaterally in paired cortical samples from funnel-frozen brains. Left-right differences in 14C contents were small with [6-14C]glucose but strikingly obvious in [14C]DG autoradiographs. CMRglc determined with [6-14C]glucose was slightly increased in activated cortex but 40–80% below values obtained with [14C]DG. [14C]Lactate was a major metabolite of [6-14C]glucose in activated but not control cortex and increased proportionately with unlabeled lactate. These results demonstrate significant loss of labeled products of [6-14C]glucose from metabolically activated brain tissue and indicate that [14C]DG is the preferred tracer even during brief functional activations of brain.

Section: Labeling Of Metabolites By [ 14 C]glucosesupporting

confidence: 47%

Labeling of Metabolic Pools by [6-¹⁴C]Glucose during K⁺-Induced Stimulation of Glucose Utilization in Rat Brain

Adachi

Cruz

Sokoloff

et al. 1995

“…Hawkins et al in 1979 found up of 25%. Hawkins et al in 1985 suggested that no loss of label occurred with [6-14C]glucose through 5 min, while we found up to 10% loss at 6 min. Al though the cause of these disagreements cannot be certainly known, the ability of the double tracer technique used in this study to detect smaller dif ferences than can be detected with paired single tracer studies is almost certainly a contributing factor.…”

Section: Discussionmentioning

confidence: 45%

Comparison of Cerebral Glucose Metabolic Rates Measured with Fluorodeoxyglucose and Glucose Labeled in the 1, 2, 3–4, and 6 Positions Using Double Label Quantitative Digital Autoradiography

Lear

Ackermann

1988

Summary:We compared local cerebral glucose meta bolic rates (LCMR g 1u) that were determined with [ 18 FJfluorodeoxyglucose (FDG) and [ 14 C]glucose labeled in the 1, 2, 3-4, and 6 positions. Double label digital auto radiography was used with published kinetic models to determine LCMR gl u for FDG and glucose in the same an imals. Glucose showed metabolic rate dependent under estimation of LCMR gl u compared to FDG, which wors ened with increasing experimental times. The least un derestimation occurred with glucose labeled in the 6 Kinetic models have been proposed for the mea surement of local cerebral metabolic rate of glucose (LCMRg1u) with both radiolabeled glucose (Hawkins et aI., 1979; Lu et aI., 1983; Hawkins et aI., 1985) and glucose analogs such as deoxyglu cose (DG) (Sokoloff et aI., 1977) and fluorodeoxy glucose (FDG) (Reivich et aI., 1979; Phelps et aI., 1979;Miller and Kiney, 1981; Lear et aI., 1984; Olds et aI., 1985; Sako et aI., 1985; Lear and Ack ermann, 1988). DG and FDG cross the blood-brain barrier using the same facilitated transport system as glucose. In the brain, DG and FDG are phosphorylated by hexokinase to DG-6-phosphate (DGP) and FDG 6-phosphate (FDGP), as glucose is metabolized to Received December 22, 1987; accepted March 22, 1988. Address correspondence and reprint requests to Dr. J. L.Lear, at Nuclear Medicine (A034) , University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, CO 80262 U.S.A.Abbreviations used: DO, deoxyglucose; DOP, deoxyglucose 6-phosphate; FDO, fluorodeoxyglucose; FDOP, fluorodeoxyglu cose 6-phosphate; LCMR gt u, local cerebral glucose metabolic rates. 575position at 6 min, reaching 10% in areas of high metabo lism. Labeling in the I position, the 2 position and the 3-4 position caused progressively worse underestimation at all times. In addition, some structures showed differ ences not directly related to metabolic rate, indicating re gional variations in relationships between individual ki netic constants of FDG and glucose. Key Words: Deoxy glucose-Fluorodeoxyglucose-Glucose-Autoradiog raphy -LCMR gl u-Metabolism. glucose 6-phosphate. Unlike glucose 6-phosphate, however, further metabolism of DGP and FDGP is extremely slow; therefore DGP and FDGP accu mulate within brain cells at a rate proportional to metabolism. Thus over time, the radio tracer in the brain will change from predominantly precusor (DG or FDG) to predominantly metabolic product (DGP or FDGP). DG and FDG generally are allowed to circulate for approximately 45 min, so that by the end of the experiment the majority of the radioac tivity in the brain is DGP or FDGP. This is impor tant because neither position emission tomography scanning nor autoradiography can differentiate be tween unmetabolized DG or FDG and the com pound of interest, DGP or FDGP. After estimation of the fraction of total brain activity which is DGP or FDGP, a "lumped constant" is then used to re late cerebral DGP or FDGP concentration to glu cose metabolism. This lumped constant represents the steady-st...

“…Knudsen et al (1991) reported a value of 0.08 ± 0.03 J.Lmol min -I g-I (n = 18) for the uni directional influx of lactate in humans, which cor responds to a contribution of 10 ± 3% to the carbon flux into the TCA cycle. The pentose phosphate shunt causes label dilution by cleavage of the 13C isotope from [1-I3C]glucose and is reported to op erate at 1-3% of CMRg1 in the rat brain (Gaitonde et al, 1983;Hawkins et al, 1985), which, for our re sults, means a dilution rate of 0.0037-0.0111 J.Lmol min -I g-I.…”

Section: Sources Of Isotopic Dilutionmentioning

confidence: 53%

Simultaneous Determination of the Rates of the TCA Cycle, Glucose Utilization, α-Ketoglutarate/Glutamate Exchange, and Glutamine Synthesis in Human Brain by NMR

Mason

Gruetter

Rothman

et al. 1995

300

315

Summary: 13C isotopic tracer data previously obtained by 13C nuclear magnetic resonance in the human brain in vivo were analyzed using a mathematical model to deter mine metabolic rates in a region of the human neocortex. The tricarboxylic acid (TCA) cycle rate was 0.73 ± 0.19 fLmol min -I g-I (mean ± SD; n = 4). The standard deviation reflects primarily intersubject variation, since individual uncertainties were low. The rate of a-ketoglu tarate/glutamate exchange was 57 ± 26 fLmol min -1 g -1 (n = 3), which is much greater than the TCA cycle rate; the high rate indicates that a-ketoglutarate and glutamate are in rapid exchange and can be treated as a single com bined kinetic pool. The rate of synthesis of glutamine from glutamate was 0.47 fLmol min -I g-I (n = 4), withThe stable isotope 13C combined with nuclear magnetic resonance (NMR) spectroscopy allows