In vivo measurement of brain glucose transport and metabolism employing glucose- -11C

Abstract

The radiopharmaceutical glucose--11C was used in vivo measurement of brain-glucose transport kinetics and metabolism in the rhesus monkey. Radiotracer was injected intravenously as a bolus. Radioactivity was continuously recorded from the head and from the arterial blood via an indwelling peripheral artery catheter for a collectionperiod of 2-3 min. To correct the reading obtained from the head for radioactivitycontained in blood, a second intravenous injection of the vascular tracer -15O-labeled carboxyhemoglobin was used. The method was tested in nine phencyclidine-anesthetized monkeys in which cerebral glucose metabolism (CMRGlc) was simultaneously measured by our method and by a standard method emplying the Fick principle. A highlysignificant correlation was found between the two methods of measuring CMRGlc (r =0.929). In addition, our model predicted a ratio of forward-to-reverse glucose flux across the blood-brain barrier (BBR) (1.37 plus or minus 0.23 SD), the brain-to-bloodglucose concentration ratio across the BBB (0.633 plus or minus 0.14), the relative tissue free-glucose space (17 plus or minus 7%), the brain free-glucose concentration (13.6plus or minus 8.5 mg/100 g of tissue), and the brain free-glucose turnover time (2.96 plus or minus 1.98 min). author

In vivo1H‐[13C]‐NMR spectroscopy of cerebral metabolism

“…In subsequent steps of the TCA cycle the carbon skeleton originating from glucose is completely oxidized to form six molecules of carbon dioxide. In the process, the hydrogen carriers NAD þ and FAD are reduced to NADH and FADH 2 and carry hydrogen to the respiratory chain on the inner mitochondrial membrane. Adenosine triphosphate (ATP) is formed by the coupled processes of electron transport and oxidative phosphorylation in which electrons from NADH and FADH 2 are donated to molecular oxygen, which is subsequently reduced to water.…”

“…It is well known that under normal conditions the oxidation of glucose is the primary mechanism for cerebral energy production. 1 The methods of autoradiography 2,3 and positron emission tomography 4,5 (PET) have been used to assess regional glucose uptake in animal and human brain, respectively, by measuring the distribution of radioactivity following infusion of isotopically labeled glucose or glucose analogues, 2-deoxy-D-glucose (DG) and 2-fluoro-2-deoxy-Dglucose (FDG). The information provided by glucose analogs is limited as they may not accurately reflect glucose metabolism and cannot provide flux information through metabolic pathways, like glycolysis.…”

“…Previous in vivo 13 C NMR spectroscopy in combination with intravenous [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose infusion has shown abundant labeling of [4][5][6][7][8][9][10][11][12][13] C]-glutamate and [4][5][6][7][8][9][10][11][12][13] C]-glutamine, both in animal 6,7 and human [8][9][10][11] brain. These experiments, in combination with previous knowledge on compartmentalized glutamate metabolism, 12,13 allowed the development of a quantitative, mathematical model of glucose metabolism.…”

“…C labeling of substrate molecules, like [1][2][3][4][5][6][7][8][9][10][11][12][13] C]-glucose, in combination with dynamic 13 C NMR spectroscopy is a unique tool to study the metabolic pathways involved in cerebral energy production and neurotransmission non-invasively in vivo. Figure 1 shows a schematic diagram following the flow of 13 [4-13 C]-glutamate by the exchange reactions of amino acid transaminases and mitochondrial/ cytosolic transporters.…”

Factors which affect cerebral uptake and retention of 13NH3.

“…The values of the cerebral metabolic rate for glucose (CMRGlu) and oxygen (CMRO 2 ) were calculated using a standard Fick technique as discussed in detail elsewhere. 20 Experimental Procedures…”