Quantification of myocardial glucose utilization by pet and 1-carbon-11-glucose

BackgroundMeasurements of the rate of myocardial glucose utilization (rMGU) play a key role in the assessment of alterations in myocardial substrate metabolism in normal and abnormal cardiac states. In this study we determined whether rMGU could be quantified by positron emission tomography (PET) and 1-carbon-11-glucose.Methods and ResultsTwenty dogs were studied with a variety of interventions including fasting (n = 5), hyperinsulinemic-euglycemic clamp at rest (n = 6), clamp and phenylephrine (n = 5), and clamp and dobutamine (n = 4). Measurements of myocardial blood flow and rMGU were made by PET with oxygen-15-water and 1-C-11-glucose, respectively. Arterial-coronary sinus sampling was performed to measure rMGU by the Fick method. Values for rMGU ranged from 50 to 2436 nmol/g/min. Myocardial 1-C-11-glucose images of high quality were obtained. There was a close and direct correlation between values for rMGU measured by PET and those measured directly (y = 0.86x + 112, r = 0.98, P < .0001). The coefficient of variation for the regional estimates of rMGU ranged from 11.3% ± 7.4% during clamp at rest to 16.3% ± 8.4% during clamp with phenylephrine.ConclusionsIt now appears possible to quantify myocardial glucose utilization by PET with 1-C-11-glucose. This method should become a valuable tool in the assessment of alterations in myocardial glucose metabolism in both normal and abnormal myocardium.

[1]  G. Brooks,et al.  Intra- and extra-cellular lactate shuttles. , 2000, Medicine and science in sports and exercise.

[2]  G. Shulman,et al.  Persistent changes in myocardial glucose metabolism in vivo during reperfusion of a limited-duration coronary occlusion. , 2000, Circulation.

[3]  H. Bøtker,et al.  Myocardial glucose uptake measured with fluorodeoxyglucose: a proposed method to account for variable lumped constants. , 1999, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[4]  J. Vanoverschelde,et al.  Glucose for the heart. , 1999, Circulation.

[5]  R. Huesman,et al.  Estimating glucose metabolism using glucose analogs and two tracer kinetic models in isolated rabbit heart. , 1998, American journal of physiology. Heart and circulatory physiology.

[6]  H. Taegtmeyer,et al.  Energy provision from glycogen, glucose, and fatty acids on adrenergic stimulation of isolated working rat hearts. , 1998, American Journal of Physiology. Heart and Circulatory Physiology.

[7]  H. Zimmer Regulation of and intervention into the oxidative pentose phosphate pathway and adenine nucleotide metabolism in the heart , 1996, Molecular and Cellular Biochemistry.

[8]  K. B. Larson,et al.  Cerebral transport and metabolism of 1‐11C‐D‐glucose during stepped hypoglycemia , 1995, Annals of neurology.

[9]  H. Taegtmeyer,et al.  Fundamental limitations of [18F]2-deoxy-2-fluoro-D-glucose for assessing myocardial glucose uptake. , 1995, Circulation.

[10]  G. Lopaschuk,et al.  Epinephrine increases ATP production in hearts by preferentially increasing glucose metabolism. , 1994, The American journal of physiology.

[11]  P. Herrero,et al.  Effects of time discrepancies between input and myocardial time-activity curves on estimates of regional myocardial perfusion with PET. , 1994, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[12]  C. Dence,et al.  Improved synthesis of 1-[11C]D-glucose. , 1993, Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine.

[13]  M. Phelps,et al.  Parametric images of myocardial metabolic rate of glucose generated from dynamic cardiac PET and 2-[18F]fluoro-2-deoxy-d-glucose studies. , 1991, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[14]  L. Widén,et al.  Positron Emission Tomographic Measurements of Cerebral Glucose Utilization Using [1-11C]D-Glucose , 1990, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[15]  S. Stone-Elander,et al.  D-[U-11C]glucose uptake and metabolism in the brain of insulin-dependent diabetic subjects. , 1990, The American journal of physiology.

[16]  P. Herrero,et al.  Quantitation of myocardial blood flow with H2 15O and positron emission tomography: assessment and error analysis of a mathematical approach. , 1989, Journal of computer assisted tomography.

[17]  M. Walsh,et al.  Noninvasive quantitation of myocardial blood flow in human subjects with oxygen-15-labeled water and positron emission tomography. , 1989, Journal of the American College of Cardiology.

[18]  M. Phelps,et al.  Simple noninvasive quantification method for measuring myocardial glucose utilization in humans employing positron emission tomography and fluorine-18 deoxyglucose. , 1989, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[19]  John E. Dennis,et al.  Numerical methods for unconstrained optimization and nonlinear equations , 1983, Prentice Hall series in computational mathematics.

[20]  M E Phelps,et al.  Estimation of rabbit myocardial metabolic rate for glucose using fluorodeoxyglucose. , 1982, The American journal of physiology.

[21]  M E Phelps,et al.  Positron tomography with deoxyglucose for estimating local myocardial glucose metabolism. , 1982, Journal of nuclear medicine : official publication, Society of Nuclear Medicine.

[22]  R. DeFronzo,et al.  Glucose clamp technique: a method for quantifying insulin secretion and resistance. , 1979, The American journal of physiology.

[23]  H Lund-Andersen,et al.  Transport of glucose from blood to brain. , 1979, Physiological reviews.

[24]  C. W. Gear,et al.  Numerical initial value problem~ in ordinary differential eqttations , 1971 .

[25]  L. Sinoway,et al.  Determination of muscle-specific glucose flux using radioactive stereoisomers and microdialysis. , 2001, American journal of physiology. Endocrinology and metabolism.

[26]  S. Stone-Elander,et al.  Cerebral glucose utilization measured by positron emission tomography. [1-11C]-D-glucose compared with [2-18F]-2-fluoro-2-deoxy-D-glucose. , 1991, Acta radiologica. Supplementum.

[27]  J R Neely,et al.  Relationship between carbohydrate and lipid metabolism and the energy balance of heart muscle. , 1974, Annual review of physiology.

[28]  M. Welch,et al.  Preparation of glucose labeled with 20-minute half-lived carbon-11. , 1971, Radiation research.

[29]  W. Sacks CEREBRAL METABOLISM OF DOUBLY LABELED GLUCOSE IN HUMANS IN VIVO. , 1965, Journal of applied physiology.

[30]  R. Bing The metabolism of the heart. , 1954, Harvey lectures.