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PET Measurements of Myocardial Glucose Metabolism with 1-¹¹C-Glucose and Kinetic Modeling

¹ Division of Radiological Sciences, Edward Mallinckrodt Institute of Radiology, St. Louis, Missouri; ² Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri; and ³ Department of Internal Medicine and Division of Cardiothoracic Surgery, Department of Surgery, Washington University School of Medicine, St. Louis, Missouri

Correspondence: For correspondence or reprints contact: Pilar Herrero, ME, MS, Cardiovascular Imaging Laboratory, Mallinckrodt Institute of Radiology, 510 S. Kingshighway Blvd., St. Louis, Missouri 63110. E-mail:HerreroP{at}mir.wustl.edu

The aim of this study was to investigate whether compartmental modeling of 1-¹¹C-glucose PET kinetics can be used for noninvasive measurements of myocardial glucose metabolism beyond its initial extraction. Methods: 1-¹¹C-Glucose and U-¹³C-glucose were injected simultaneously into 22 mongrel dogs under a wide range of metabolic states; this was followed by 1 h of PET data acquisition. Heart tissue samples were analyzed for ¹³C-glycogen content (nmol/g). Arterial and coronary sinus blood samples (ART/CS) were analyzed for glucose (µmol/mL), ¹¹C-glucose, ¹¹CO₂, and ¹¹C-total acidic metabolites (¹¹C-lactate [LA] + ¹¹CO₂) (counts/min/mL) and were used to calculate myocardial fractions of (a) glucose and 1-¹¹C-glucose extractions, EF(GLU) and EF(¹¹C-GLU); (b) ¹¹C-GLU and ¹¹C-LA oxidation, OF(¹¹C-GLU) and OF(¹¹C-LA); (c) ¹¹C-glycolsysis, GCF(¹¹C-GLU); and (d) ¹¹C-glycogen content, GNF(¹¹C-GLU). On the basis of these measurements, a compartmental model (M) that accounts for the contribution of exogenous ¹¹C-LA to myocardial ¹¹C activity was implemented to measure M-EF(GLU), M-GCF(GLU), M-OF(GLU), M-GNF(GLU), and the fraction of myocardial glucose stored as glycogen M-GNF(GLU)/M-EF(GLU)). Results: ART/CS data showed the following: (a) A strong correlation was found between EF(¹¹C-GLU) and EF(GLU) (r = 0.92, P < 0.0001; slope = 0.95, P = not significantly different from 1). (b) In interventions with high glucose extraction and oxidation, the contribution of OF(¹¹C-GLU) to total oxidation was higher than that of OF(¹¹C-LA) (P < 0.01). In contrast, in interventions in which glucose uptake and oxidation were inhibited, OF(¹¹C-LA) was higher than OF(¹¹C-GLU) (P < 0.05). (c) A strong correlation was found between GNF(¹¹C-GLU)/EF(GLU) and direct measurements of fractional ¹³C-glycogen content, (r = 0.96, P < 0.0001). Model-derived PET measurements of M-EF(GLU), M-GCF(GLU), and M-OF(GLU) strongly correlated with EF(GLU) (slope = 0.92, r = 0.95, P < 0.0001), GCF(¹¹C-GLU) (slope = 0.79, r = 0.97, P < 0.0001), and OF(¹¹C-GLU) (slope = 0.70, r = 0.96, P < 0.0001), respectively. M-GNF(GLU)/M-EF(GLU) strongly correlated with fractional ¹³C-content (r = 0.92, P < 0.0001). Conclusion: Under nonischemic conditions, it is feasible to measure myocardial glucose metabolism noninvasively beyond its initial extraction with PET using 1-¹¹C-glucose and a compartmental modeling approach that takes into account uptake and oxidation of secondarily labeled exogenous ¹¹C-lactate.

Key Words: myocardial glucose metabolism • 1-¹¹C-glucose • PET • kinetic modeling

COPYRIGHT © 2007 by the Society of Nuclear Medicine, Inc.

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