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Quantitative Assessment of Glucose Transport in Human Skeletal Muscle: Dynamic Positron Emission Tomography Imaging of [O-Methyl-¹¹C]3-O-Methyl-D-Glucose

Departments of Medicine (C.K., D.E.K.) and Radiology (J.P., C.M., S.M., D.H.), University of Pittsburgh, Pittsburgh, Pennsylvania 15213; and Department of Information Engineering, University of Padova (A.B., C.C.), Padova 35121, Italy

Address all correspondence and requests for reprints to: Dr. David E. Kelley, 807N Montefiore-University Hospital, 3459 Fifth Avenue, Pittsburgh, Pennsylvania 15213. E-mail: kelley{at}msx.dept-med.pitt.edu.

Insulin-stimulated glucose transport in skeletal muscle is regarded as a key determinant of insulin sensitivity, yet isolation of this step for quantification in human studies is a methodological challenge. One notable approach is physiological modeling of dynamic positron emission tomography (PET) imaging using 2-[18-fluoro]2-deoxyglucose ([¹⁸F]FDG); however, this has a potential limitation in that deoxyglucose undergoes phosphorylation subsequent to transport, complicating separate estimations of these steps. In the current study we explored the use of dynamic PET imaging of [¹¹C]3-O-methylglucose ([¹¹C]3-OMG), a glucose analog that is limited to bidirectional glucose transport. Seventeen lean healthy volunteers with normal insulin sensitivity participated; eight had imaging during basal conditions, and nine had imaging during euglycemic insulin infusion at 30 mU/min·m². Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [¹¹C]3-OMG. Spectral analysis of tissue activity indicated that a model configuration of two reversible compartments gave the strongest statistical fit to the kinetic pattern. Accordingly, and consistent with the structure of a model previously used for [¹⁸F]FDG, a two-compartment model was applied. Consistent with prior [¹⁸F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [¹¹C]3-OMG from plasma to tissue interstitium. However, during insulin infusion, a robust and highly significant increase was observed in the kinetics of inward glucose transport; this and the estimated tissue distribution volume for [¹¹C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [¹¹C]3-OMG offers a novel quantitative approach that is both chemically specific and tissue specific for in vivo assessment of glucose transport in human skeletal muscle.

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