title: Quantitative assessment of glucose transport in human skeletal muscle: dynamic positron emission tomography imaging of [O-methyl-11C]3-O-methyl-D-glucose.
abstract: 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 ([(18)F]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 [(11)C]3-O-methylglucose ([(11)C]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.m(2). Dynamic PET imaging of calf muscles was conducted for 90 min after the injection of [(11)C]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 [(18)F]FDG, a two-compartment model was applied. Consistent with prior [(18)F]FDG findings, insulin was found to have minimal effect on the rate constant for movement of [(11)C]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 [(11)C]3-OMG increased 6-fold compared with basal conditions. We conclude that dynamic PET imaging of [(11)C]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.
authors.affiliation: Montefiore-University Hospital, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoldo
authors.forename: Julie
authors.initials: J
authors.lastname: Price
authors.forename: Chet
authors.initials: C
authors.lastname: Mathis
authors.forename: Scott
authors.initials: S
authors.lastname: Mason
authors.forename: Daniel
authors.initials: D
authors.lastname: Holt
authors.forename: Carol
authors.initials: C
authors.lastname: Kelley
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
authors.forename: David E
authors.initials: DE
authors.lastname: Kelley
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006151:Guanosine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D008954:Models, Biological; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*
chemical_list: D002250:Carbon Radioisotopes; D009004:Monosaccharide Transport Proteins; C037626:3'-O-methylguanosine; D006151:Guanosine; D005947:Glucose