Kinetic characterization of hexokinase isoenzymes from glioma cells: Implications for FDG imaging of human brain tumors

Mark Muzi, Scott D. Freeman, Robert C. Burrows, Robert W. Wiseman, Jeanne M. Link, Kenneth A. Krohn, Michael M. Graham, Alexander M. Spence

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

Quantitative imaging of glucose metabolism of human brain tumors with PET utilizes 2-[18F]-fluorodeoxy-D-glucose (FDG) and a conversion factor called the lumped constant (LC), which relates the metabolic rate of FDG to glucose. Since tumors have greater uptake of FDG than would be predicted by the metabolism of native glucose, the characteristic of tumors that governs the uptake of FDG must be part of the LC. The LC is chiefly determined by the phosphorylation ratio (PR), which is comprised of the kinetic parameters (Km and Vmax) of hexokinase (HK) for glucose as well as for FDG (LC ∝ (Kmglc · VmaxFDG)/(KmFDG · Vmaxglc). The value of the LC has been estimated from imaging studies, but not validated in vitro from HK kinetic parameters. In this study we measured the kinetic constants of bovine and 36B-10 rat glioma HK I (predominant in normal brain) and 36B-10 glioma HK II (increased in brain tumors) for the hexose substrates glucose, 2-deoxy-D-glucose (2DG) and FDG. Our principal results show that the KmGlc < KmFDG ≪ Km2DG and that PR2DG < PRFDG. The FDG LC calculated from our kinetic parameters for normal brain, possessing predominantly HK I, would be higher than the normal brain LC predicted from animal studies using 2DG or human PET studies using FDG or 2DG. These results also suggest that a shift from HK I to HK II, which has been observed to increase in brain tumors, would have little effect on the value of the tumor LC.

Original languageEnglish (US)
Pages (from-to)107-116
Number of pages10
JournalNuclear Medicine and Biology
Volume28
Issue number2
DOIs
StatePublished - Jan 1 2001

Keywords

  • 2-Deoxyglucose
  • Glioma
  • Glucose
  • Hexokinase
  • Lumped Constant
  • Positron emission tomography
  • [F]Fluorodeoxyglucose

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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