Journal article
Kinetic characterization of hexokinase isoenzymes from glioma cells: Implications for FDG imaging of human brain tumors
Nuclear medicine and biology, Vol.28(2), pp.107-116
2001
DOI: 10.1016/S0969-8051(00)00201-8
PMID: 11295420
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 ∝ (Km
glc · Vmax
FDG)/(Km
FDG · Vmax
glc). 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.
Details
- Title: Subtitle
- Kinetic characterization of hexokinase isoenzymes from glioma cells: Implications for FDG imaging of human brain tumors
- Creators
- Mark Muzi - Imaging Research Laboratory, Department of Radiology, University of Washington School of Medicine, Seattle, Washington 98195, USAScott D Freeman - Imaging Research Laboratory, Department of Radiology, University of Washington School of Medicine, Seattle, Washington 98195, USARobert C Burrows - Imaging Research Laboratory, Department of Radiology, University of Washington School of Medicine, Seattle, Washington 98195, USARobert W Wiseman - Imaging Research Laboratory, Department of Radiology, University of Washington School of Medicine, Seattle, Washington 98195, USAJeanne M Link - Imaging Research Laboratory, Department of Radiology, University of Washington School of Medicine, Seattle, Washington 98195, USAKenneth A Krohn - Imaging Research Laboratory, Department of Radiology, University of Washington School of Medicine, Seattle, Washington 98195, USAMichael M Graham - Department of Radiology, Division of Nuclear Medicine, University of Iowa, Iowa City, Iowa 52242, USAAlexander M Spence - Department of Neurology, University of Washington School of Medicine, Seattle, Washington 98195, USA
- Resource Type
- Journal article
- Publication Details
- Nuclear medicine and biology, Vol.28(2), pp.107-116
- Publisher
- Elsevier Inc
- DOI
- 10.1016/S0969-8051(00)00201-8
- PMID
- 11295420
- ISSN
- 0969-8051
- eISSN
- 1872-9614
- Language
- English
- Date published
- 2001
- Academic Unit
- Radiology; Radiation Oncology
- Record Identifier
- 9984047723202771
Metrics
13 Record Views