PMID- 11295420
OWN - NLM
STAT- MEDLINE
DCOM- 20010726
LR  - 20190921
IS  - 0969-8051 (Print)
IS  - 0969-8051 (Linking)
VI  - 28
IP  - 2
DP  - 2001 Feb
TI  - Kinetic characterization of hexokinase isoenzymes from glioma cells: implications 
      for FDG imaging of human brain tumors.
PG  - 107-16
AB  - Quantitative imaging of glucose metabolism of human brain tumors with PET 
      utilizes 2-[(18)F]-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 proportional to (Km(glc) x 
      Vmax(FDG))/(Km(FDG) x 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.
FAU - Muzi, M
AU  - Muzi M
AD  - Imaging Research Laboratory, Department of Radiology, University of Washington 
      School of Medicine, Seattle, Washington 98195, USA. muzi@u.washington.edu
FAU - Freeman, S D
AU  - Freeman SD
FAU - Burrows, R C
AU  - Burrows RC
FAU - Wiseman, R W
AU  - Wiseman RW
FAU - Link, J M
AU  - Link JM
FAU - Krohn, K A
AU  - Krohn KA
FAU - Graham, M M
AU  - Graham MM
FAU - Spence, A M
AU  - Spence AM
LA  - eng
GR  - P01 CA042045/CA/NCI NIH HHS/United States
GR  - P01-CA42045-14/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Nucl Med Biol
JT  - Nuclear medicine and biology
JID - 9304420
RN  - 0 (Isoenzymes)
RN  - 0 (Radiopharmaceuticals)
RN  - 0Z5B2CJX4D (Fluorodeoxyglucose F18)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Animals
MH  - Brain Neoplasms/*diagnostic imaging/*enzymology
MH  - Cattle
MH  - *Fluorodeoxyglucose F18/pharmacokinetics
MH  - Glioma/*enzymology
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Isoenzymes/metabolism
MH  - Kinetics
MH  - Radiopharmaceuticals/pharmacokinetics
MH  - Rats
MH  - Rats, Inbred F344
MH  - Tomography, Emission-Computed
MH  - Tumor Cells, Cultured
EDAT- 2001/04/11 10:00
MHDA- 2001/07/28 10:01
CRDT- 2001/04/11 10:00
PHST- 2001/04/11 10:00 [pubmed]
PHST- 2001/07/28 10:01 [medline]
PHST- 2001/04/11 10:00 [entrez]
AID - S0969-8051(00)00201-8 [pii]
AID - 10.1016/s0969-8051(00)00201-8 [doi]
PST - ppublish
SO  - Nucl Med Biol. 2001 Feb;28(2):107-16. doi: 10.1016/s0969-8051(00)00201-8.