Distribution of glutathione and technetium-99m-meso-HMPAO in normal and diethyl maleate-treated mouse brain mitochondria.
The aim of this study was to explain the contribution of mitochondria to the accumulation of 99mTc-meso-hexamethyl propyleneamine oxime (HMPAO) in the brain, after examinations were performed.


METHODS
We studied subcellular distribution of 99mTc-meso-HMPAO and glutathione (GSH) in normal and diethyl maleate (DEM)-administered mice.


RESULTS
In normal brain, major radioactivity was found in the mitochondrial (49.0%) and cytosolic fractions (33.0%), while the GSH content was high in the cytosol (63.2%) and mitochondria (30.6%). The radioactivity in mitochondrial, cytosolic, microsomal and nuclear fractions was decreased in a dose-dependent manner by DEM, a GSH depleting agent, to 32.2% (mitochondrial) and 24.7% (cytosolic) of the control by a dose of 550 mg/kg. The GSH content in mitochondrial and cytosolic fractions also decreased in a dose-dependent manner on DEM treatment to 29.3% (mitochondrial) and 30.0% (cytosolic) of the control by 550 mg/kg of DEM. A good correlation was found between the uptake of 99mTc-meso-HMPAO and GSH content in mitochondrial, cytosolic and nuclear fractions, with a correlation coefficient (r) of 0.814, 0.834 and 0.784, respectively.


CONCLUSIONS
Mitochondria are a major subcellular fraction for the uptake of 99mTc-meso-HMPAO by the brain, and GSH in mitochondria contributes to the accumulation of 99mTc-meso-HMPAO.
Sasaki
T
T
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Fujibayashi
Y
Y
Senda
M
M
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003600:Cytosol / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007700:Kinetics; D008298:Maleates / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D008861:Microsomes / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D019690:Technetium Tc 99m Exametazime / Q000493:pharmacokinetics*; D014018:Tissue Distribution
D008298:Maleates; D019690:Technetium Tc 99m Exametazime; C014476:diethyl maleate; D005978:Glutathione