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Evaluation of Glutathione Localization in Brain Using ^99mTc meso-HMPAO

Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan

Correspondence: For correspondence or reprints contact: Toru Sasaki, PhD, Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabasahi, Tokyo 173-0022, Japan.

ABSTRACT

The relationship between distribution of ^99mTc meso-hexamethyl propyleneamine oxime (HMPAO) and glutathione (GSH) content was studied in the mouse. Methods: The regional distributions of ^99mTc meso-HMPAO and ^99mTc d, I-HMPAO were examined using tissue sampling and autoradiographic methods and were compared with GSH content and distribution by a histochemical procedure. Results: The uptake of ^99mTc meso-HMPAO was highest in the cerebellum and lowest in the brain stem, whereas the distribution of ^99mTc_,I-HMPAO was more uniform. The regional distribution of ^99mTc meso-HMPAO in the mouse brain correlated with GSH content (r = 0.787), but that of ^99mTc d_,I-HMPAO did not. Treatment with diethyl maleate, a GSH depletor, significantly decreased the ^99mTm meso-HMPAO uptake to 21%–33% of the control in every region, but the reduction of the ^99mTc d_,I-HMPAO uptake was moderate (58%–65% of the control). In the autoradiograph, the radioactivity of ^99mTc meso-HMPAO was higher in the gray matter than in the white matter of cerebellum, and more radioactivity was found in cerebellum and in hippocampus than in forebrain without the hippocampus. This pattern of distribution was similar to the histochemical localization of GSH estimated with a sulfhydryl reagent, Mercury orange. Conclusion: ^99mTc meso-HMPAO might be used as an imaging agent to assess GSH localization in the brain.

Key Words: regional distribution • ^99mTc meso-hexamethyl propyleneamine oxime • glutathione • brain • histochemical evaluation