HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Sasaki, T. Articles by Senda, M. Search for Related Content PubMed PubMed Citation Articles by Sasaki, T. Articles by Senda, M.

Technetium-99m-meso-HMPAO as a Potential Agent to Image Cerebral Glutathione Content

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, Itabashi, Tokyo, Japan.

ABSTRACT

To clarify whether the content of glutathione (GSH) in the brain can be estimated by the uptake of ^99mTc-meso-HMPAO, we conducted the following in vivo and in vitro experiments. Methods: We investigated the effect of diethyl maleate (DEM) and buthionine sulfoximine (BSO) administration on the brain uptake of ^99mTc-meso-HMPAO in the mouse, rat and rabbit, and the chemical specificity of in vitro interaction of ^99mTc-HMPAO to GSH using measurements of octanol-extractable radioactivity as an index of remaining intact tracer. Results: The uptake of ^99mTc-meso-HMPAO in the mouse and rat brain were reduced together with decreased content of GSH by preloading of DEM, a GSH depletor that acts through glutathione S-transferase. Neither ^99mTc-meso-HMPAO uptake nor GSH content was affected in the rabbit brain.Similarly,the uptake of ^99mTc-meso-HMPAO and GSH content in the mouse brain was reduced by preinjection of BSO, a GSH depletor that acts through -glutamylcysteine synthetase. In an in vitro study, ^99mTc-HMPAO showed reactivity to the molecules possessing a -SH group, but were not specific to GSH. The order of ^99mTc-meso-HMPAO reactivity to the mouse brain homogenate agreed with the order of GSH concentration: normal > BSO > DEM. GSH was a major contributor to the conversion reaction of ^99mTc-meso-HMPAO to hydrophilic complex in mouse brain homogenate. Conclusion: GSH may have a major responsibility for trapping ^99mTc-HMPAO in the brain, suggesting the possibility of in vivo measurement of brain GSH with ^99mTc-meso-HMPAO.

Key Words: glutathione • localization • technetium-99m-meso-hexa-methyl propyleneamine oxime • brain