Technetium-99m-meso-HMPAO as a potential agent to image cerebral glutathione content

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 gamma-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.