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


CONCLUSIONS
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.
Sasaki
T
T
Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Japan.
Senda
M
M
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis*; D066298:In Vitro Techniques; D008298:Maleates / Q000494:pharmacology; D051379:Mice; D015609:Organotechnetium Compounds; D010091:Oximes; D011817:Rabbits; D019275:Radiopharmaceuticals; D051381:Rats; D017208:Rats, Wistar; D013438:Sulfhydryl Compounds / Q000032:analysis; D019690:Technetium Tc 99m Exametazime
D008298:Maleates; D015609:Organotechnetium Compounds; D010091:Oximes; D019275:Radiopharmaceuticals; D013438:Sulfhydryl Compounds; D019690:Technetium Tc 99m Exametazime; D019328:Buthionine Sulfoximine; C014476:diethyl maleate; D005978:Glutathione