Assessment of antioxidative ability in brain: Imaging of glutathione localization with technetium-99M meso-hexamethyl propyleneamine oxime
- Positron Medical Center, Tokyo (Japan); and others
An oxidative stress is postulated to be important in tissue injury after ischemia and reperfusion, inflammation, aging and various disease. Glutathione (GSH), one of the major antioxidants in the brain, is presumed to be responsible for the metabolism and retention of [Tc-99m] HM-PAO. In order to visualize the regional localization of GSH in the brain, the relationship between the concentrations of tissue GSH and uptake of [Tc-99m] meso-HM-PAO and [Tc-99m] d,l-HM-PAO was studied in mice. Increasing load of diethyl maleate (DEM), a reducing agent of GSH and several other thiols, before [Tc-99m] meso-HM-PAO injection, led to a dose dependent decrease of GSH and [Tc-99m] meso-HM-PAO. At the highest dose of loaded DEM, the uptake of [Tc-99m] meso-HM-PAO in the brain was decreased to 20-30% of the control. In contrast, pretreatment with DEM did little affect the [Tc-99m] d,l-HM-PAO uptake. To elucidate the retention mechanism of [Tc-99m] HM-PAO in brain, we studied the in vitro interactions of [Tc-99m] meso-HMPAO and [Tc-99m] d,l-HM-PAO with GSH, ascorbate and cysteine by measuring octanol-extractable radioactivity, which is remaining intact [Tc-99m] HM-PAO, as a function of incubation period. The disappearance raw of [Tc-99m] meso-HMPAO and [TC-99m] d,l-HM-PAO were 0.18 and 0.96%/min, respectively. Either meso or d,l-isomer did not interact with ascorbate or cysteine. This result suggested that the retention mechanism of [Tc-99m] meso- and d,l-isomers in brain was related to their specific interaction with GSH, and did not related to non-specific interaction with various thiols or other reducing agents. This extremely high reaction rate of [Tc-99m] d,l-HM-PAO with GSH could explain the capability of a small amount of GSH to trap [Tc-99m] d,l-HM-PAO in maximum DEM loading. These results indicated that [Tc-99m] meso-HMPAO would be suitable to image the concentration of GSH in the brain, as opposed d,l-isomer that images blood flow.
- OSTI ID:
- 198111
- Report Number(s):
- CONF-940605-; ISSN 0161-5505; TRN: 95:007029-0264
- Journal Information:
- Journal of Nuclear Medicine, Vol. 35, Issue Suppl.5; Conference: 41. annual meeting of the Society of Nuclear Medicine, Orlando, FL (United States), 5-8 Jun 1994; Other Information: PBD: May 1994
- Country of Publication:
- United States
- Language:
- English
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