Intracellular metabolism of 99mTc-d, l-HMPAO in vitro : A basic approach for understanding the hyperfixation mechanism in damaged brain

• Published in: Nuclear medicine and biology Vol. 25; no. 4; pp. 375 - 378
• Main Authors: FUJIBAYASHI, Y, TANIUCHI, H, WAKI, A, YOKOYAMA, A, ISHII, Y, YONEKURA, Y
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier 01.05.1998
• Subjects: Animals; Biological and medical sciences; Brain Injuries - metabolism; Cells, Cultured; Cytosol - drug effects; Cytosol - metabolism; Hot Temperature; Male; Medical sciences; Mice; Nervous system involvement in other diseases. Miscellaneous; Neurology; Sodium Dodecyl Sulfate - pharmacology; Submitochondrial Particles - drug effects; Submitochondrial Particles - metabolism; Surface-Active Agents - pharmacology; Technetium Tc 99m Exametazime - metabolism; Redox state; Nervous system diseases; Thiol; Radiolabelling; Rat; Rodentia; Binding site; Technetium; Metabolism; In vitro; Cerebral disorder; Vertebrata; Mitochondria; Mammalia; Animal; Central nervous system disease; Reaction mechanism; Diagnosis; Intracellular
• ISSN: 0969-8051; 1872-9614
• DOI: 10.1016/s0969-8051(97)00221-7

The mechanism of technetium-99m-labeled d,l-hexamethylpropylene amine oxime (99mTc-HMPAO) hyperfixation in damaged brain was elucidated using in vitro metabolic studies. Among the subcellular fractions of mouse brain homogenate, the mitochondrial fraction showed dominant metabolic activity with respect to 99mTc-HMPAO, followed by the cytosolic fraction. The metabolic activity of the mitochondrial fraction was enhanced by heat and detergent treatment, being proportional to the leakage of thiol (SH) compound(s) from the granules. The leaked SH compound(s) had a higher metabolic activity than glutathione, a well-known reductant in cells. 99mTc-HMPAO might be metabolized by mitochondrial SH compound(s) exhibiting strong reductant activity, and hyperfixation might be an indication of mitochondrial damage of the brain.