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

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.