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Hyperfixation of Copper-62-PTSM in Rat Brain After Transient Global Ischemia

Faculty of Pharmaceutical Sciences and Faculty of Medicine, Kyoto University, Kyoto; Biomedical Imaging Research Center, Fukui Medical School, Fukui, Japan

Correspondence: For correspondence and reprints contact: Yasuhisa Fujibayashi, PhD, D Med Sci, Department of Genetic Biochemistry, Faculty of Pharmaceutical Sciences, Kyoto University, Shimoadachi-cho, Yoshida, Sakyo-ku, Kyoto, 606, Japan.

ABSTRACT

We evaluated the regional distribution of ⁶²Cu-pyruvaldehyde bisi(N⁴-methylthiosemicarbazone)(⁶²Cu-PTSM), a potential PET perfusion agent, in the rat brain and observed hyperfixation in transient global ischemia in rats. Methods: The distribution of ⁶²Cu-PTSM was examined in comparison with that of ¹³¹I-labeled p-iodophenyl-N-isopropylmethanphetamine (¹³¹I-IMP) as a reference blood flow marker. Brain uptake of these two tracers was measured in Wistar rats subjected to 30-min four-vessel occlusion followed by recirculation for 10 min, 1 hr or 1, 3 or 5 days. Tracers were injected intravenously into rats 10 min before decapitation. The activities of Complex I and Complex I–III of mitochondria and the concentration of sulfhydryl (SH) groups were also measured. Results: Copper-62-PTSM showed accelerated accumulation in the brain at 1 hr and 1 day after reperfusion when compared with that of ¹³¹I-IMP(p < 0.01), and this enhancement was considered to be due to hyperfixation. At these time points, SH concentration was significantly decreased (p < 0.01). On the other hand, the activity of Complex I was not influenced by ischemia/reperfusion, but that of Complex I–III was decreased to 65–70% of the control level (p < 0.01). Conclusion: Copper-62-PTSM showed hyperfixation most possibly as a result of increased NADH concentration, caused by disturbed electron transport in mitochondria.

Key Words: hyperfixation • cerebral ischemia • reperfusion injury • copper-62

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