Hyperfixation of copper-62-PTSM in rat brain after transient global ischemia.

Abstract

We evaluated the regional distribution of 62Cu-pyruvaldehyde bis(N4-methylthiosemicarbazone) (62Cu-PTSM), a potential PET perfusion agent, in the rat brain and observed hyperfixation in transient global ischemia in rats. The distribution of 62Cu-PTSM was examined in comparison with that of 123I-labeled p-iodophenyl-N-isopropylmethanphetamine (123I-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. Copper-62-PTSM showed accelerated accumulation in the brain at 1 hr and 1 day after reperfusion when compared with that of 123I-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). Copper-62-PTSM showed hyperfixation most possibly as a result of increased NADH concentration, caused by disturbed electron transport in mitochondria.