Positron-labeled antioxidant 6-deoxy-6-[18F]fluoro-L-ascorbic acid: increased uptake in transient global ischemic rat brain.
The in vivo uptake and distribution of 6-deoxy-6-[18F]fluoro-L-ascorbic acid (18F-DFA) were investigated in rat brains following postischemic reperfusion. Global cerebral ischemia was induced in male Wistar rats for 20 min by occlusion of four major arteries. Two time points were chosen for 18F-DFA injection to rats subjected to cerebral ischemia, at the start of recirculation and 5 days following recirculation. The rats were then killed at 2 h after tail-vein administration of 18F-DFA and tissue radioactivity concentration was determined. Increased uptake of radioactivity in particular brain regions, including the cerebral cortex, hypothalamus, and amygdala following injection of 18F-DFA, compared to the sham-operated control, was observed 5 days after reperfusion. Similar results were also obtained in in vitro experiments using brain slices. Abnormal in vivo accumulation of 45Ca, a marker of regional postischemic injury, was observed in these brain regions in tissue dissection experiments. Furthermore, metabolite analysis of nonradioactive DFA using 19F-NMR showed that DFA remained intact in the postischemic reperfusion brain. The present results indicate that 18F-DFA increasingly accumulates in damaged regions of postischemic reperfusion brain.
Yamamoto
F
F
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Shibata
S
S
Watanabe
S
S
Masuda
K
K
Maeda
M
M
D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics*; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D001921:Brain / Q000378:metabolism*; D002132:Calcium Radioisotopes; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics; D002546:Ischemic Attack, Transient / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism; D014018:Tissue Distribution
D000975:Antioxidants; D002132:Calcium Radioisotopes; D005462:Fluorine Radioisotopes; C076401:6-deoxy-6-fluoroascorbic acid; D001205:Ascorbic Acid