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PET Imaging of Neuroinflammation Using [11C]DPA-713 in a Mouse Model of Ischemic Stroke
Published on: June 14, 2018
Longitudinal observation of [11C]4DST uptake in turpentine-induced inflammatory tissue
Jun Toyohara1, Muneyuki Sakata, Keiichi Oda
1Research Team for Neuroimaging, Tokyo Metropolitan Institute of Gerontology, 1-1 Naka-cho, Itabashi-ku, Tokyo 173-0022, Japan. toyohara@pet.tmig.or.jp
Introduction:
Longitudinal changes of 4'-[methyl-(11)C]thiothymidine ([(11)C]4DST) uptake were evaluated in turpentine-induced inflammation.
Methods:
Turpentine (0.1 ml) was injected intramuscularly into the right hind leg of male Wistar rats. Longitudinal [(11)C]4DST uptake was evaluated by the tissue dissection method at 1, 2, 4, 7, and 14 days after turpentine injection (n=5). The tumor selectivity index was calculated using the previously published biodistribution data in C6 glioma-bearing rats. Dynamic PET scan was performed on day 4 when maximum [(11)C]4DST uptake was observed during the longitudinal study. Histopathological analysis and Ki-67 immunostaining were also performed.
Results:
The uptake of [(11)C]4DST in inflammatory tissue was significantly increased on days 2-4 after turpentine injection, and then decreased. On day 14, tracer uptake returned to the day 1 level. The maximum SUV of inflamed muscle was 0.6 and was 3 times higher than that of the contralateral healthy muscle on days 2-4 after turpentine injection. However, tumor selectivity index remains very high (>10) because of the low inflammation uptake. A dynamic PET scan showed that the radioactivity in inflammatory tissues peaked at 5 min after [(11)C]4DST injection, and then washed out until 20 min. At intervals >20 min, radioactivity levels were constant and double that of healthy muscle. The changes in Ki-67 index were paralleled with those of [(11)C]4DST uptake, indicating cell proliferation-dependent uptake of [(11)C]4DST in inflammatory tissues.
Conclusion:
In our animal model, low but significant levels of [(11)C]4DST uptake were observed in subacute inflammation.
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