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Characteristic Brain Distribution of 1-¹⁴C-Octanoate in a Rat Model of Focal Cerebral Ischemia in Comparison with Those of ¹²³I-IMP and ¹²³I-Iomazenil

¹ Departments of Tracer Kinetics and Nuclear Medicine, Graduate School of Medicine, Hokkaido University, Sapporo, Japan
² Faculty of Pharmaceutical Sciences, Health Science University of Hokkaido, Ishikari, Japan

1-¹¹C-Octanoate is a potential tracer for studying astroglial function in PET. To evaluate the usefulness of 1-¹¹C-octanoate for studying ischemic stroke, we investigated the brain distribution of 1-¹⁴C-octanoate and compared it with N-isopropyl-p-¹²³I-iodoamphetamine (¹²³I-IMP) distribution (cerebral blood flow), ¹²³I-iomazenil (¹²³I-IMZ) distribution (neuronal viability based on ¹²³I-IMZ binding to benzodiazepine receptors), and hematoxylin-eosin stain (morphologic changes) in a rat model of focal cerebral ischemia. Methods: The right middle cerebral artery of each rat was occluded intraluminally. The brain distribution of 1-¹⁴C-octanoate and ¹²³I-IMP (or ¹²³I-IMZ) was determined 4 and 24 h after the insult using a dual-tracer autoradiographic technique (n = 4–7 in each group). Coronal brain sections adjacent to those used for autoradiography were stained with hematoxylin and eosin. Regions of interest (ROIs) were determined for 3 coronal slices, and asymmetry indices (AIs, lesion/normal hemisphere) of the tracer uptake were calculated. ROIs on the hemisphere with the lesion were classified into 4 groups: In region A, widespread necrotic cells were observed; in region B, necrotic cells were occasionally observed; in region C1, no morphologic changes were observed and the AIs for ¹²³I-IMP (or ¹²³I-IMZ) were 0.8; and in region C2, no morphologic changes were observed and the AIs for ¹²³I-IMP (or ¹²³I-IMZ) were >0.8. Results: 1-¹⁴C-Octanoate uptake decreased in the regions where morphologic changes were observed (regions A and B) but was relatively preserved in the surrounding region without morphologic changes despite reduced ¹²³I-IMP and ¹²³I-IMZ uptake (region C1). In the region without morphologic changes (region C1), AIs for 1-¹⁴C-octanoate were significantly higher than those for ¹²³I-IMP (4 h, 0.73 ± 0.23 for 1-¹⁴C-octanoate and 0.37 ± 0.20 for ¹²³I-IMP, P < 0.0001; 24 h, 0.84 ± 0.11 for 1-¹⁴C-octanoate and 0.44 ± 0.15 for ¹²³I-IMP, P < 0.0001) and those for ¹²³I-IMZ (4 h, 0.83 ± 0.19 for 1-¹⁴C-octanoate and 0.57 ± 0.13 for ¹²³I-IMZ, P < 0.0001; 24 h, 0.91 ± 0.13 for 1-¹⁴C-octanoate and 0.73 ± 0.06 for ¹²³I-IMZ, P < 0.0001). Conclusion: 1-¹⁴C-Octanoate uptake was relatively preserved in the regions without morphologic changes despite reduced ¹²³I-IMP and ¹²³I-IMZ uptake. 1-¹¹C-Octanoate may provide further functional information on the pathophysiology of ischemic stroke, reflecting astroglial function based on fatty acid metabolism.

Key Words: 1-¹¹C-octanoate • cerebral ischemia • glial function • neuronal function • cerebral blood flow

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