Journal
ACTA PHARMACOLOGICA SINICA
Volume 29, Issue 5, Pages 548-554Publisher
NATURE PUBL GROUP
DOI: 10.1111/j.1745-7254.2008.00785.x
Keywords
micro-positron emission tomography; [F-18]O-FEt-PIB; Alzheimer's disease
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Aim: To evaluate whether the newly-synthesized positron emission tomography (PET) tracer, [F-18]2-(4'-(methylamino)phenyl)-6-fluoroethoxy- benzothiazole ([F-18] O-FEt-PIB), could bind to beta-amyloid aggregates in a rat model of Alzheimer's disease (AD) using micro-PET. Method: [F-18]O-FEt-PIB was synthesized and purified by radio HPLC. PET imaging was performed with a R4 rodent model scanner in 3 model and 3 control rats. Dynamic PET scans were performed for 40 min in each rat following an injection of approximately 37 MBq of [F-18]O-FEt-PIB. Static scans were also performed for 15 min in each rat. PET data were reconstructed by a maximum posteriori probability algorithm. On the coronal PET images, regions of interest were respectively placed on the cortex, hemicerebrum [including the hippocampus and thalamus (HT)], and were guided by a 3-D digital map of the rat brain or the brain images of [F-18]2-Deoxy-2-fluoro-JD-glucose ([F-18]FDG) in normal rats. Time-activity curves (TAC) were obtained for the cerebrum and cerebellum. The activity difference value (ADV) between 2 hemicerebrums was also calculated. Results: The TAC for [F-18]O-FEt-PIB in the cerebrum or cerebellum peaked early (at approximately 2 min), but washed out a little slowly. In the dynamic and static micro-PET images, increased radioactivity was found in the area of the right HT in the model rats where infused with beta-amyloid (1-40). No distinct difference of radioactivity was found between the right and left HT areas in the control rats. The ADV((HT)) was approximately 14.6% in the AD model rats and approximately 4 times greater than that of the control rats (3.9%). Conclusion: To our knowledge, this study is the first to evaluate a small molecular PET probe for the p-amyloid deposits in vivo using micro-PET imaging in an AD-injected rat model. The suitable biological characters showed that the tracer had potential to be developed as a probe for detecting beta-amyloid plaques in AD.
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