Acta Pharmacologica Sinica 2008 May; 29 (5): 548-554; doi: 10.1111/j.1745-7254.2008.00785.x

Aim: To evaluate whether the newly-synthesized positron emission tomography (PET) tracer, [¹⁸F]2-(4'-(methylamino)phenyl)-6-fluoroethoxy- benzothiazole ([¹⁸F]O-FEt-PIB), could bind to β-amyloid aggregates in a rat model of Alzheimer's disease (AD) using micro-PET.

Methods: [¹⁸F]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 [¹⁸F]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 [¹⁸F]2-Deoxy-2-fluoro-D-glucose ([¹⁸F]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 [¹⁸F]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 β-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 β-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 β-amyloid plaques in AD.

Keywords: emicro-positron emission tomography; [¹⁸F]O-FEt-PIB; Alzheimer's disease