Biological characters of [18F]O-FEt–PIB in a rat model of Alzheimer's disease using micro-PET imaging
Abstract
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.
Method: [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:
Method: [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.