Biological characters of [18F]O-FEt-PIB in a rat model of Alzheimer's disease using micro-PET imaging.
OBJECTIVE
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 beta-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 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%).


CONCLUSIONS
To our knowledge, this study is the first to evaluate a small molecular PET probe for the beta-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.
Zheng
Ming-Qiang
MQ
Research Center of Radiopharmaceuticals, Shanghai Institute of Applied Physics, Chinese Academy of Sciences, Shanghai 201800, China. comingzeng@yahoo.com.cn
Yin
Duan-Zhi
DZ
Zhang
Lan
L
Lei
Bei
B
Cheng
Deng-Feng
DF
Cai
Han-Cheng
HC
Han
Yan-Jiang
YJ
Wu
Ming-Xing
MX
Zhang
Hong
H
Wang
Jing
J
D000465:Algorithms; D000544:Alzheimer Disease / Q000175:diagnosis / Q000000981:diagnostic imaging* / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D019788:Fluorodeoxyglucose F18 / Q000378:metabolism; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000378:metabolism; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000000981:diagnostic imaging / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D014018:Tissue Distribution
C475519:2-(4'-(methylamino)phenyl)-6-hydroxybenzothiazole; D016229:Amyloid beta-Peptides; D000814:Aniline Compounds; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; D013844:Thiazoles; C098994:amyloid beta-protein (1-43); D019788:Fluorodeoxyglucose F18