Abstract
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Objectives Acetylcholinesterase (AChE) is an important cholinergic factor for the diagnosis of Alzheimer’s disease. We reported that 2-[F-18]fluoro-CP-118,954 ([F-18]1) has high and specific uptake in the striatum of mouse brains whereas 4-[F-18]fluorodonepezil has uniform regional distribution in mouse brains. In the present study, [F-18]1 was synthesized using a TracerLab FXFN and evaluated as a potential PET radioligand for in vivo mapping of AChE using a microPET.
Methods Automated synthesis of [F-18]1 was carried out by F-18 labeling of 2-formyl-N,N,N-trimethylanilinium triflate with K[F-18]F, followed by reductive alkylation with CP-144,885 (DMSO, 130 oC, 15 min). Manual synthesis of [F-18]1 was carried out under the same conditions as above, except using MeOH for reductive alkylation. Dynamic microPET images were obtained for 60 min after a tail vein injection of [F-18]1 (11.1 MBq-14.8 MBq). 4-[F-18]Fluorodonepezil was also synthesized and used as a negative control. Blocking study was carried out by injection of CP-118,954 (0.5 mg/kg) or Donepezil (0.5 mg/kg) into the mice at 30 min after [F-18]1 injection.
Results Radiochemical yields from automated and manual syntheses were 21±4% (50 min) and 30±5% (70 min), respectively. microPET images of [F-18]1 showed high radioactivity accumulation in the striatum (ROI: 5.3% ID/g at 60 min), which was consistent with tissue distribution results in mouse brains (3.6% ID/g at 60 min). On the other hand, there was no specific uptake in the striatum by 4-[F-18]fluorodonepezil. Blocking study demonstrated that the striatum uptake of [F-18]1 was completely inhibited by CP-118,954.
Conclusions microPET images of the mice injected with [F-18]1 showed high and specific uptake in the striatum. This result demonstrated that [F-18]1 may be a potent radioligand for in vivo mapping of AChE.
Research Support CP-144,885 was a generous gift from Pfizer Inc. (Groton, CT, USA)
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