Title : Cerebral acetylcholinesterase imaging: development of the radioprobes - Kikuchi_2007_Curr.Top.Med.Chem_7_1790
Author(s) : Kikuchi T , Okamura T , Fukushi K , Takahashi K , Toyohara J , Okada M , Zhang MR , Irie T
Ref : Curr Top Med Chem , 7 :1790 , 2007
Abstract :

Cerebral acetylcholinesterase (AChE) imaging is not only useful for diagnosis of dementia disorders but also for therapeutic monitoring of the effects of cholinesterase (ChE) inhibitors and for decision of the appropriate clinical dosage of newly developed ChE inhibitors. Several ChE inhibitors or the derivatives such as 1,2,3,4-tetrahydro-9-methylaminoacridine (MTHA), donepezil, physostigmine, CP126,998 and 2-fluoro-CP118,954 have been labeled with positron emitters for mapping cerebral AChE by positron emission tomography (PET). When [(11)C]MTHA or [(11)C]donepezil was injected in animals, the uptake poorly reflect the regional distribution of AChE in the brain because of high non-specific binding and/or less specific to AChE in vivo in the brain tissue. [(11)C]physostigmine, [(11)C]CP126,998 and 2-[(18)F]fluoro-CP118,954 were distributed corresponding well to the regional AChE activity in animals, and also former two probes were successfully applied to clinical PET trial. The other approach is measuring cerebral AChE activity with radiolabeled acetylcholine analogue substrates. We have developed the principle for measuring cerebral enzyme activity by PET and radiolabeled N-methylpiperidinyl esters for quantitative measurement of cerebral AChE activity. N-[(11)C]methylipiperidin-4-yl acetate (MP4A) and N-[(11)C]methylpiperidin-4-yl propionate (MP4P) have been used for clinical studies of other demented disorders including Alzheimer's disease (AD), and the probes have demonstrated not only the reduction of AChE activity in the cerebral cortex of patients with AD but also the inhibitory effects of donepezil and rivastigmine on AChE activity in the brain of AD patients. Following this succession, widely available [(18)F]-labeled derivatives of MP4A and MP4P have been developed based on the structure-activity relationships between AChE and piperidinol esters.

PubMedSearch : Kikuchi_2007_Curr.Top.Med.Chem_7_1790
PubMedID: 17979787

Related information

Substrate [11C]-PMP    [11C]-MP4A

Citations formats

Kikuchi T, Okamura T, Fukushi K, Takahashi K, Toyohara J, Okada M, Zhang MR, Irie T (2007)
Cerebral acetylcholinesterase imaging: development of the radioprobes
Curr Top Med Chem 7 :1790

Kikuchi T, Okamura T, Fukushi K, Takahashi K, Toyohara J, Okada M, Zhang MR, Irie T (2007)
Curr Top Med Chem 7 :1790