Evaluation of [14C]phenylacetate as a prototype tracer for the measurement of glial metabolism in the rat brain

Ito, Osamu; Hosoi, Rie; Momosaki, Sotaro; Yamamoto, Keisuke; Amitani, Misato; Yamaguchi, Masatoshi; Gee, Antony D.

doi:10.1016/j.nucmedbio.2006.08.007

Cited by 16 publications

(8 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The radiolabeling on the acyl group, however, is not considered suitable for cerebral AChE imaging according to the metabolite trapping method. If the acyl group of MP4A was radiolabeled, the [ 11 C]acetic acid generated in the blood would enter the brain and the [ 11 C]acetic acid would be metabolized by glial cells to form 11 CO 2 , which would be rapidly cleared from the brain . Consequently, radiolabeling of the acyl group on MP4A precludes the accurate measurement of AChE activity because of the deviation from the favorable kinetic model.…”

Section: Design Of [11c]mp4a and [11c]mp4pmentioning

confidence: 99%

PET probes for imaging brain acetylcholinesterase

Kikuchi¹,

Okamura²,

Zhang³

et al. 2013

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

Imaging acetylcholinesterase (AChE) is valuable not only for diagnosing and understanding dementia but also for monitoring the effects of cholinesterase inhibitors used as antidementia drugs and for determining the appropriate clinical dosage of newly developed cholinesterase inhibitors. The distribution of AChE in the living brain can be imaged with two different types of radioprobes, including substrate-type and ligand-type probes. The substrate-type positron emission tomography (PET) probes, N-[(11) C]methylpiperidin-4-yl acetate ([(11) C]MP4A), and its propionate, [(11) C]MP4P, have been widely used in clinical studies of dementia, including Alzheimer's disease. [(11) C]MP4A and [(11) C]MP4P have been used to demonstrate a reduction in AChE activity in the brains of dementia patients, as well as the bioavailability of AChE inhibitors, leading to the subsequent development of the widely available (18) F-labeled derivatives of MP4A. In addition, several radiolabeled cholinesterase inhibitors have been developed as PET probes for AChE mapping in the brain. Herein, we have reviewed the development of PET probes for the imaging of AChE in the brain and described the principles of measuring AChE activity in the brain using PET with substrate-type radioprobes. A discussion of the reagents developed from substrate-type PET probes for the specific measurement of AChE activity in vitro has also been provided.

show abstract

Section: Design Of [11c]mp4a and [11c]mp4pmentioning

confidence: 99%

PET probes for imaging brain acetylcholinesterase

Kikuchi¹,

Okamura²,

Zhang³

et al. 2013

Labelled Comp Radiopharmac

View full text Add to dashboard Cite

show abstract

“…All the animal experiments were carried out with the approval of the Institutional Animal Care and Use Committee, School of Allied Health Science, Osaka University. Surgery on the rat brains and infusion of glutamate and ibotenic acid Microinjection of glutamate or ibotenic acid was carried out by the same method as previously reported [23][24][25]. The rats were anesthetized with pentobarbital (50 mg/kg, i.p.)…”

Section: Animalsmentioning

confidence: 99%

De-coupling of blood flow and metabolism in the rat brain induced by glutamate

et al. 2009

Self Cite

View full text Add to dashboard Cite

show abstract

“…Whereas MP4A is metabolized to N-methyl piperidinol and acetic acid by AChE and either can be labeled with 11 C, radiolabeling on acyl group is not suitable for AChE imaging with metabolic trapping principle. If acyl group of MP4A is labeled, the labeled acetic acid generated in the blood enters in the brain [59,60] and that would make accurate measurement of AChE activity impossible. The reactivity of AChE to the substrate depends on the distance between nitrogen atom and acyl group, the steric configurations and the acyl group itself.…”

Section: Probe Design For Measurement Of Cerebral Ache Activity With mentioning

confidence: 99%

Cerebral Acetylcholinesterase Imaging: Development of the Radioprobes

Kikuchi¹,

Okamura²,

Fukushi³

et al. 2007

CTMC

View full text Add to dashboard Cite

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.

show abstract

Evaluation of [14C]phenylacetate as a prototype tracer for the measurement of glial metabolism in the rat brain

Cited by 16 publications

References 11 publications

PET probes for imaging brain acetylcholinesterase

PET probes for imaging brain acetylcholinesterase

De-coupling of blood flow and metabolism in the rat brain induced by glutamate

Cerebral Acetylcholinesterase Imaging: Development of the Radioprobes

Contact Info

Product

Resources

About