Evaluation of PET ligands (+)N‐[11C]ethyl‐3‐piperidyl benzilate and (+)N‐[11C]propyl‐3‐piperidyl benzilate for muscarinic cholinergic receptors: A PET study with microdialysis in comparison with (+)N‐[11C]methyl‐3‐piperidyl benzilate in the conscious monkey brain

  title={Evaluation of PET ligands (+)N‐[11C]ethyl‐3‐piperidyl benzilate and (+)N‐[11C]propyl‐3‐piperidyl benzilate for muscarinic cholinergic receptors: A PET study with microdialysis in comparison with (+)N‐[11C]methyl‐3‐piperidyl benzilate in the conscious monkey brain},
  author={S. Nishiyama and Hideo Tsukada and K. Sato and T. Kakiuchi and Hiroyuki Ohba and Norihiro Harada and K. Takahashi},
We developed PET ligands (+)N‐[11C]ethyl‐3‐piperidyl benzilate ([11C](+)3‐EPB) and (+)N‐[11C]propyl‐3‐piperidyl benzilate ([11C](+)3‐PPB) for cerebral muscarinic cholinergic receptors. The distribution and kinetics of the novel ligands were evaluated for comparison with the previously reported ligand (+)N‐[11C]methyl‐3‐piperidyl benzilate ([11C](+)3‐MPB) in the monkey brain (Macaca mulatta) in the conscious state using high‐resolution positron emission tomography (PET). At 60–91 min… 
(R)‐N‐[11C]methyl‐3‐pyrrolidyl benzilate, a high‐affinity reversible radioligand for PET studies of the muscarinic acetylcholine receptor
This compound displayed high, receptor‐mediated retention in regions of the mouse and rat brain known to have high concentrations of mAChRs, and bolus studies in a pigtail monkey showed that this compound had superior clearance from the brain when compared to muscarinic radiotracers previously employed in human PET studies.
Potential of [18F]β‐CFT‐FE (2β‐carbomethoxy‐3β‐(4‐fluorophenyl)‐8‐(2‐[18F]fluoroethyl)nortropane) as a dopamine transporter ligand: A PET study in the conscious monkey brain
Results suggested that [18F]β‐CFT‐FE could be a potential imaging agent for DAT, providing excellent selectivity and tracer kinetics for quantitative PET imaging.
Age differences in muscarinic cholinergic receptors assayed with (+)N‐[11C]methyl‐3‐piperidyl benzilate in the brains of conscious monkeys
The usefulness of kinetic three‐compartment model analysis of [11C](+)3‐MPB with metabolite‐corrected arterial plasma input as an indicator for the aging process of the cortical muscarinic cholinergic receptors in vivo as measured by PET is demonstrated.
Validation of reference tissue model of PET ligand [11C](+)3‐MPB for the muscarinic cholinergic receptor in the living brain of conscious monkey
It is suggested that the cerebellum is a suitable reference region for quantification of mAChR in the living brain with [11C](+)3‐MPB and PET.
Synthesis of [1‐11C]propyl and [1‐11C]butyl iodide from [11C]carbon monoxide and their use in alkylation reactions
Compounds labelled with 11C (β+, t1/2 = 20.4 min) are used in positron emission tomography (PET), which is a quantitative non-invasive molecular imaging technique. It utilizes computerized
PET Imaging of Muscarinic Receptors
We have successfully developed a novel PET ligand for muscarinic acetylcholine receptors (mAChR), (+)N-[11C]methyl-3-piperidyl benzilate ([11C](+)3-MPB), and evaluated this in the brain of conscious
Imaging of Muscarinic Receptors in the Central Nervous System
It is demonstrated that PET imaging with 11C-(+)3-MPB could be useful for diagnosis of neurological diseases associated with impaired mAChR function and cognitive function.
Discovery of a Novel Muscarinic Receptor PET Radioligand with Rapid Kinetics in the Monkey Brain.
(S,R)-[11C]1 is a promising candidate for measuring changes in endogenous acetylcholine concentrations and was designed and synthesized via N-11C-methylation at high radiochemical purity and high specific radioactivity.
Effects of aging on 5‐HT1A receptors and their functional response to 5‐HT1a agonist in the living brain: PET study with [carbonyl‐11C]WAY‐100635 in conscious monkeys
The usefulness of [carbonyl‐11C]WAY‐100635 as an indicator of the age-related changes in cortical 5‐HT1A receptors measured noninvasively by PET was demonstrated and suggested that the age‐related impairment of 5‐ HT1A receptor responses to 8‐OH‐DPAT might be related to the reduced efficacy of antidepressant therapy in elderly patients with depression.


Evaluation of novel PET ligands (+)N‐[11C]methyl‐3‐piperidyl benzilate ([11C](+)3‐MPB) and its stereoisomer [11C](‐)3‐MPB for muscarinic cholinergic receptors in the conscious monkey brain: A PET study in comparison with [11C]4‐MPB
The in vivo binding parameters as well as uptake at 60–91 min postinjection of [11C](+)3‐MPB were consistent with muscarinic receptor density in the brain as reported in vitro.
Synthesis and autoradiographic localization of muscarinic cholinergic antagonist (+)N-[11C]methyl-3-piperidyl benzilate as a potent radioligand for positron emission tomography.
Synthesis, rodent biodistribution, dosimetry, metabolism, and monkey images of carbon-11-labeled (+)-2 alpha-tropanyl benzilate: a central muscarinic receptor imaging agent.
The results represent intermediate steps in the development of [11C]TRB for quantification of central muscarinic receptors in man and show highly specific and saturable binding of [ 11C] TRB in the striatum and cortex.
Mapping muscarinic receptors in human and baboon brain using [N‐11C‐methyl]‐benztropine
Data combined with postmortem studies in humans and primates demonstrate that [N‐11C‐methyl]‐benztropine is a suitablemuscarinic cholinergic ligand for use in human and baboon brain and high resolution positron emission tomography (PET).
Distinct kinetic binding propeties of N‐[3H]‐methylscopolamine afford differential labeling and localization of M1, M2, and M3 muscarinic receptor subtypes in primate brain
The conditions for selective occupancy of the M1, M2, and M3 receptor sub types in the brain of the rhesus monkey were based on the distinct kinetic and equilibrium binding properties of N‐[3H]‐methylscopolamine (NMS) at cloned m1–m4 muscarinic receptor subtypes expressed in A9L transfected cells.
Ketamine decreased striatal [11C]raclopride binding with no alterations in static dopamine concentrations in the striatal extracellular fluid in the monkey brain: Multiparametric PET studies combined with microdialysis analysis
The results suggest that the inhibition of glutamatergic neuronal activity modulates dopamine turnover in the striatum by simultaneous enhancement of the dynamics of dopamine synthesis and DAT availability to the same extent, resulting in no apparent changes in ECF dopamine concentration as measured by microdialysis.
Quantification of Muscarinic Cholinergic Receptors with [11C]NMPB and Positron Emission Tomography: Method Development and Differentiation of Tracer Delivery from Receptor Binding
The authors conclude that pixel-by-pixel-weighted integral analyses of NMPB distribution introduce transport biases into receptor-binding estimates, and similar confounding effects also are predicted in noncompartmental analyses of delayed radiotracer distribution.
Age‐related decreases in muscarinic cholinergic receptor binding in the human brain measured with positron emission tomography (PET)
It is suggested that regions high in muscarinic receptor density, the corpus striatum and the cortical mantle, show a greater rate of decline than those areas that have a relatively low number ofMuscarinic receptors.