Molecular Imaging of 7 Nicotinic Acetylcholine Receptors In Vivo: Current Status and Perspectives

Brust, Peter; Deuther‐Conrad, Winnie

doi:10.5772/23787

Cited by 10 publications

(16 citation statements)

References 160 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Abbreviations: Pu = putamen; Pr = precuneous; Pa = parietal lobe; Th = thalamus; Fr = frontal lobe; Cg = cingulate; Oc = occipital; Tp = temporal lobe; Hp = hippocampus; CN = caudate nucleus; Cb = cerebellum; CC = corpus callosum. The distribution of [ 18 F]ASEM in the human brain regions is comparable with non-human primate (see for review [34]) and human post-mortem distribution of α7-nAChR [47-48]. The brain kinetics of [ 18 F]ASEM are reversible.…”

Section: Figmentioning

confidence: 79%

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

Horti¹

2015

Biochemical Pharmacology

View full text Add to dashboard Cite

The alpha-7 subtype of the nicotinic acetylcholine receptor (α7-nAChR) is fundamental to physiology; it mediates various brain functions and represents an important target for drug discovery. Exploration of the brain nicotinic acetylcholine receptors (nAChRs) using positron-emission tomography (PET) will make it possible to better understand the important role of this receptor and to study its involvement in schizophrenia, bipolar disorder, Alzheimer's and Parkinson's diseases, drug dependence, inflammation and many other disorders and simplify the development of nicotinic drugs for treatment of these disorders. Until recently, PET imaging of α7-nAChRs has been impeded by the absence of good radiotracers. This review describes various endeavors to develop α7-nAChR PET tracers by several research groups including the author’s group. Most initial PET tracers for imaging α7-nAChRs did not exhibit suitable imaging properties due to their low specific binding. Recently discovered [18F]ASEM is the first highly specific α7-nAChR radioligand and it was recently translated to human PET imaging.

show abstract

Section: Figmentioning

confidence: 79%

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

Horti¹

2015

Biochemical Pharmacology

View full text Add to dashboard Cite

show abstract

“…Using homogenates obtained from rat cortex and rat liver, respectively, enables a comparison of binding data of the three targets considered within the same species. DTG were used as radioligands for s 1 and s 2 , respectively [45]. To block competitive binding of [ 3 H]DTG on s 1 receptor, the s 2 receptor assays were performed using 1 mM s 1 receptor-specific dextrallorphan.…”

Section: In Vitro Binding Studiesmentioning

confidence: 99%

New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure

Barthel

Sorger

Deuther‐Conrad

et al. 2015

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

“…This implies the need to search for higher target affi nity (1/K D ) if the receptor density (B max ) is low. For example, the receptor densities for α7 nAChRs in the human brain are between 2 and 16 fmol/mg tissue [96] . Accordingly, a K D between 1 and 8 nmol/L is required to fulfil the minimal criteria.…”

Section: New Compoundsmentioning

confidence: 99%

“…Overexpression of σ receptors has been found in many brain tumor cell lines and in human brain tumors [92] . The neuroprotective potential of σ 1 receptor agonists has been shown in different models of neurodegeneration [89,93] and is expected to be important for cancerous diseases as well [92,94] .As another example, impaired cholinergic neurotransmission is a key feature of AD and the related cognitive impairment is at least partially associated with loss of cortical nicotinic acetylcholine receptors (nAChRs) [6,95] .There is evidence that both subtypes with the highest expression in the brain are involved: α4β2 and α7 nAChRs.Accordingly, these subtypes have been chosen for radiotracer development [6,96,97] . However, these nAChRs are not only key proteins in neurodegenerative diseases ( Fig.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

2014

Self Cite

View full text Add to dashboard Cite

Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including geneticallyengineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.Keywords: Alzheimer's disease; autoradiography; blood-brain barrier; brain tumor; cholinergic system; kinetic modeling; metabolism; molecular imaging; neurodegeneration; positron emission tomography; precursor; psychiatric disorder; radiotracer; sigma receptor ·Review· IntroductionPositron emission tomography (PET) is an in vivo molecular imaging tool widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. Positron-emitting radionuclide-labeled substances allow the visualization, characterization, and measurement of biological processes at the molecular and cellular levels in humans and other living systems by highly sensitive coincidence-detection [1] . This is based on 511 keV photons (gamma radiation) originating from positronelectron annihilation. PET differs in that aspect from other modalities such as single-photon emission computed tomography (SPECT), magnetic resonance imaging (MRI), optical imaging, and ultrasound. Because of their high sensitivity (~10 -9 to 10 -12 M) PET and SPECT offer advantages over the other methods. Therefore, in the past, they were the only modalities that allowed noninvasive imaging of biochemical receptor sites. Nowadays, the other imaging modalities compete in that aspect although precise absolute quantitation in terms of biochemical parameters has not been achieved yet. fusion accuracy, provides an advanced diagnostic tool and research platform [2,3] .PET and SPECT use biomolecules as probes, labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. According to the concept developed by George ...

show abstract

Molecular Imaging of 7 Nicotinic Acetylcholine Receptors In Vivo: Current Status and Perspectives

Cited by 10 publications

References 160 publications

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

Development of [ 18 F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography

New systematically modified vesamicol analogs and their affinity and selectivity for the vesicular acetylcholine transporter – A critical examination of the lead structure

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

Contact Info

Product

Resources

About