ArticleNuclear medicine and biology2013
Synthesis and evaluation of new radioligands [(11)C]A-833834 and [(11)C]A-752274 for positron-emission tomography of α7-nicotinic acetylcholine receptors.
Article in Nuclear medicine and biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed.
- Human brain imaging of α7 nAChR with [(18)F]ASEM: a new PET radiotracer for neuropsychiatry and determination of drug occupancy.Molecular imaging and biology · 2014Trial
- Advances in PET Imaging of α7 Nicotinic Receptors: From Radioligand Development to CNS Applications.Basic & clinical pharmacology & toxicology · 2025Review
- Imaging Cholinergic Receptors in the Brain by Positron Emission Tomography.Journal of medicinal chemistry · 2023Review
- The role of astrocytic α7 nicotinic acetylcholine receptors in Alzheimer disease.Nature reviews. Neurology · 2023Review
- Failed PET Application Attempts in the Past, Can We Avoid Them in the Future?Molecular imaging and biology · 2016Article
- Selected PET Radioligands for Ion Channel Linked Neuroreceptor Imaging: Focus on GABA, NMDA and nACh Receptors.Current topics in medicinal chemistry · 2016Review
- Development of [(18)F]ASEM, a specific radiotracer for quantification of the α7-nAChR with positron-emission tomography.Biochemical pharmacology · 2015Review
- PET Imaging of the Human Nicotinic Cholinergic Pathway in Atherosclerosis.Current cardiology reports · 2015Review
- 18F-ASEM, a radiolabeled antagonist for imaging the α7-nicotinic acetylcholine receptor with PET.Journal of nuclear medicine : official publication, Society of Nuclear Medicine · 2014Article
- Evaluating the role of the alpha-7 nicotinic acetylcholine receptor in the pathophysiology and treatment of schizophrenia.Biochemical pharmacology · 2013Review
- Derivatives of dibenzothiophene for positron emission tomography imaging of α7-nicotinic acetylcholine receptors.Journal of medicinal chemistry · 2013Article
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Abstract
introductionα7-nicotinic acetylcholine receptor (α7-nAChR) is one of the major neuronal nAChR subtypes. α7-nAChR is involved in variety of neuronal processes and disorders including schizophrenia and Alzheimer's disease. A number of α7-nAChR PET radioligands have been developed, but a quality radiotracer remains to be discovered.
methodsHigh binding affinity α7-nAChR ligands A-833834 and A-752274 were radiolabeled with (11)C. Baseline and blockade biodistribution studies in the mouse brain of [(11)C]A-833834 (5-(6-(5-[(11)C]methylhexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)pyridazin-3-yl)-1H-indole) and [(11)C]A-752274 (2-(6-[(11)C]methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)-7-(6-methyl-3,6-diazabicyclo[3.2.0]heptan-3-yl)-9H-fluoren-9-one) were performed. [(11)C]A-752274 was evaluated in a baseline baboon PET study.
results[(11)C]A-833834 and [(11)C]A-752274 were synthesized by radiomethylation of corresponding des-methyl precursors. The radioligands were prepared with radiochemical yield of 12%-32%, high specific radioactivity (330-403GBq/μmol) and radiochemical purity>95%. Dissection studies with [(11)C]A-833834 demonstrated low specific α7-nAChR binding in the mouse brain. [(11)C]A-752274 specifically (~50%) labeled α7-nAChR in the mouse thalamus. However, [(11)CA-752274 exhibited low brain uptake in baboon (%SUV<100).
conclusionTwo novel α7-nAChR ligands radioligands were synthesized and studied in animals. Specific binding of [(11)C]A-833834 in the mouse brain is low due to the insufficient binding affinity of the radioligand. The very high binding affinity [(11)C]A-752274 exhibited good specific binding in the α7-nAChR-rich mouse brain regions. The low uptake of [(11)C]A-752274 in the baboon brain is due to its high hydrophilicity, rapid metabolism or other properties. Future development of α7-nAChR PET radioligands will be based on compounds with high binding affinities and good blood-brain barrier permeability.
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