ArticleBioorganic & medicinal chemistry2015
Synthesis and biological characterization of a promising F-18 PET tracer for vesicular acetylcholine transporter.
Article in Bioorganic & medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.
- Radiopharmaceuticals for PET and SPECT Imaging: A Literature Review over the Last Decade.International journal of molecular sciences · 2022Pooled it
- Cholinergic dysfunction in occupational manganese exposure.Neurotoxicology · 2025Article
- Cholinergic tone abnormalities and relationships with smoking severity in human cigarette smokers: exploratory positron emission tomography study using [Molecular psychiatry · 2025Article
- Radiation dosimetry and fasting-dependent hepatobiliary clearance of the VAChT-specific PET radioligandEJNMMI research · 2025Article
- A central role for acetylcholine in entorhinal cortex function and dysfunction with age in humans and mice.Cell reports · 2025Article
- Design, synthesis, and biological evaluation of multiple F-18 S1PR1 radiotracers in rodent and nonhuman primate.Organic & biomolecular chemistry · 2024Article
- The Benzoylpiperidine Fragment as a Privileged Structure in Medicinal Chemistry: A Comprehensive Review.Molecules (Basel, Switzerland) · 2024Review
- In vitro evaluation of PET radiotracers for imaging synaptic density, the acetylcholine transporter, AMPA-tarp-γ8 and muscarinic M4 receptors in Alzheimer's disease.American journal of nuclear medicine and molecular imaging · 2024Article
- An improved synthesis of [Journal of labelled compounds & radiopharmaceuticals · 2023Article
- Discovery of a Promising Fluorine-18 Positron Emission Tomography Radiotracer for Imaging Sphingosine-1-Phosphate Receptor 1 in the Brain.Journal of medicinal chemistry · 2023Article
- Computational modeling of PET imaging agents for vesicular acetylcholine transporter (VAChT) protein binding affinity: application of 2D-QSAR modeling and molecular docking techniques.In silico pharmacology · 2023Article
- In vitro characterization of [European journal of pharmacology · 2021Article
- Article
- The impact of dopamine DEuropean journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2020Article
- Advances in CNS PET: the state-of-the-art for new imaging targets for pathophysiology and drug development.European journal of nuclear medicine and molecular imaging · 2020Review
- Radiosynthesis and evaluation of a fluorine-18 labeled radioligand targeting vesicular acetylcholine transporter.Bioorganic & medicinal chemistry letters · 2018Article
- PET Imaging in Movement Disorders.Seminars in nuclear medicine · 2018Review
- Exploration of Sulfur-Containing Analogues for Imaging Vesicular Acetylcholine Transporter in the Brain.ChemMedChem · 2018Article
- Cholinergic imbalance in lumbar spinal cord of a rat model of multiple sclerosis.Journal of neuroimmunology · 2018Article
- Design, synthesis, and in vitro evaluation of quinolinyl analogues for α-synuclein aggregation.Bioorganic & medicinal chemistry letters · 2018Article
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11 authors at 2 institutions in 1 country.
Funding
Abstract
Nine fluorine-containing vesicular acetylcholine transporter (VAChT) inhibitors were synthesized and screened as potential PET tracers for imaging the VAChT. Compound 18a was one of the most promising carbonyl-containing benzovesamicol analogs; the minus enantiomer, (-)-18a displayed high potency (VAChT Ki=0.59 ± 0.06 nM) and high selectivity for VAChT versus σ receptors (>10,000-fold). The radiosynthesis of (-)-[(18)F]18a was accomplished by a two-step procedure with 30-40% radiochemical yield. Preliminary biodistribution studies of (-)-[(18)F]18a in adult male Sprague-Dawley rats at 5, 30, 60 and 120 min post-injection (p.i.) were promising. The total brain uptake of (-)-[(18)F]18a was 0.684%ID/g at 5 min p.i. and by 120 min p.i. slowly washed out to 0.409 %ID/g; evaluation of regional brain uptake showed stable levels of ∼0.800 %ID/g from 5 to 120 min p.i in the VAChT-enriched striatal tissue of rats, indicating the tracer had crossed the blood brain barrier and was retained in the striatum. Subsequent microPET brain imaging studies of (-)-[(18)F]18a in nonhuman primates (NHPs) showed high striatal accumulation in the NHP brain; the standardized uptake value (SUV) for striatum reached a maximum value of 5.1 at 15 min p.i. The time-activity curve for the target striatal region displayed a slow and gradual decreasing trend 15 min after injection, while clearance of the radioactivity from the cerebellar reference region was much more rapid. Pretreatment of NHPs with 0.25mg/kg of the VAChT inhibitor (-)-vesamicol resulted in a ∼90% decrease of striatal uptake compared to baseline studies. HPLC metabolite analysis of NHP plasma revealed that (-)-[(18)F]18a had a good in vivo stability. Together, these preliminary results suggest (-)-[(18)F]18a is a promising PET tracer candidate for imaging VAChT in the brain of living subjects.
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