ArticleBioorganic & medicinal chemistry2013
Radiosynthesis of N-(4-chloro-3-[(11)C]methoxyphenyl)-2-picolinamide ([(11)C]ML128) as a PET radiotracer for metabotropic glutamate receptor subtype 4 (mGlu4).
Article in Bioorganic & medicinal chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 24 citations in OpenAlex.
- Structural basis for modulation of group III mGlu receptors by transsynaptic interactions.Science advances · 2026Article
- Advances and Insights in Positron Emission Tomography Tracers for Metabotropic Glutamate Receptor 4 Imaging.Journal of medicinal chemistry · 2024Review
- Fully Automated Radiosynthesis of [iRadiology · 2023Article
- Detailed radiosynthesis of [Journal of labelled compounds & radiopharmaceuticals · 2023Article
- A hybrid approach unveils drug repurposing candidates targeting an Alzheimer pathophysiology mechanism.Patterns (New York, N.Y.) · 2022Article
- Design, Synthesis, and Characterization of Benzimidazole Derivatives as Positron Emission Tomography Imaging Ligands for Metabotropic Glutamate Receptor 2.Journal of medicinal chemistry · 2020Article
- Synthesis and Characterization of Fluorine-18-LabeledJournal of medicinal chemistry · 2020Article
- Improved Synthesis of the Thiophenol PrecursorTetrahedron · 2019Article
- Functional modulation of G-protein coupled receptors during Parkinson disease-like neurodegeneration.Neuropharmacology · 2016Article
- Synthesis and evaluation of N-(methylthiophenyl)picolinamide derivatives as PET radioligands for metabotropic glutamate receptor subtype 4.Bioorganic & medicinal chemistry letters · 2016Article
- Co-operative binding assay for the characterization of mGlu4 allosteric modulators.Neuropharmacology · 2015Article
- Re-exploring the N-phenylpicolinamide derivatives to develop mGlu4 ligands with improved affinity and in vitro microsomal stability.Bioorganic & medicinal chemistry letters · 2015Article
- Development of PET and SPECT probes for glutamate receptors.TheScientificWorldJournal · 2015Review
- Radiosynthesis and evaluation of an 18F-labeled positron emission tomography (PET) radioligand for metabotropic glutamate receptor subtype 4 (mGlu4).Journal of medicinal chemistry · 2014Article
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7 authors at 2 institutions in 1 country.
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Abstract
N-(Chloro-3-methoxyphenyl)-2-picolinamide (3, ML128, VU0361737) is an mGlu4 positive allosteric modulator (PAM), which is potent and centrally penetrating. 3 is also the first mGlu4 PAM to show efficacy in a preclinical Parkinson disease model upon systemic dosing. As a noninvasive medical imaging technique and a powerful tool in neurological research, positron emission tomography (PET) offers a possibility to investigate mGlu4 expression in vivo under physiologic and pathological conditions. We synthesized a carbon-11 labeled ML128 ([(11)C]3) as a PET radiotracer for mGlu4, and characterized its biological properties in Sprague Dawley rats. [(11)C]3 was synthesized from N-(4-chloro-3-hydroxyphenyl)-2-picolinamide (2) using [(11)C]CH3I. Total synthesis time was 38±2.2min (n=7) from the end of bombardment to the formulation. The radioligand [(11)C]3 was obtained in 27.7±5.3% (n=5) decay corrected radiochemical yield based on the radioactivity of [(11)C]CO2. The radiochemical purity of [(11)C]3 was >99%. Specific activity was 188.7±88.8GBq/mol (n=4) at the end of synthesis (EOS). PET images were conducted in 20 normal male Sprague Dawley rats including 11 control studies, 6 studies blocking with an mGlu4 modulator (4) to investigate specificity and 3 studies blocking with an mGlu5 modulator (MTEP) to investigate selectivity. These studies showed fast accumulation of [(11)C]3 (peak activity between 1-3min) in several brain areas including striatum, thalamus, hippocampus, cerebellum, and olfactory bulb following with fast washout. Blocking studies with the mGlu4 modulator 4 showed 22-28% decrease of [(11)C]3 accumulation while studies of selectivity showed only minor decrease supporting good selectivity over mGlu5. Biodistribution studies and blood analyses support fast metabolism. Altogether this is the first PET imaging ligand for mGlu4, in which the labeled ML128 was used for imaging its in vivo distribution and pharmacokinetics in brain.
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