title: MRI sensing of neurotransmitters with a crown ether appended Gd(3+) complex.
abstract: Molecular magnetic resonance imaging (MRI) approaches that detect biomarkers associated with neural activity would allow more direct observation of brain function than current functional MRI based on blood-oxygen-level-dependent contrast. Our objective was to create a synthetic molecular platform with appropriate recognition moieties for zwitterionic neurotransmitters that generate an MR signal change upon neurotransmitter binding. The gadolinium complex (GdL) we report offers ditopic binding for zwitterionic amino acid neurotransmitters, via interactions (i) between the positively charged and coordinatively unsaturated metal center and the carboxylate function and (ii) between a triazacrown ether and the amine group of the neurotransmitters. GdL discriminates zwitterionic neurotransmitters from monoamines. Neurotransmitter binding leads to a remarkable relaxivity change, related to a decrease in hydration number. GdL was successfully used to monitor neural activity in ex vivo mouse brain slices by MRI.
authors.affiliation: Centre de Biophysique Moléculaire, CNRS , rue Charles Sadron, 45071 Orléans, Cedex 2, France.
authors.forename: Fatima
authors.initials: F
authors.lastname: Oukhatar
authors.forename: Sandra
authors.initials: S
authors.lastname: Même
authors.forename: William
authors.initials: W
authors.lastname: Même
authors.forename: Frédéric
authors.initials: F
authors.lastname: Szeremeta
authors.forename: Nikos K
authors.initials: NK
authors.lastname: Logothetis
authors.forename: Goran
authors.initials: G
authors.lastname: Angelovski
authors.forename: Éva
authors.initials: É
authors.lastname: Tóth
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002491:Central Nervous System Agents / Q000494:pharmacology; D003287:Contrast Media / Q000138:chemical synthesis / Q000737:chemistry; D043844:Crown Ethers / Q000138:chemical synthesis / Q000737:chemistry; D005260:Female; D005682:Gadolinium / Q000737:chemistry; D021621:Imaging, Three-Dimensional / Q000379:methods; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D066244:Proton Magnetic Resonance Spectroscopy; D046509:Tissue Culture Techniques
chemical_list: D002491:Central Nervous System Agents; D003287:Contrast Media; D043844:Crown Ethers; D018377:Neurotransmitter Agents; D011189:Potassium Chloride; D005682:Gadolinium
keywords: Crown ether; MRI; gadolinium; neurotransmitter sensing; responsive agent