title: Preliminary research on 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol as a novel brain hypoxia PET tracer in a rodent model of stroke.
abstract: The synthesis of the new radiotracer precursor 4-Br-NITTP and the radiolabeling of the new tracer 1-(4-bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol (4-Br-[(18)F]FMISO) is reported. The cyclic voltammetry behaviour, neuronal cell toxicity, transport through the brain endothelial cell monolayer, in vivo PET imaging and preliminary calculations of the tracer uptake for a rodent model of stroke were studied for the new compound and the results were compared to those obtained with [(18)F]FMISO, the current gold standard PET hypoxia tracer. The new PET brain hypoxia tracer is more easily reduced, has higher CLogP than [(18)F]FMISO and it diffuses more rapidly through brain endothelial cells. The new compound is non-toxic to neuronal cells and it allows the in vivo mapping of stroke in mice with higher sensitivity. 4-Br-[(18)F]FMISO is a good candidate for further development in ischemic stroke.
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.
authors.forename: Elena
authors.initials: E
authors.lastname: Nieto
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain.
authors.forename: Mercedes
authors.initials: M
authors.lastname: Delgado
authors.affiliation: Unidad de Investigación Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Avenida Complutense s/n, 28040 Madrid, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Sobrado
authors.affiliation: Departamento de Neurobiología Molecular, Celular y del Desarrollo, Instituto Cajal, Avda. Doctor Arce, 37, Madrid 28002, Spain.
authors.forename: María L
authors.initials: ML
authors.lastname: de Ceballos
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain.
authors.forename: Ramón
authors.initials: R
authors.lastname: Alajarín
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain.
authors.forename: Luis
authors.initials: L
authors.lastname: García-García
authors.affiliation: Instituto Tecnológico PET, Calle Manuel Bartolomé Cossío, 10, Madrid 28040, Spain.
authors.forename: James
authors.initials: J
authors.lastname: Kelly
authors.affiliation: Unidad de Investigación Neurovascular, Departamento de Farmacología, Facultad de Medicina, Universidad Complutense, Avenida Complutense s/n, 28040 Madrid, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Lizasoain
authors.affiliation: CAI Cartografía Cerebral, Instituto Pluridisciplinar UCM, Paseo Juan XXIII, 1, Madrid 28040, Spain; Instituto Tecnológico PET, Calle Manuel Bartolomé Cossío, 10, Madrid 28040, Spain.
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Pozo
authors.affiliation: Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, 28871-Alcalá de Henares, Madrid, Spain. Electronic address: julio.alvarez@uah.es.
authors.forename: Julio
authors.initials: J
authors.lastname: Álvarez-Builla
mesh_terms: D000818:Animals; D002460:Cell Line; D004195:Disease Models, Animal; D002534:Hypoxia, Brain / Q000000981:diagnostic imaging*; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography / Q000379:methods*; D020005:Propanols / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics*; D051381:Rats; D011916:Rats, Inbred F344; D020521:Stroke / Q000000981:diagnostic imaging*
chemical_list: C000607744:1-(4-bromo-2-nitroimidazol-1-yl)-3-fluoropropan-2-ol; D009593:Nitroimidazoles; D020005:Propanols
keywords: 1-(4-Bromo-2-nitroimidazol-1-yl)-3-[(18)F]fluoropropan-2-ol; Fluorine-18; Hypoxia; Nitroimidazole; PET imaging; Stroke