title: Quantification of [(11)C]yohimbine binding to α2 adrenoceptors in rat brain in vivo.
abstract: We quantified the binding potentials (BPND) of [(11)C]yohimbine binding in rat brain to alpha-2 adrenoceptors to evaluate [(11)C]yohimbine as an in vivo marker of noradrenergic neurotransmission and to examine its sensitivity to the level of noradrenaline. Dual [(11)C]yohimbine dynamic positron emission tomography (PET) recordings were applied to five Sprague Dawley rats at baseline, followed by acute amphetamine administration (2 mg/kg) to induce elevation of the endogenous level of noradrenaline. The volume of distribution (VT) of [(11)C]yohimbine was obtained using Logan plot with arterial plasma input. Because alpha-2 adrenoceptors are distributed throughout the brain, the estimation of the BPND is complicated by the absence of an anatomic region of no displaceable binding. We used the Inhibition plot to acquire the reference volume, VND, from which we calculated the BPND. Acute pharmacological challenge with amphetamine induced a significant decline of [(11)C]yohimbine BPND of ~38% in all volumes of interest. The BPND was greatest in the thalamus and striatum, followed in descending order by, frontal cortex, pons, and cerebellum. The experimental data demonstrate that [(11)C]yohimbine binding is sensitive to a challenge known to increase the extracellular level of noradrenaline, which can benefit future PET investigations of pathologic conditions related to disrupted noradrenergic neurotransmission.
authors.affiliation: 1] Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark [2] Department of Biomedicine, Aarhus University, Aarhus, Denmark.
authors.forename: Jenny-Ann
authors.initials: JA
authors.lastname: Phan
authors.affiliation: 1] Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark [2] Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark.
authors.forename: Anne M
authors.initials: AM
authors.lastname: Landau
authors.affiliation: 1] Department of Radiology and Radiological Science, Division of Nuclear Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [2] Department of Psychiatry, Neuroscience and Environmental Health Sciences, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA [3] Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Dean F
authors.initials: DF
authors.lastname: Wong
authors.affiliation: Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Jakobsen
authors.affiliation: 1] Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark [2] Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Adjmal
authors.initials: A
authors.lastname: Nahimi
authors.affiliation: 1] Department of Nuclear Medicine and PET Centre, Aarhus University Hospital, Aarhus, Denmark [2] Department of Medicine/Neurology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
authors.affiliation: 1] Center of Functionally Integrative Neuroscience, Aarhus University, Aarhus, Denmark [2] Department of Radiology and Radiological Science, Division of Nuclear Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA [3] Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark [4] Department of Neurology, McGill University, Montreal, Quebec, Canada.
authors.forename: Albert
authors.initials: A
authors.lastname: Gjedde
mesh_terms: D000818:Animals; D001921:Brain / Q000000981:diagnostic imaging*; D002250:Carbon Radioisotopes; D032068:Pausinystalia / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism
chemical_list: D002250:Carbon Radioisotopes; D019275:Radiopharmaceuticals; D018341:Receptors, Adrenergic, alpha-2