title: Imaging dopamine receptors in humans with [11C]-(+)-PHNO: dissection of D3 signal and anatomy.
abstract: [(11)C]-(+)-PHNO is a D3 preferring PET radioligand which has recently opened the possibility of imaging D3 receptors in the human brain in vivo. This imaging tool allows characterisation of the distribution of D3 receptors in vivo and further investigation of their functional role. The specific [(11)C]-(+)-PHNO signal is a mixture of D3 and D2 components with the relative magnitude of each component determined by the regional receptor densities. An accurate and reproducible delineation of regions of interest (ROI) is therefore important for optimal analysis of human PET data. We present a set of anatomical guidelines for the delineation of D3 relevant ROIs including substantia nigra, hypothalamus, ventral pallidum/substantia innominata, ventral striatum, globus pallidus and thalamus. Delineation of these structures using this approach allowed for high intra- and inter-operator reproducibility. Subsequently we used a selective D3 antagonist to dissect the total [(11)C]-(+)-PHNO signal in each region into its D3 and D2 components and estimated the regional fraction of the D3 signal (f(PHNO)(D3)). In descending order of magnitude the following results for the f(PHNO)(D3) were obtained: hypothalamus=100%, substantia nigra=100%, ventral pallidum/substantia innominata=75%, globus pallidus=65%, thalamus=43%, ventral striatum=26% and precommissural-ventral putamen=6%. An automated approach for the delineation of these anatomical regions of interest was also developed and investigated in terms of its reproducibility and accuracy.
authors.affiliation: GlaxoSmithKline, Clinical Imaging Centre, Imperial College, London, UK.
authors.forename: Andri C
authors.initials: AC
authors.lastname: Tziortzi
authors.forename: Graham E
authors.initials: GE
authors.lastname: Searle
authors.forename: Sofia
authors.initials: S
authors.lastname: Tzimopoulou
authors.forename: Cristian
authors.initials: C
authors.lastname: Salinas
authors.forename: John D
authors.initials: JD
authors.lastname: Beaver
authors.forename: Mark
authors.initials: M
authors.lastname: Jenkinson
authors.forename: Marc
authors.initials: M
authors.lastname: Laruelle
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
mesh_terms: D001921:Brain / Q000000981:diagnostic imaging* / Q000502:physiology; D001931:Brain Mapping / Q000379:methods; D002250:Carbon Radioisotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging* / Q000502:physiology; D018491:Dopamine Agonists; D006801:Humans; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods; D011954:Receptors, Dopamine / Q000032:analysis*; D012016:Reference Values; D015203:Reproducibility of Results; D013495:Supraoptic Nucleus / Q000000981:diagnostic imaging / Q000502:physiology; D013788:Thalamus / Q000000981:diagnostic imaging / Q000502:physiology
chemical_list: D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D010078:Oxazines; D011954:Receptors, Dopamine; C042631:naxagolide