title: Estimating the effect of endogenous dopamine on baseline [(11) C]-(+)-PHNO binding in the human brain.
abstract: Endogenous dopamine (DA) levels at dopamine D2/3 receptors (D2/3 R) have been quantified in the living human brain using the agonist radiotracer [(11) C]-(+)-PHNO. As an agonist radiotracer, [(11) C]-(+)-PHNO is more sensitive to endogenous DA levels than antagonist radiotracers. We sought to determine the proportion of the variance in baseline [(11) C]-(+)-PHNO binding to D2/3 Rs which can be accounted for by variation in endogenous DA levels. This was done by computing the Pearson's coefficient for the correlation between baseline binding potential (BPND ) and the change in BPND after acute DA depletion, using previously published data. All correlations were inverse, and the proportion of the variance in baseline [(11) C]-(+)-PHNO BPND that can be accounted for by variation in endogenous DA levels across the striatal subregions ranged from 42-59%. These results indicate that lower baseline values of [(11) C]-(+)-PHNO BPND reflect greater stimulation by endogenous DA. To further validate this interpretation, we sought to examine whether these data could be used to estimate the dissociation constant (Kd) of DA at D2/3 R. In line with previous in vitro work, we estimated the in vivo Kd of DA to be around 20 nM. In summary, the agonist radiotracer [(11) C]-(+)-PHNO can detect the impact of endogenous DA levels at D2/3 R in the living human brain from a single baseline scan, and may be more sensitive to this impact than other commonly employed radiotracers.
authors.affiliation: Centre for Addiction and Mental Health, Research Imaging Centre, Toronto, Ontario, M5T 1R8, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: Department of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons, New York State Psychiatric Institute, New York.
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kegeles
authors.affiliation: Centre for Addiction and Mental Health, Research Imaging Centre, Toronto, Ontario, M5T 1R8, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.|Department of Psychiatry, University of Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: Centre for Addiction and Mental Health, Research Imaging Centre, Toronto, Ontario, M5T 1R8, Canada.|Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada.|Department of Psychiatry, University of Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: Centre for Addiction and Mental Health, Research Imaging Centre, Toronto, Ontario, M5T 1R8, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Borlido
authors.affiliation: Department of Psychiatry, Faculties of Medicine and Health Science, University of Malta, Msida, Malta.
authors.forename: David C
authors.initials: DC
authors.lastname: Mamo
authors.affiliation: Centre for Addiction and Mental Health, Research Imaging Centre, Toronto, Ontario, M5T 1R8, Canada. ariel.graff@camh.ca.|Institute of Medical Science, University of Toronto, Toronto, Ontario, M5S 1A8, Canada. ariel.graff@camh.ca.|Department of Psychiatry, University of Toronto, Ontario, M5T 1R8, Canada. ariel.graff@camh.ca.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D008297:Male; D010078:Oxazines / Q000493:pharmacokinetics*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics*; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism
chemical_list: D018491:Dopamine Agonists; D010078:Oxazines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide; D004298:Dopamine
keywords: AMPT; D2/3R; PET; [11C]-(+)-PHNO; dopamine