title: Estimating endogenous dopamine levels at D2 and D3 receptors in humans using the agonist radiotracer [(11)C]-(+)-PHNO.
abstract: Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D2/3 receptors (D2/3R) in humans in vivo. Our group has developed [(11)C]-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D3R. Thus, the use of [(11)C]-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D2/3R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D3R in extrastriatal regions such as the substantia nigra, hypothalamus, and ventral pallidum. Ten healthy participants underwent a [(11)C]-(+)-PHNO PET scan under baseline conditions and another under acute endogenous dopamine depletion achieved via oral administration of alpha-methyl-para-tyrosine (64 mg/kg). [(11)C]-(+)-PHNO binding was sensitive to acute dopamine depletion, allowing in vivo estimates of endogenous dopamine in D2R-rich regions (caudate and putamen), mixed D2/3R-rich regions (ventral striatum and globus pallidus), and extrastriatal D3R-rich regions (hypothalamus and ventral pallidum). Dopamine depletion decreased self-reported vigor, which was correlated with the reduction in dopamine levels in the globus pallidus. [(11)C]-(+)-PHNO is a suitable radiotracer for use in estimating endogenous dopamine levels at D2R and D3R in neuropsychiatric populations.
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Fernando
authors.initials: F
authors.lastname: Caravaggio
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Nakajima
authors.affiliation: Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada.
authors.forename: Carol
authors.initials: C
authors.lastname: Borlido
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada [3] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Gary
authors.initials: G
authors.lastname: Remington
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada [3] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Philip
authors.initials: P
authors.lastname: Gerretsen
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada [3] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Alan
authors.initials: A
authors.lastname: Wilson
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Menon
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Mamo
authors.affiliation: 1] Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, ON, Canada [2] Institute of Medical Science, University of Toronto, Toronto, ON, Canada [3] Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
authors.forename: Ariel
authors.initials: A
authors.lastname: Graff-Guerrero
mesh_terms: D000328:Adult; D000339:Affect / Q000187:drug effects; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology; D005260:Female; D006719:Homovanillic Acid / Q000097:blood; D006801:Humans; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000097:blood; D010078:Oxazines; D049268:Positron-Emission Tomography / Q000379:methods; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000819:agonists / Q000378:metabolism*; D019805:alpha-Methyltyrosine / Q000009:adverse effects / Q000097:blood / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D010078:Oxazines; D019275:Radiopharmaceuticals; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C042631:naxagolide; D008734:Methoxyhydroxyphenylglycol; D019805:alpha-Methyltyrosine; D004298:Dopamine; D006719:Homovanillic Acid