TY - JOUR
T1 - Estimating endogenous dopamine levels at D 2 and D 3 receptors in humans using the agonist radiotracer 11 C-(+)-PHNO
AU - Caravaggio, Fernando
AU - Nakajima, Shinichiro
AU - Borlido, Carol
AU - Remington, Gary
AU - Gerretsen, Philip
AU - Wilson, Alan
AU - Houle, Sylvain
AU - Menon, Mahesh
AU - Mamo, David
AU - Graff-Guerrero, Ariel
N1 - Funding Information:
This study was funded by Canadian Institutes of Health Research (MOP-114989) and US National Institute of Health (RO1MH084886-01A2). Dr Nakajima reports having received grants from the Japan Society for the Promotion of Science and Inokashira Hospital Research Fund and speaker’s honoraria from GlaxoSmith Kline, Janssen Pharmaceutical, Pfizer, and Yoshitomiyakuhin within the past 3 years. Dr Graff-Guerrerro currently receives research support from the following external funding agencies: Canadian Institutes of Health Research, the US National Institute of Health, and the Mexico Instituto de Ciencia y Tecnologıa para la Capital del Conocimiento en el Distrito Federal (ICyTDF). He has also received professional services compensation from Abbott Laboratories, Gedeon-Richter Plc, and Lundbeck; grant support from Janssen; and speaker compensation from Eli Lilly. Dr Remington has received research support from the Canadian Diabetes Association, the Canadian Institutes of Health Research, Medicure, Neurocrine Biosciences, Novartis, Research Hospital Fund—Canada Foundation for Innovation, and the Schizophrenia Society of Ontario and has served as a consultant or speaker for Novartis, Laboratorios FarmacéuticosRovi, Synchroneuron, and Roche. Mr Caravaggio, Ms Carol Borlido, Dr Gerretsen, Dr Sylvain Houle, and Dr Wilson report no biomedical financial interests or potential conflicts of interest relevant to the current study.
PY - 2014/11
Y1 - 2014/11
N2 - Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D 2/3 receptors (D 2/3 R) in humans in vivo. Our group has developed 11 C-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D 3 R. Thus, the use of 11 C-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D 2/3 R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D 3 R 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 D 2 R-rich regions (caudate and putamen), mixed D 2/3 R-rich regions (ventral striatum and globus pallidus), and extrastriatal D 3 R-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 D 2 R and D 3 R in neuropsychiatric populations.
AB - Using positron emission tomography (PET) and an acute dopamine depletion challenge it is possible to estimate endogenous dopamine levels occupying dopamine D 2/3 receptors (D 2/3 R) in humans in vivo. Our group has developed 11 C-(+)-PHNO, the first agonist radiotracer with preferential in vivo affinity for D 3 R. Thus, the use of 11 C-(+)-PHNO offers the novel possibility of (i) estimating in vivo endogenous dopamine levels at D 2/3 R using an agonist radiotracer, and (ii) estimating endogenous dopamine levels at D 3 R 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 D 2 R-rich regions (caudate and putamen), mixed D 2/3 R-rich regions (ventral striatum and globus pallidus), and extrastriatal D 3 R-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 D 2 R and D 3 R in neuropsychiatric populations.
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U2 - 10.1038/npp.2014.125
DO - 10.1038/npp.2014.125
M3 - Article
C2 - 24874713
AN - SCOPUS:84936764958
SN - 0893-133X
VL - 39
SP - 2769
EP - 2776
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
IS - 12
ER -
