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Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans.
Hum Brain Mapp. 2008 Apr; 29(4):400-10.HB

Abstract

The D(2) receptors exist in either the high- or low-affinity state with respect to agonists, and while agonists bind preferentially to the high-affinity state, antagonists do not distinguish between the two states. [(11)C]-(+)-PHNO is a PET D(2) agonist radioligand and therefore provides a preferential measure of the D(2) (high) receptors. In contrast, [(11)C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D(2) high- and low-affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [(11)C]-(+)-PHNO and [(11)C]raclopride in volunteers using a within-subject design. Both radioligands accumulated in brain areas rich in D(2)/D(3)-receptors. However, [(11)C]-(+)-PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [(11)C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [(11)C]raclopride, equal in the ventral-striatum (3.4 vs. 3.3), and higher in the globus pallidus for [(11)C]-(+)-PHNO (1.8 vs. 3.3). Moreover [(11)C]-(+)-PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [(11)C]-(+)-PHNO in the globus pallidus and ventral-striatum could be the presence of a greater proportion of high- vs. low-affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D(3)-over-D(2) with [(11)C]-(+)-PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease.

Authors+Show Affiliations

PET Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17497628

Citation

Graff-Guerrero, Ariel, et al. "Brain Region Binding of the D2/3 Agonist [11C]-(+)-PHNO and the D2/3 Antagonist [11C]raclopride in Healthy Humans." Human Brain Mapping, vol. 29, no. 4, 2008, pp. 400-10.
Graff-Guerrero A, Willeit M, Ginovart N, et al. Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans. Hum Brain Mapp. 2008;29(4):400-10.
Graff-Guerrero, A., Willeit, M., Ginovart, N., Mamo, D., Mizrahi, R., Rusjan, P., Vitcu, I., Seeman, P., Wilson, A. A., & Kapur, S. (2008). Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans. Human Brain Mapping, 29(4), 400-10.
Graff-Guerrero A, et al. Brain Region Binding of the D2/3 Agonist [11C]-(+)-PHNO and the D2/3 Antagonist [11C]raclopride in Healthy Humans. Hum Brain Mapp. 2008;29(4):400-10. PubMed PMID: 17497628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans. AU - Graff-Guerrero,Ariel, AU - Willeit,Matthaeus, AU - Ginovart,Nathalie, AU - Mamo,David, AU - Mizrahi,Romina, AU - Rusjan,Pablo, AU - Vitcu,Irina, AU - Seeman,Philip, AU - Wilson,Alan A, AU - Kapur,Shitij, PY - 2007/5/15/pubmed PY - 2008/7/1/medline PY - 2007/5/15/entrez SP - 400 EP - 10 JF - Human brain mapping JO - Hum Brain Mapp VL - 29 IS - 4 N2 - The D(2) receptors exist in either the high- or low-affinity state with respect to agonists, and while agonists bind preferentially to the high-affinity state, antagonists do not distinguish between the two states. [(11)C]-(+)-PHNO is a PET D(2) agonist radioligand and therefore provides a preferential measure of the D(2) (high) receptors. In contrast, [(11)C]raclopride is an antagonist radioligand and thus binds with equal affinity to the D(2) high- and low-affinity states. The aim was to compare the brain uptake, distribution and binding characteristics between [(11)C]-(+)-PHNO and [(11)C]raclopride in volunteers using a within-subject design. Both radioligands accumulated in brain areas rich in D(2)/D(3)-receptors. However, [(11)C]-(+)-PHNO showed preferential uptake in the ventral striatum and globus pallidus, while [(11)C]raclopride showed preferential uptake in the dorsal striatum. Mean binding potentials were higher in the putamen (4.3 vs. 2.8) and caudate (3.4 vs 2.1) for [(11)C]raclopride, equal in the ventral-striatum (3.4 vs. 3.3), and higher in the globus pallidus for [(11)C]-(+)-PHNO (1.8 vs. 3.3). Moreover [(11)C]-(+)-PHNO kinetics in the globus pallidus showed a slower washout than other regions. One explanation for the preferential binding of [(11)C]-(+)-PHNO in the globus pallidus and ventral-striatum could be the presence of a greater proportion of high- vs. low-affinity receptors in these areas. Alternatively, the observed distribution could also be explained by a preferential binding of D(3)-over-D(2) with [(11)C]-(+)-PHNO. This differential binding of agonist vs. antagonist radioligand, especially in the critically important region of the limbic striatum/pallidum, offers new avenues to investigate the role of the dopamine system in health and disease. SN - 1065-9471 UR - https://www.unboundmedicine.com/medline/citation/17497628/Brain_region_binding_of_the_D2/3_agonist_[11C]__+__PHNO_and_the_D2/3_antagonist_[11C]raclopride_in_healthy_humans_ L2 - https://doi.org/10.1002/hbm.20392 DB - PRIME DP - Unbound Medicine ER -