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Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity to acute amphetamine challenge in healthy humans.
J Cereb Blood Flow Metab. 2012 Jan; 32(1):127-36.JC

Abstract

[(11)C]PHNO is a D(2)/D(3) agonist positron emission tomography radiotracer, with higher in vivo affinity for D(3) than for D(2) receptors. As [(11)C]-(+)-PHNO is an agonist, its in vivo binding is expected to be more affected by acute fluctuations in synaptic dopamine than that of antagonist radiotracers such as [(11)C]raclopride. In this study, the authors compared the effects of an oral dose of the dopamine releaser amphetamine (0.3 mg/kg) on in vivo binding of [(11)C]-(+)-PHNO and [(11)C]raclopride in healthy subjects, using a within-subjects, counterbalanced, open-label design. In the dorsal striatum, where the density of D(3) receptors is negligible and both tracers predominantly bind to D(2) receptors, the reduction of [(11)C]-(+)-PHNO binding potential (BP(ND)) was 1.5 times larger than that of [(11)C]raclopride. The gain in sensitivity associated with the agonist [(11)C]-(+)-PHNO implies that ∼65% of D(2) receptors are in the high-affinity state in vivo. In extrastriatal regions, where [(11)C]-(+)-PHNO predominantly binds to D(3) receptors, the amphetamine effect on [(11)C]-(+)-PHNO BP(ND) was even larger, consistent with the higher affinity of dopamine for D(3). This study indicates that [(11)C]-(+)-PHNO is superior to [(11)C]raclopride for studying acute fluctuations in synaptic dopamine in the human striatum. [(11)C]-(+)-PHNO also enables measurement of synaptic dopamine in D(3) regions.

Authors+Show Affiliations

GlaxoSmithKline Clinical Imaging Centre, Hammersmith Hospital, London, UK. P.Shotbolt@imperial.ac.ukNo 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 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

21878947

Citation

Shotbolt, Paul, et al. "Within-subject Comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride Sensitivity to Acute Amphetamine Challenge in Healthy Humans." Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, vol. 32, no. 1, 2012, pp. 127-36.
Shotbolt P, Tziortzi AC, Searle GE, et al. Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity to acute amphetamine challenge in healthy humans. J Cereb Blood Flow Metab. 2012;32(1):127-36.
Shotbolt, P., Tziortzi, A. C., Searle, G. E., Colasanti, A., van der Aart, J., Abanades, S., Plisson, C., Miller, S. R., Huiban, M., Beaver, J. D., Gunn, R. N., Laruelle, M., & Rabiner, E. A. (2012). Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity to acute amphetamine challenge in healthy humans. Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism, 32(1), 127-36. https://doi.org/10.1038/jcbfm.2011.115
Shotbolt P, et al. Within-subject Comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride Sensitivity to Acute Amphetamine Challenge in Healthy Humans. J Cereb Blood Flow Metab. 2012;32(1):127-36. PubMed PMID: 21878947.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Within-subject comparison of [(11)C]-(+)-PHNO and [(11)C]raclopride sensitivity to acute amphetamine challenge in healthy humans. AU - Shotbolt,Paul, AU - Tziortzi,Andri C, AU - Searle,Graham E, AU - Colasanti,Alessandro, AU - van der Aart,Jasper, AU - Abanades,Sergio, AU - Plisson,Christophe, AU - Miller,Sam R, AU - Huiban,Mickael, AU - Beaver,John D, AU - Gunn,Roger N, AU - Laruelle,Marc, AU - Rabiner,Eugenii A, Y1 - 2011/08/31/ PY - 2011/9/1/entrez PY - 2011/9/1/pubmed PY - 2012/3/1/medline SP - 127 EP - 36 JF - Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism JO - J Cereb Blood Flow Metab VL - 32 IS - 1 N2 - [(11)C]PHNO is a D(2)/D(3) agonist positron emission tomography radiotracer, with higher in vivo affinity for D(3) than for D(2) receptors. As [(11)C]-(+)-PHNO is an agonist, its in vivo binding is expected to be more affected by acute fluctuations in synaptic dopamine than that of antagonist radiotracers such as [(11)C]raclopride. In this study, the authors compared the effects of an oral dose of the dopamine releaser amphetamine (0.3 mg/kg) on in vivo binding of [(11)C]-(+)-PHNO and [(11)C]raclopride in healthy subjects, using a within-subjects, counterbalanced, open-label design. In the dorsal striatum, where the density of D(3) receptors is negligible and both tracers predominantly bind to D(2) receptors, the reduction of [(11)C]-(+)-PHNO binding potential (BP(ND)) was 1.5 times larger than that of [(11)C]raclopride. The gain in sensitivity associated with the agonist [(11)C]-(+)-PHNO implies that ∼65% of D(2) receptors are in the high-affinity state in vivo. In extrastriatal regions, where [(11)C]-(+)-PHNO predominantly binds to D(3) receptors, the amphetamine effect on [(11)C]-(+)-PHNO BP(ND) was even larger, consistent with the higher affinity of dopamine for D(3). This study indicates that [(11)C]-(+)-PHNO is superior to [(11)C]raclopride for studying acute fluctuations in synaptic dopamine in the human striatum. [(11)C]-(+)-PHNO also enables measurement of synaptic dopamine in D(3) regions. SN - 1559-7016 UR - https://www.unboundmedicine.com/medline/citation/21878947/Within_subject_comparison_of_[_11_C]__+__PHNO_and_[_11_C]raclopride_sensitivity_to_acute_amphetamine_challenge_in_healthy_humans_ L2 - https://journals.sagepub.com/doi/10.1038/jcbfm.2011.115?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -