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Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography.
J Neurochem. 2006 May; 97(4):1089-103.JN

Abstract

[11C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a new agonist radioligand that provides a unique opportunity to measure the high-affinity states of the D2 receptors (D2-high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of [11C]-(+)-PHNO and compare it with the well characterized antagonist D2 radioligand, [11C]raclopride, in cat. [11C]-(+)-PHNO displayed high uptake in striatum with a mean striatal binding potential (BP) of 3.95 +/- 0.85. Pre-treatment with specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB-277011) antagonists indicated that [11C]-(+)-PHNO binding in striatum is specific to D2 receptors. Within-subject comparisons showed that [11C]-(+)-PHNO BP in striatum was almost 2.5-fold higher than that measured with [11C]-(-)-NPA ([11C]-(-)-N-propyl-norapomorphine). Comparison of the dose-effect of amphetamine (0.1, 0.5 and 2 mg/kg; i.v.) showed that [11C]-(+)-PHNO was more sensitive to the dopamine releasing effect of amphetamine than [11C]raclopride. Amphetamine induced up to 83 +/- 4% inhibition of [11C]-(+)-PHNO BP and only up to 56 +/- 8% inhibition of [11C]raclopride BP. Scatchard analyses of [11C]-(+)-PHNO and [11C]raclopride bindings in two cats showed that the Bmax obtained with the agonist (29.6 and 32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL). The high penetration of [11C]-(+)-PHNO in brain, its high signal-to-noise ratio, its favorable in vivo kinetics and its high sensitivity to amphetamine shows that [11C]-(+)-PHNO has highly suitable characteristics for probing the D2-high with PET.

Authors+Show Affiliations

The Vivian Rakoff Positron Emission Tomography Unit, Center for Addiction and Mental Health, Toronto, Canada. nathalie.ginovart@camhpet.caNo 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)

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

Language

eng

PubMed ID

16606355

Citation

Ginovart, Nathalie, et al. "Binding Characteristics and Sensitivity to Endogenous Dopamine of [11C]-(+)-PHNO, a New Agonist Radiotracer for Imaging the High-affinity State of D2 Receptors in Vivo Using Positron Emission Tomography." Journal of Neurochemistry, vol. 97, no. 4, 2006, pp. 1089-103.
Ginovart N, Galineau L, Willeit M, et al. Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography. J Neurochem. 2006;97(4):1089-103.
Ginovart, N., Galineau, L., Willeit, M., Mizrahi, R., Bloomfield, P. M., Seeman, P., Houle, S., Kapur, S., & Wilson, A. A. (2006). Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography. Journal of Neurochemistry, 97(4), 1089-103.
Ginovart N, et al. Binding Characteristics and Sensitivity to Endogenous Dopamine of [11C]-(+)-PHNO, a New Agonist Radiotracer for Imaging the High-affinity State of D2 Receptors in Vivo Using Positron Emission Tomography. J Neurochem. 2006;97(4):1089-103. PubMed PMID: 16606355.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Binding characteristics and sensitivity to endogenous dopamine of [11C]-(+)-PHNO, a new agonist radiotracer for imaging the high-affinity state of D2 receptors in vivo using positron emission tomography. AU - Ginovart,Nathalie, AU - Galineau,Laurent, AU - Willeit,Matthaeus, AU - Mizrahi,Romina, AU - Bloomfield,Peter M, AU - Seeman,Philip, AU - Houle,Sylvain, AU - Kapur,Shitij, AU - Wilson,Alan A, Y1 - 2006/04/05/ PY - 2006/4/12/pubmed PY - 2006/6/23/medline PY - 2006/4/12/entrez SP - 1089 EP - 103 JF - Journal of neurochemistry JO - J Neurochem VL - 97 IS - 4 N2 - [11C]-(+)-PHNO (4-propyl-9-hydroxynaphthoxazine) is a new agonist radioligand that provides a unique opportunity to measure the high-affinity states of the D2 receptors (D2-high) using positron emission tomography (PET). Here we report on the distribution, displaceablity, specificity and modeling of [11C]-(+)-PHNO and compare it with the well characterized antagonist D2 radioligand, [11C]raclopride, in cat. [11C]-(+)-PHNO displayed high uptake in striatum with a mean striatal binding potential (BP) of 3.95 +/- 0.85. Pre-treatment with specific D1 (SCH23390), D2 (raclopride, haloperidol) and D3 receptor (SB-277011) antagonists indicated that [11C]-(+)-PHNO binding in striatum is specific to D2 receptors. Within-subject comparisons showed that [11C]-(+)-PHNO BP in striatum was almost 2.5-fold higher than that measured with [11C]-(-)-NPA ([11C]-(-)-N-propyl-norapomorphine). Comparison of the dose-effect of amphetamine (0.1, 0.5 and 2 mg/kg; i.v.) showed that [11C]-(+)-PHNO was more sensitive to the dopamine releasing effect of amphetamine than [11C]raclopride. Amphetamine induced up to 83 +/- 4% inhibition of [11C]-(+)-PHNO BP and only up to 56 +/- 8% inhibition of [11C]raclopride BP. Scatchard analyses of [11C]-(+)-PHNO and [11C]raclopride bindings in two cats showed that the Bmax obtained with the agonist (29.6 and 32.9 pmol/mL) equalled that obtained with the antagonist (30.6 and 33.4 pmol/mL). The high penetration of [11C]-(+)-PHNO in brain, its high signal-to-noise ratio, its favorable in vivo kinetics and its high sensitivity to amphetamine shows that [11C]-(+)-PHNO has highly suitable characteristics for probing the D2-high with PET. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/16606355/Binding_characteristics_and_sensitivity_to_endogenous_dopamine_of_[11C]__+__PHNO_a_new_agonist_radiotracer_for_imaging_the_high_affinity_state_of_D2_receptors_in_vivo_using_positron_emission_tomography_ L2 - https://doi.org/10.1111/j.1471-4159.2006.03840.x DB - PRIME DP - Unbound Medicine ER -