Brain region binding of the D2/3 agonist [11C]-(+)-PHNO and the D2/3 antagonist [11C]raclopride in healthy humans
| Autor: | Philip Seeman, Irina Vitcu, Pablo Rusjan, Romina Mizrahi, David C. Mamo, Shitij Kapur, Ariel Graff-Guerrero, Nathalie Ginovart, Alan A. Wilson, Matthaeus Willeit |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Time Factors Dopamine Striatum ddc:616.89 Substantia Nigra/diagnostic imaging/metabolism Basal ganglia Radioligand Tissue Distribution Carbon Radioisotopes Receptors Dopamine D2/agonists/metabolism Research Articles Raclopride Brain Mapping Dopamine Agonists/metabolism/pharmacokinetics Radiological and Ultrasound Technology Chemistry Putamen Substantia Nigra Dopamine D2 Receptor Antagonists Globus pallidus Neurology Dopamine Agonists Female Anatomy medicine.drug Adult Agonist medicine.medical_specialty Raclopride/metabolism/pharmacokinetics medicine.drug_class Globus Pallidus Binding Competitive Binding Competitive/drug effects/physiology Internal medicine Brain Mapping/methods Oxazines medicine Humans Radiology Nuclear Medicine and imaging Corpus Striatum/diagnostic imaging/metabolism Globus Pallidus/diagnostic imaging/metabolism Neostriatum/diagnostic imaging/metabolism Receptors Dopamine D2 Antagonist Positron-Emission Tomography/methods Dopamine Antagonists/metabolism/pharmacokinetics Corpus Striatum Dopamine/metabolism Neostriatum Endocrinology nervous system Positron-Emission Tomography Dopamine Antagonists Oxazines/metabolism/pharmacokinetics Neurology (clinical) Neuroscience |
| Zdroj: | Hum Brain Mapp Human Brain Mapping, Vol. 29, No 4 (2008) pp. 400-10 |
| ISSN: | 1097-0193 1065-9471 |
| DOI: | 10.1002/hbm.20392 |
| Popis: | 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. Hum Brain Mapp 2008. © 2007 Wiley‐Liss, Inc. |
| Databáze: | OpenAIRE |
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