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Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

Mishina M, Ishiwata K, Naganawa M, Kimura Y, Kitamura S, Suzuki M, Hashimoto M, Ishibashi K, Oda K, Sakata M, Hamamoto M, Kobayashi S, Katayama Y, Ishii K - PLoS ONE (2011)

Bottom Line: We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test).In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test).In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus.

View Article: PubMed Central - PubMed

Affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan. mishina@nms.ac.jp

ABSTRACT
Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

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Related in: MedlinePlus

Scattergrams for binding parameters of [11C]TMSX, [11C]CFT and [11C]RAC in the striata of drug-naïve patients.The binding parameter for [11C]TMSX was expressed as DVR, and parameters for [11C]CFT and [11C]RAC were expressed as URI. There was no significant correlation among these variables.
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pone-0017338-g003: Scattergrams for binding parameters of [11C]TMSX, [11C]CFT and [11C]RAC in the striata of drug-naïve patients.The binding parameter for [11C]TMSX was expressed as DVR, and parameters for [11C]CFT and [11C]RAC were expressed as URI. There was no significant correlation among these variables.

Mentions: Figure 3 demonstrates the lack of significant correlation among the DVR for [11C]TMSX, the URI for [11C]CFT and the URI for [11C]RAC in the bilateral striata of drug-naïve patients. Specifically, there was no significant correlation among the following variables; the DVR for [11C]TMSX versus the URI for [11C]CFT (Figure 3A and 3D), the DVR for [11C]TMSX versus the URI for [11C]RAC (Figure 3B and 3E), and the URI for [11C]CFT versus the URI for [11C]RAC (Figure 3C and 3F).


Adenosine A(2A) receptors measured with [C]TMSX PET in the striata of Parkinson's disease patients.

Mishina M, Ishiwata K, Naganawa M, Kimura Y, Kitamura S, Suzuki M, Hashimoto M, Ishibashi K, Oda K, Sakata M, Hamamoto M, Kobayashi S, Katayama Y, Ishii K - PLoS ONE (2011)

Scattergrams for binding parameters of [11C]TMSX, [11C]CFT and [11C]RAC in the striata of drug-naïve patients.The binding parameter for [11C]TMSX was expressed as DVR, and parameters for [11C]CFT and [11C]RAC were expressed as URI. There was no significant correlation among these variables.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3046146&req=5

pone-0017338-g003: Scattergrams for binding parameters of [11C]TMSX, [11C]CFT and [11C]RAC in the striata of drug-naïve patients.The binding parameter for [11C]TMSX was expressed as DVR, and parameters for [11C]CFT and [11C]RAC were expressed as URI. There was no significant correlation among these variables.
Mentions: Figure 3 demonstrates the lack of significant correlation among the DVR for [11C]TMSX, the URI for [11C]CFT and the URI for [11C]RAC in the bilateral striata of drug-naïve patients. Specifically, there was no significant correlation among the following variables; the DVR for [11C]TMSX versus the URI for [11C]CFT (Figure 3A and 3D), the DVR for [11C]TMSX versus the URI for [11C]RAC (Figure 3B and 3E), and the URI for [11C]CFT versus the URI for [11C]RAC (Figure 3C and 3F).

Bottom Line: We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test).In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test).In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus.

View Article: PubMed Central - PubMed

Affiliation: Positron Medical Center, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan. mishina@nms.ac.jp

ABSTRACT
Adenosine A(2A) receptors (A2ARs) are thought to interact negatively with the dopamine D(2) receptor (D2R), so selective A2AR antagonists have attracted attention as novel treatments for Parkinson's disease (PD). However, no information about the receptor in living patients with PD is available. The purpose of this study was to investigate the relationship between A2ARs and the dopaminergic system in the striata of drug-naïve PD patients and PD patients with dyskinesia, and alteration of these receptors after antiparkinsonian therapy. We measured binding ability of striatal A2ARs using positron emission tomography (PET) with [7-methyl-(11)C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([(11)C]TMSX) in nine drug-naïve patients with PD, seven PD patients with mild dyskinesia and six elderly control subjects using PET. The patients and eight normal control subjects were also examined for binding ability of dopamine transporters and D2Rs. Seven of the drug-naïve patients underwent a second series of PET scans following therapy. We found that the distribution volume ratio of A2ARs in the putamen were larger in the dyskinesic patients than in the control subjects (p<0.05, Tukey-Kramer post hoc test). In the drug-naïve patients, the binding ability of the A2ARs in the putamen, but not in the head of caudate nucleus, was significantly lower on the more affected side than on the less affected side (p<0.05, paired t-test). In addition, the A2ARs were significantly increased after antiparkinsonian therapy in the bilateral putamen of the drug-naïve patients (p<0.05, paired t-test) but not in the bilateral head of caudate nucleus. Our study demonstrated that the A2ARs in the putamen were increased in the PD patients with dyskinesia, and also suggest that the A2ARs in the putamen compensate for the asymmetrical decrease of dopamine in drug-naïve PD patients and that antiparkinsonian therapy increases the A2ARs in the putamen. The A2ARs may play an important role in regulation of parkinsonism in PD.

Show MeSH
Related in: MedlinePlus