To assess the necessity of withdrawing dopaminergic medication in Parkinson's disease (PD) patients for accurate estimation of adenosine 2A receptor (A 2A R) availability using [ 11 C]TMSX PET imaging. This was accomplished by studying the short-term effect of the cessation of dopaminergic medication on A 2A R availability in non-dyskinetic patients with PD treated with dopaminergic medication. Methods: Eight PD patients (age 67.9 ± 5.6 years; 6 men, 2 women) without dyskinesia were enrolled in this study. A 2A R availability was measured using PET imaging with a [7-methyl-11 C]-(E)-8-(3,4,5-trimethoxystyryl)-1,3,7-trimethylxanthine ([ 11 C]TMSX) radioligand after a short term cessation of dopaminergic medication (12hrs for levodopa, 24hrs for dopamine agonists and MAO-B inhibitors). Repeated PET imaging was performed while the patients were back 'on' their regular dopaminergic medication (median 13 days after first imaging). Conventional MRI was acquired for anatomical reference. Specific binding of [ 11 C]TMSX was quantified as distribution volume ratios (DVR) for caudate, pallidum and putamen using Logan graphical method with clustered gray matter reference region. Results: No significant differences were observed for the DVRs in all three striatal regions between 'on' and 'off' medication states. Strong correlations were also observed between the two states. Statistical equivalence was found in pallidum (TOST equivalence test, p = 0.045) and putamen (TOST equivalence test, p = 0.022), but not in caudate DVR (TOST equivalence test, p = 0.201) between the two medication states. Conclusions: Our results show that dopaminergic medication has no significant short-term effect on the availability of A 2A receptors in putamen and pallidum of patients with PD. However, relatively poor repeatability was demonstrated in the caudate.
Introduction Adenosine 2A (A2A) receptors co-localize with dopamine D2 receptors in striatopallidal medium spiny neurons of the indirect pathway. A2A receptor activation in the striatum or pallidum decreases D2 signaling. In contrast, A2A receptor antagonism may help potentiate it. Furthermore, previous PET studies have shown increased A2A receptor availability in striatum of late-stage PD patients with dyskinesia. However, human in vivo evidence for striatal A2A receptor availability in early-stage PD is limited. This study aimed to investigate possible differences in A2A receptor availability in the striatum and pallidum of early- and moderate-stage PD patients without dyskinesias. Methods Brain MRI and PET with [11C]TMSX radioligand, targeting A2A receptors, was performed in 9 patients with early- and 9 with moderate-stage PD without dyskinesia and in 6 healthy controls. Distribution volume ratios (DVR) were calculated to assess specific [11C]TMSX binding in caudate, putamen and pallidum. Results A2A receptor availability (DVR) was decreased in the bilateral caudate of early-stage PD patients when compared with healthy controls (P = 0.02). Conversely, DVR was increased bilaterally in the pallidum of moderate-stage PD patients compared to healthy controls (P = 0.03). Increased mean striatal DVR correlated with higher motor symptom severity ($$rho$$ rho = 0.47, P = 0.02). Conclusion Our results imply regional and disease stage-dependent changes in A2A receptor signaling in PD pathophysiology and in response to dopaminergic medication.
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