Striatal [18F]fluorodopa utilization after COMT inhibition with entacapone studied with PET in advanced Parkinson's disease.

H M Ruottinen, J O Rinne, U H Ruotsalainen, J R Bergman, V J Oikonen, M T Haaparanta, O H Solin, A O Laihinen, U K Rinne
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引用次数: 37

Abstract

The effect of peripheral catechol-O-methyltransferase (COMT) inhibition with entacapone on striatal uptake of 6-[18F]fluoro-L-dopa (FDOPA) was studied with PET both without and with entacapone in fifteen advanced parkinsonian patients and six healthy controls. Entacapone significantly enhanced the fraction of unmetabolized FDOPA in plasma from 16% to about 50% at 80 minutes after FDOPA injection in all subjects. The striatal to occipital ratios and the striatal FDOPA uptake, expressed as a modified decarboxylation coefficient (k3R0), was significantly increased in healthy controls, whereas in parkinsonian patients the increase was significant only in the caudate. On the other hand, the influx constant (Ki) decreased significantly in the caudate and putamen in parkinsonian patients; in healthy controls the Ki remained virtually unchanged. Effective peripheral COMT inhibition markedly increased the fraction of FDOPA in plasma and thus its availability in the brain for decarboxylation both in patients and control subjects. However, the change in striatal FDOPA uptake was modest in the advanced parkinsonian patients as compared to that in control subjects, because of the advanced disease, decreased storage capacity, or both.

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应用PET研究晚期帕金森病患者恩他卡酮抑制COMT后纹状体[18F]氟多巴的利用。
应用PET研究了恩他卡酮对外周儿茶酚- o-甲基转移酶(COMT)的抑制作用对15例晚期帕金森患者和6例健康对照6-[18F]氟左旋多巴(FDOPA)纹状体摄取的影响。注射FDOPA后80分钟,恩他卡朋显著提高血浆中未代谢FDOPA的比例,从16%提高到约50%。纹状体与枕状体的比率和纹状体FDOPA摄取(以修饰脱羧系数(k3R0)表示)在健康对照中显著增加,而在帕金森病患者中,这种增加仅在尾状体中显著。另一方面,帕金森病患者尾状核和壳核的内流常数(Ki)显著降低;在健康对照组中,Ki几乎保持不变。有效的外周COMT抑制显著增加了血浆中FDOPA的含量,从而在患者和对照组中增加了FDOPA在大脑中脱羧的可用性。然而,与对照组相比,晚期帕金森病患者纹状体FDOPA摄取的变化不大,这是由于疾病晚期,储存能力下降,或两者兼而有之。
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