[18F]‐6‐Fluorodopa PET scanning in Parkinson's disease after selective COMT inhibition with nitecapone (OR‐462)

Author:

Laihinen A.,Rinne J. O.,Rinne U. K.,Haaparanta M.,Ruotsalainen U.,Bergman J.,Solin O.

Abstract

PET studies were performed to investigate the effects of a new catechol-O-methyltransferase (COMT) inhibitor, nitecapone (OR-462 [3-(3,4-dihydroxy-5-nitrobenzylidene)-2,4-pentadione]), on the accumulation of dopamine in the striatuni and whether it is able to improve [18F]6-fluorodopa imaging of the brain. Altogether, three patients with Parkinson's disease (PD) and three normal volunteers were examined, first without nitecapone and then with an oral dose of 100 mg of nitecapone 1 hour before the IV injection of 3 mCi of [18F]6-fluorodopa. High-pressure liquid chromatography analysis of arterial plasma samples showed a significant reduction in the metabolic conversion rate from [18F]6-fluorodopa to [18F]3-O-methylfluorodopa after the administration of nitecapone. PET studies showed that nitecapone significantly (p < 0.05) increased the [18F]6-fluorodopa accumulation in the striatum both in PD patients and normal controls; the magnitude of this increase was 20.0 ± 5.58 (mean ± SEM). The ratio of radioactivity in the striatum and arterial plasma was increased 39.0 ± 5.0% (mean ± SEM) after the administration of nitecapone. Consequently, the quality of PET images after OR-462 was better, which has implications for future [18F]6-fluorodopa studies. In addition, COMT inhibition may have clinical advantages by improving levodopa treatment in PD.

Publisher

Ovid Technologies (Wolters Kluwer Health)

Subject

Neurology (clinical)

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