[(11)C]d-threo-methylphenidate PET in patients with Parkinson's disease and essential tremor

Abstract

Twenty Parkinson's disease (PD) patients, 6 patients with essential tremor and 10 healthy controls were studied with the dopamine transporter ligand [(11)C]d-threo-methylphenidate ([(11)C]dMP) and positron emission tomography (PET) to assess dopamine terminal loss in relation to disease duration and motor disability. Dopamine transporter availability was expressed as [(11)C]dMP binding potential (BP(dMP)) in percentage of the mean of healthy controls. In PD patients (age at onset 57.7 +/- 8.9 yrs; disease duration 5.2 +/- 3.3 yrs; UPDRS motor score 24.2 +/- 9.8; Hoehn & Yahr 2.1 +/- 0.8; mean +/- SD) BP(dMP) was reduced to 30% (range: 11-55%) in the putamen and 52% (range: 14-96%) in the caudate nucleus. BP(dMP) in the putamen closely correlated with the UPDRS motor score (r = -0.79, p < 0.001), and disease duration (r = -0.76, p < 0.001) but not with age at onset. The correlation with the UPDRS score depended on akinesia and rigidity, while the tremor scores were related neither to putamen nor caudate BP(dMP). Interestingly, when plotted over disease duration, PD patients with severe asymmetry of symptoms showed significantly lower BP(dMP) in the contralateral putamen (exponential fit: 34% at onset) than the other PD patients (41% at onset), indicating a different symptomatic threshold of these subgroups and an even closer correlation with the hypothetical "true" disease duration. The exponential fit across all patients indicated a mean symptomatic threshold of 37% contra- and 62% ipsilateral, corresponding with an observed mean BP(dMP) of 51% (average contra- and ipsilateral) in those patients with disease duration less than one year. No differences in BP(dMP) were observed between patients with essential tremor and healthy controls. [(11)C]dMP appears to be a useful and sensitive marker of dopaminergic dysfunction in PD and can be used to assess and monitor disease severity.