The dopamine D2 receptor ligand 18F-desmethoxyfallypride: an appropriate fluorinated PET tracer for the differential diagnosis of parkinsonism

Abstract

For therapeutic and prognostic reasons it is important to differentiate between idiopathic parkinsonian syndrome (IPS, Parkinson's disease) and atypical parkinsonian syndromes (APS) like multiple system atrophy or progressive supranuclear palsy. Whereas IPS patients usually show a normal or upregulated postsynaptic dopamine D2 receptor profile, APS patients present decreased postsynaptic tracer binding. The aim of this prospective study was to evaluate the D2 receptor antagonist fluorine-18 desmethoxyfallypride (18F-DMFP), a recently developed positron emission tomography (PET) tracer with better clinical availability than carbon-11 raclopride, for the differential diagnosis of IPS versus APS. The study included 16 healthy control subjects and 35 patients with clinically diagnosed parkinsonism (16 IPS patients, 19 APS patients). All patients underwent PET imaging after injection of 180-200 MBq 18F-DMFP. Receiver operating characteristic (ROC) analyses were performed in order to assess the diagnostic performance of 18F-DMFP PET. We found the striatal 18F-DMFP uptake ratio to be significantly (P<0.01) reduced in the APS patients (2.44+/-0.42) compared with the healthy control subjects (3.61+/-0.43) and the IPS patients (3.21+/-0.78), whereas the uptake ratios of the IPS patients and the control subjects did not differ significantly. For the differential diagnosis of APS versus IPS, the ROC analysis of caudate 18F-DMFP binding showed a specificity, sensitivity and accuracy of 100%, 74% and 86%, respectively, as well as positive and negative predictive values of 100% and 76%, respectively. Based on these first clinical results, we consider 18F-DMFP to be an appropriate PET tracer for the differential diagnosis of parkinsonian syndromes, with the advantage of better clinical availability than 11C-labelled D2 radioligands.