desmethoxyfallypride and Parkinson-Disease

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.

Topics: Adult; Aged; Brain; Diagnosis, Differential; Female; Humans; Male; Middle Aged; Parkinson Disease; Positron-Emission Tomography; Radiopharmaceuticals; Receptors, Dopamine D2; Reproducibility of Results; Salicylamides; Sensitivity and Specificity

[(18)F]desmethoxyfallypride ([(18)F]DMFP) is a promising tracer for longitudinal assessment of striatal dopamine D2/D3-receptor (D2R) availability by positron emission tomography (PET) in small animal models. We explored the feasibility of [(18)F]DMFP-PET to image D2R availability in rat models of Huntington's (HD) and Parkinson's disease (PD).. Animals received either unilateral intrastriatal quinolinic acid lesions or medial forebrain bundle injections of 6-OHDA to produce the loss of striatal projection neurones or deplete the striatal dopamine, corresponding to established animal models for HD and PD, respectively. Three weeks after lesioning, PET scans were acquired on a microPET Focus 120 system following the tail vein injection of [(18)F]DMFP.. [(18)F]DMFP-PET clearly visualized lesion induced decreases and increases of D2R availability. In vivo estimates of D2R binding and changes thereof gained by pharmacokinetic analyses correlated significantly with D2R density and its change provided by in vitro [(3)H]raclopride-autoradiography.. In conclusion, [(18)F]DMFP-PET is a suitable method for in vivo D2R-assessment in preclinical research, e.g for monitoring cell-based therapies.

Topics: Animals; Disease Models, Animal; Huntington Disease; Parkinson Disease; Positron-Emission Tomography; Raclopride; Radioactive Tracers; Rats; Receptors, Dopamine D2; Receptors, Dopamine D3; Salicylamides

We evaluated the utility of the selective dopamine D(2/3) receptor ligand (18)F-desmethoxyfallypride ((18)F-DMFP) for the differential diagnosis of patients with idiopathic parkinsonian syndrome (IPS) and nonidiopathic parkinsonian syndrome (non-IPS). On the basis of the superior sensitivity of PET, we hypothesized that (18)F-DMFP should have properties for the differential diagnosis of these syndromes superior to what has been reported for the more conventional SPECT procedures.. A series of 81 patients with parkinsonism (26 women, 55 men; mean age +/- SD, 68 +/- 11 y) were included in this retrospective analysis. A 30-min (18)F-DMFP PET recording was acquired starting 1 h after injection of the tracer (180-200 MBq, intravenously). The specific binding (SB) in divisions of the striatum was calculated relative to the occipital cortex using an observer-independent semiautomatic volume-of-interest-based technique. The optimal SB threshold was defined by means of receiver-operating-characteristic analysis, which was also used for the evaluation of the diagnostic performance of SB, ratios between striatal subregions, and absolute asymmetries in SB.. Significant differences (P < 0.001) were found in striatal SB between IPS and non-IPS, most notably in the posterior putamen, for which the diagnostic power for discrimination of IPS and non-IPS was the highest (sensitivity, 87%; specificity, 96%; and accuracy, 91%). A further gain of diagnostic power (sensitivity, 92%; specificity, 96%; and accuracy, 94%) was obtained through discriminant analysis combining 3 parameters: SB of the posterior putamen, the posterior-to-anterior putamen ratio, and the posterior putamen-to-caudate ratio.. (18)F-DMFP PET is useful for the differential diagnosis of IPS and non-IPS in patients with parkinsonism. The findings are consistent with relative sparing of D(2/3) receptors in the dopamine-denervated putamen of IPS patients, in contrast to a more substantial loss of striatal dopamine receptors in non-IPS patients. The PET procedure for this differential diagnosis was superior to the reported experience with (123)I-iodobenzamide SPECT.

Topics: Adult; Aged; Aged, 80 and over; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Ligands; Male; Middle Aged; Neostriatum; Parkinson Disease; Positron-Emission Tomography; Receptors, Dopamine D2; Receptors, Dopamine D3; Retrospective Studies; ROC Curve; Salicylamides; Sensitivity and Specificity