Progression in Parkinson's disease: A positron emission tomography study with a dopamine transporter ligand [18F]CFT

Abstract

We studied the rate of progression of striatal dopamine transporter function in Parkinson's disease (PD). Eight patients with early PD without antiparkinsonian medication and 7 healthy volunteers were investigated with [18F]CFT positron emission tomography (PET). The PET scan was carried out twice at an approximate 2-year interval. The uptake of [18F]CFT was calculated as a region-cerebellum:cerebellum ratio at 180 to 210 minutes after injection. At the first PET scan, the [18F]CFT uptake in PD patients in the putamen was 1.45 +/- 0.45 (mean +/- SD) (42% of the control mean) and 2.43 +/- 0.59 in the caudate nucleus (76% of the control mean). The ratios declined by the time of the second PET scan, and the rate of annual decline of the baseline mean in PD patients was 13.1% in the putamen and 12.5% in the caudate nucleus. In controls, the corresponding figures were 2.1% for the putamen and 2.9% for the caudate nucleus. The decline in [18F]CFT uptake was significantly higher in PD patients than in controls. Thus, dopamine transporter ligands such as [18F]CFT seem to be sensitive markers for the rate of progression in PD.

18F-FP-CIT PET imaging and SPM analysis of dopamine transporters in Parkinson’s disease in various Hoehn & Yahr stages

“…1, Table 1). In 23 patients with early PD (H & Y Stage 1.43 ± 0.51; motor UPDRS rating 22.0 ± 7.0), 18 F-FP-CIT binding was significantly reduced (p < 0.01) to 70.9% (caudate), 46.8% (anterior putamen) and 24.0% (posterior putamen) of the normal mean. In 18 patients with advanced PD (H & Y Stage 3.61 ± 0.5; motor UPDRS rating 36.7 ± 7.4), striatal 18 F-FP-CIT binding was significantly decreased (p < 0.01) to 52.0%, 34.5% and 16.5% respectively of the corresponding subregions in the control group.…”

“…The images were then smoothed using an isotropic 10-mm kernel to account for variation in striatum and individual variability in structure-function relationships. 18 F-FP-CIT binding difference was examined for all voxels over the whole brain and appropriate linear contrasts were used to derive the between-group (unpaired) t statistic. The SPM{t}s were then transformed to the unit normal distribution (SPM{Z}) and converted to Z scores.…”

“…Among them, two major approaches were used. 18 F-dopa uptake in the striatum reflects the density of striatal dopaminergic terminals and the conversion of 18 F-dopa to and storage as 18 F-dopamine. However, it has been suggested that 18 F-dopa assessment might overestimate the number of striatal dopaminergic nerve terminals in early stage of PD, because the loss of dopaminergic synapses is partially compensated for by increased dopamine turnover in the surviving terminals [2,[7][8][9][10].…”

“…FPCIT is a highaffinity cocaine analog binding specifically to DAT. When it is labeled by 18 F, it has fast kinetics and high signal-to-noise ratios and is suitable for PET neuroimaging [5,15,16]. Previous work indicated that DAT imaging might be more sensitive in detecting early stage of PD than 18 F-dopa imaging [7,17].…”

“…Previous work indicated that DAT imaging might be more sensitive in detecting early stage of PD than 18 F-dopa imaging [7,17]. There has been, however, some controversy over whether DAT imaging might be used as a biomarker for assessing the severity and progression of PD, and for evaluating the efficacy of neuroprotective treatments [3,[18][19][20]. In longitudinal studies, DAT ligands with both PET and SPECT have demonstrated no significant correlation between the reduction in striatal DAT and the change in clinical severity in PD [19].…”