Quantitative Analysis of ¹⁸F-(E)-N-(3-Iodoprop-2-Enyl)-2β-Carbofluoroethoxy-3β-(4′-Methyl-Phenyl) Nortropane Binding to the Dopamine Transporter in Parkinson Disease

Abstract

nortropane ( 18 F-FE-PE2I) is a recently developed radioligand for the in vivo quantification of the dopamine transporter (DAT) in the striatum and substantia nigra (SN). The aim of this study was to examine the suitability of 18 F-FE-PE2I as a tool for imaging the nigrostriatal pathway in Parkinson disease (PD) with PET. Methods: Ten PD patients (9 men and 1 woman; mean age ± SD, 60 ± 9 y; Hoehn and Yahr, 1-2; Unified Parkinson Disease Rating Scale motor, 18.9 ± 6.7) and 10 controls (9 men and 1 woman; mean age ± SD, 60 ± 7 y) were included. PET measurements with 18 F-FE-PE2I were conducted for 93 min using the High-Resolution Research Tomograph. Venous blood was drawn to compare protein binding, parent fraction, and radiometabolite composition in PD patients and controls. Regions of interest for the caudate, putamen, ventral striatum, SN, and cerebellum were drawn on coregistered MR images. The outcome measure was the binding potential (BP ND ) estimated with the simplified reference tissue model and the Logan graphical analysis, using the cerebellum as a reference region. Time stability of BP ND was examined to define the shortest acquisition protocol for quantitative studies. The wavelet-aided parametric imaging method was used to obtain high-resolution BP ND images to compare DAT availability in the striatum and SN in PD patients and control subjects. Group differences were assessed with the unpaired t test (P , 0.05). Results: Parent, radiometabolite fractions, plasma concentration, and cerebellar uptake of 18 F-FE-PE2I did not differ significantly between PD patients and controls. Stable estimates of BP ND (,8% of the 93-min value) were obtained with the simplified reference tissue model using approximately 66 min of data. BP ND values in PD patients were significantly lower than those in controls (P , 0.05) in the caudate (2.54 ± 0.79 vs. 3.68 ± 0.56), putamen (1.39 ± 1.04 vs. 4.41 ± 0.54), ventral striatum (2.26 ± 0.93 vs. 3.30 ± 0.46), and SN (0.46 ± 0.20 vs. 0.68 ± 0.15). Conclusion: 18 F-FE-PE2I is clearly a suitable radioligand for DAT quantification and imaging of the nigrostriatal pathway in PD. Similar metabolism in controls and PD patients, suitability of the cerebellum as a reference region, and accuracy of quantification using approximately 66 min of PET data are advantages for noninvasive and simplified imaging protocols for PD studies. Finally, DAT loss in PD can be measured in both the striatum and the SN, supporting the utility of 18 F-FE-PE2I as an imaging tool of the nigrostriatal pathway.

Optimal Acquisition Time Window and Simplified Quantification of Dopamine Transporter Availability Using 18F-FE-PE2I in Healthy Controls and Parkinson Disease Patients

“…18 F-FE-PE2I is a promising imaging tool for in vivo quantification of DAT availability by means of PET (17,19), but so far the radioligand has not been investigated in conditions resembling a clinical setting. The noninvasive quantification methods previously validated for 18 F-FE-PE2I (SRTM, LoganRef, and WAPI) rely on the acquisition of a PET dynamic scan, which is not always feasible in nuclear medicine departments.…”

“…PD patients satisfied the clinical diagnosis of PD according to the U.K. Parkinson Disease Society Brain Bank diagnostic criteria. All characteristics of control subjects and patients as well as the PET experimental procedure have been previously described (19). Relevant demographic and clinical data are shown in Table 1.…”

“…The cerebellum was used as a reference region. The ROIs were projected to the parametric images using the MR-to-PET transformation to estimate regional BP ND (19).…”

“…The first applied study using 18 F-FE-PE2I in PD patients demonstrated that the radioligand has a similar metabolism in PD patients and control subjects and that it enables accurate quantification of DAT availability both in the striatum, at the axonal terminal level, and in the substantia nigra (SN), where the cell bodies of the dopaminergic neurons are located (19).…”

Parkinson’s Disease: Biomarkers, Treatment, and Risk Factors

“…The presence of presynaptic DAT in dopaminergic neurons of striatum and SN can be assessed with 18 F and/or 11 C radiolabeled dopamine analogs. These DAT radioligands include 18 F-dopamine ( 18 F-dopa) (Ibrahim et al, 2016), 18 F-FE-PE2I (Fazio et al, 2015), 18 F-β-CFT (Rinne et al, 1999), 18 F-LBT999 (Arlicot et al, 2017), and 11 C-methylphenidate. The VMAT2 quantification is also possible by using either 11 C or 18 F radiolabeled dihydrotetrabenazine (DTBZ) (Tong et al, 2008; Lin et al, 2013).…”