title: 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: (18)F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'-methyl-phenyl) 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).
  
  
  CONCLUSIONS
  (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.
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden patrik.fazio@ki.se.
authors: Patrik
authors: P
authors: Fazio
authors: Karolinska Institutet, Department of Neurology and Clinical Neuroscience, Centre for Molecular Medicine, Stockholm, Sweden.
authors: Per
authors: P
authors: Svenningsson
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors: Anton
authors: A
authors: Forsberg
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden Norment, Institute of Clinical Medicine, University of Oslo, Oslo, Norway; and.
authors: Erik G
authors: EG
authors: Jönsson
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors: Nahid
authors: N
authors: Amini
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors: Ryuji
authors: R
authors: Nakao
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors: Sangram
authors: S
authors: Nag
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors: Christer
authors: C
authors: Halldin
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden AstraZeneca Translational Science Centre at Karolinska Institutet, Stockholm, Sweden.
authors: Lars
authors: L
authors: Farde
authors: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors: Andrea
authors: A
authors: Varrone
mesh_terms: D000368:Aged; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009662:Nortropanes / Q000378:metabolism*; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011485:Protein Binding; D013378:Substantia Nigra / Q000000981:diagnostic imaging / Q000378:metabolism
chemical_list: C543996:(E)-N-(3-iodoprop-2-enyl)-2beta-carbofluoroethoxy-3beta-(4'-methyl-phenyl) nortropane; D050483:Dopamine Plasma Membrane Transport Proteins; D009662:Nortropanes
keywords: PET; Parkinson disease; dopamine transporter; substantia nigra