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

Patrik Fazio, Per Svenningsson, Anton Forsberg, Erik G. Jönsson, Nahid Amini, Ryuji Nakao, Sangram Nag, Christer Halldin, Lars Farde, Andrea Varrone

Research output: Contribution to journalArticle

Abstract

18F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4?-methylphenyl) nortropane (18F-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 18F-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 18F-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 (BPND) estimated with the simplified reference tissue model and the Logan graphical analysis, using the cerebellum as a reference region. Time stability of BPND was examined to define the shortest acquisition protocol for quantitative studies. The wavelet-aided parametric imaging method was used to obtain high-resolution BPND 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 18F-FE-PE2I did not differ significantly between PD patients and controls. Stable estimates of BPND (<8% of the 93-min value) were obtained with the simplified reference tissue model using approximately 66 min of data. BPND 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: 18F-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 18F-FE-PE2I as an imaging tool of the nigrostriatal pathway.

Original languageEnglish
Pages (from-to)714-720
Number of pages7
JournalJournal of Nuclear Medicine
Volume56
Issue number5
DOIs
Publication statusPublished - May 1 2015

Keywords

  • Dopamine transporter
  • Nigra
  • Parkinson disease
  • PET
  • Substantia

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Medicine(all)

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    Fazio, P., Svenningsson, P., Forsberg, A., Jönsson, E. G., Amini, N., Nakao, R., Nag, S., Halldin, C., Farde, L., & Varrone, A. (2015). 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. Journal of Nuclear Medicine, 56(5), 714-720. https://doi.org/10.2967/jnumed.114.152421