title: Optimal Acquisition Time Window and Simplified Quantification of Dopamine Transporter Availability Using 18F-FE-PE2I in Healthy Controls and Parkinson Disease Patients.
abstract: 18F-(E)-N-(3-iodoprop-2-enyl)-2β-carbofluoroethoxy-3β-(4'methylphenyl)nortropane (18F-FE-PE2I) is a newly developed dopamine transporter (DAT) PET radioligand. Full quantification methods rely on dynamic acquisition of18F-FE-PE2I, but in a clinical setting a simplified protocol is preferable. The aims of this study were to identify the optimal acquisition time window for18F-FE-PE2I and to validate the specific binding ratio (SBR) as a simplified quantification method.
  
  
  METHODS
  Ten Parkinson disease (PD) patients and 10 controls were included. Ninety-three-min dynamic PET measurements with18F-FE-PE2I were conducted using the high-resolution research tomograph (HRRT). The dynamic measurement was also smoothed to the resolution of a clinical PET system (HR). Regions of interest for the caudate, putamen, ventral striatum, substantia nigra (SN), and cerebellum were manually drawn on coregistered MR images. The outcome measure was the SBR, and the gold standard was the binding potential obtained with wavelet-aided parametric imaging (WAPI BPND). The cerebellum was used as a reference region. In a preliminary analysis, SBR was computed for 8 time windows (SBRdyn). Linear regression analysis and Bland-Altman plots were used to select the optimal acquisition time window. An average image from the selected time window was created, from which new SBR values (SBR calculated on the average image on the HRRT and SBR calculated on the average image on the simulated HR images) were calculated and compared with WAPI BPNDThe effect size was calculated.
  
  
  RESULTS
  SBRdynvalues for the time window between 16.5 and 42 min correlated best with WAPI BPND(r2= 0.98, P < 0.001). Significant correlations (P < 0.001) were observed between SBRHRand WAPI-BPND(r2= 0.95 in controls and 0.97 in PD patients). In the striatum, SBRHRvalues were 37% lower than BPNDin controls, 29% in PD patients, whereas in the SN the underestimation was 22% in controls and 15% in PD patients. Similar effect sizes for BPNDand SBRHRwere found in the caudate (0.6), putamen (1.7 and 1.4), ventral striatum (0.7), and SN (0.5 and 0.4).
  
  
  CONCLUSIONS
  A single18F-FE-PE2I acquisition between 16.5 and 42 min provides the best outcome measure for simplified DAT quantification. Despite underestimation of the BPND, the SBR can be used in a clinical setting as a valid quantification method for DAT using18F-FE-PE2I, because it provides differentiation similar to BPNDbetween controls and PD patients.
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden Sapienza University of Rome, Department of Medical-Surgical Sciences and of Translational Medicine, Nuclear Medicine Unit, Rome, Italy idasonni@gmail.com.
authors.forename: Ida
authors.initials: I
authors.lastname: Sonni
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors.forename: Patrik
authors.initials: P
authors.lastname: Fazio
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors.forename: Martin
authors.initials: M
authors.lastname: Schain
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors.forename: Christer
authors.initials: C
authors.lastname: Halldin
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Molecular Medicine, Stockholm, Sweden; and.
authors.forename: Per
authors.initials: P
authors.lastname: Svenningsson
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden AstraZeneca Translational Science Centre at Karolinska Institutet, PET CoE, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Farde
authors.affiliation: Karolinska Institutet, Department of Clinical Neuroscience, Centre for Psychiatry Research, Stockholm, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Varrone
mesh_terms: D016022:Case-Control Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009662:Nortropanes; D010300:Parkinson Disease / Q000000981:diagnostic imaging* / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000379:methods*; D013997:Time Factors
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: FE-PE2I; PET; Parkinson disease; dopamine transporter; quantification