title: Use of 11C-PE2I PET in differential diagnosis of parkinsonian disorders.
abstract: In idiopathic Parkinson disease and atypical parkinsonian disorders, central dopaminergic and overall brain functional activity are altered to different degrees, causing difficulties in achieving an unambiguous clinical diagnosis. A dual examination using (123)I-FP-CIT ((123)I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane, or (123)I-ioflupane) SPECT and(18)F-FDG PET provides complementary information on dopamine transporter (DAT) availability and overall brain functional activity, respectively. Parametric images based on a single, dynamic (11)C-PE2I (N-(3-iodoprop-2E-enyl)-2β-carbomethoxy-3β-(4-methyl-phenyl)nortropane) scan potentially supply both DAT availability (nondisplaceable binding potential [BPND]) and relative cerebral blood flow (relative delivery [R1]) at voxel level. This study aimed to evaluate the validity of (11)C-PE2I PET against the dual-modality approach using (123)I-FP-CIT SPECT and (18)F-FDG PET.
  
  
  METHODS
  Sixteen patients with parkinsonian disorders had a dual examination with (18)F-FDG PET and (123)I-FP-CIT SPECT following clinical routines and additionally an experimental (11)C-PE2I PET scan. Parametric BPND and R1 images were generated using receptor parametric mapping with the cerebellum as a reference. T1-weighted MR imaging was used for automated definition of volumes of interest (VOI). The DAT VOIs included the basal ganglia, whereas the overall brain functional activity was examined using VOIs across the brain. BPND and R1 values were compared with normalized (123)I-FP-CIT and (18)F-FDG uptake values, respectively, using Pearson correlations and regression analyses. In addition, 2 masked interpreters evaluated the images visually, in both the routine and the experimental datasets, for comparison of patient diagnoses.
  
  
  RESULTS
  Parametric (11)C-PE2I BPND and R1 images showed high consistency with (123)I-FP-CIT SPECT and (18)F-FDG PET images. Correlations between (11)C-PE2I BPND and (123)I-FP-CIT uptake ratios were 0.97 and 0.76 in the putamen and caudate nucleus, respectively. Regional (11)C-PE2I R1 values were moderately to highly correlated with normalized (18)F-FDG values (range, 0.61-0.94). Visual assessment of DAT availability showed a high consistency between (11)C-PE2I BPND and (123)I-FP-CIT images, whereas the consistency was somewhat lower for appraisal of overall brain functional activity using (123)I-FP-CIT and (18)F-FDG images. Substantial differences were found between clinical diagnosis and both neuroimaging diagnoses.
  
  
  CONCLUSIONS
  A single, dynamic (11)C-PE2I PET investigation is a powerful alternative to a dual examination with (123)I-FP-CIT SPECT and (18)F-FDG PET for differential diagnosis of parkinsonian disorders. A large-scale patient study is, however, needed to further investigate distinct pathologic patterns in overall brain functional activity for various parkinsonian disorders.
authors.affiliation: PET Centre, Department of Medical Imaging, Uppsala University Hospital, Uppsala, Sweden Section of Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden lieuwe.appel@akademiska.se.
authors.forename: Lieuwe
authors.initials: L
authors.lastname: Appel
authors.affiliation: Section of Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: My
authors.initials: M
authors.lastname: Jonasson
authors.affiliation: PET Centre, Department of Medical Imaging, Uppsala University Hospital, Uppsala, Sweden Section of Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Torsten
authors.initials: T
authors.lastname: Danfors
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Dag
authors.initials: D
authors.lastname: Nyholm
authors.affiliation: Department of Neuroscience, Neurology, Uppsala University, Uppsala, Sweden; and.
authors.forename: Håkan
authors.initials: H
authors.lastname: Askmark
authors.affiliation: Section of Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden Medical Physics, Uppsala University Hospital, Uppsala, Sweden.
authors.forename: Mark
authors.initials: M
authors.lastname: Lubberink
authors.affiliation: PET Centre, Department of Medical Imaging, Uppsala University Hospital, Uppsala, Sweden Section of Nuclear Medicine and PET, Department of Radiology, Oncology, and Radiation Sciences, Uppsala University, Uppsala, Sweden.
authors.forename: Jens
authors.initials: J
authors.lastname: Sörensen
mesh_terms: D000368:Aged; D001331:Automation; D002250:Carbon Radioisotopes; D003937:Diagnosis, Differential; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009662:Nortropanes; D020734:Parkinsonian Disorders / Q000175:diagnosis / Q000000981:diagnostic imaging*; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D015203:Reproducibility of Results; D015899:Tomography, Emission-Computed, Single-Photon
chemical_list: D002250:Carbon Radioisotopes; D050483:Dopamine Plasma Membrane Transport Proteins; C402415:I123-PE2I; D007457:Iodine Radioisotopes; D009662:Nortropanes; D019275:Radiopharmaceuticals; C519528:ioflupane
keywords: DAT; PET; SPECT; dopamine transporter; overall brain functional activity; parkinsonism