title: Quantitative analysis of dopamine transporters in human brain using [11C]PE2I and positron emission tomography: evaluation of reference tissue models.
abstract: OBJECTIVE
  Dopamine transporter (DAT) is a reuptake carrier of dopamine at presynapse that regulates dopaminergic neural transmission. [(11)C]PE2I is a cocaine analog developed as a potent positron emission tomography (PET) ligand for DAT with high selectivity. The aim of this study was to evaluate the applicability of quantification methods using reference tissue models for [(11)C]PE2I.
  
  
  METHODS
  Dynamic PET scans were performed in 6 young healthy male volunteers after an intravenous bolus injection of [(11)C]PE2I. Metabolite-corrected arterial plasma-input functions were obtained. Compartment model analysis and plasma-input Logan analysis were performed to determine the kinetic parameters and distribution volume (V (T)). The distribution volume ratio (DVR) was calculated as the ratio of V (T) in the cerebral region to that in the cerebellum. DVRs were also determined by the original multilinear reference tissue model method (MRTMo) and the simplified reference tissue model method (SRTM), comparing the results with those obtained from graphical analysis using arterial input function. To estimate errors in DVR calculated using the reference tissue model, a simulation study that focused on cerebellar kinetics and scan duration was performed.
  
  
  RESULTS
  The highest [(11)C]PE2I binding was observed in the striatum, followed by the midbrain and thalamus. The 2-tissue model was preferable to the 1-tissue model for describing the [(11)C]PE2I kinetics in the cerebellum. Both the measured and 90-min simulated data showed that reference tissue models caused an underestimation of DVR in the striatum. The simulation showed that 90-min scan duration was insufficient when cerebellar kinetics was described as a 1-tissue model. Nevertheless, DVR values determined by MRTMo and SRTM were in good agreement with those by the graphical approach in other lower binding regions.
  
  
  CONCLUSIONS
  Due to the [(11)C]PE2I kinetics in the cerebellum and limited scan duration for (11)C, MRTMo and SRTM underestimated the striatal DVR. Despite this limitation, the present study demonstrated the applicability of reference tissue models. Since DAT in the midbrain and thalamus is of interest in the pathophysiology of neuropsychiatric disease, this noninvasive quantitative analysis will be useful for clinical investigations.
authors.affiliation: Molecular Imaging Center, National Institute of Radiological Sciences, 4-9-1 Anagawa, Inage-ku, Chiba, 263-8555, Japan.
authors.forename: Chie
authors.initials: C
authors.lastname: Seki
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ito
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ichimiya
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arakawa
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ikoma
authors.forename: Miho
authors.initials: M
authors.lastname: Shidahara
authors.forename: Jun
authors.initials: J
authors.lastname: Maeda
authors.forename: Akihiro
authors.initials: A
authors.lastname: Takano
authors.forename: Hidehiko
authors.initials: H
authors.lastname: Takahashi
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kimura
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Suzuki
authors.forename: Iwao
authors.initials: I
authors.lastname: Kanno
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Suhara
mesh_terms: D000328:Adult; D001158:Arteries / Q000502:physiology; D001921:Brain / Q000098:blood supply / Q000378:metabolism* / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D008954:Models, Biological; D009662:Nortropanes / Q000378:metabolism*; D049268:Positron-Emission Tomography; D012016:Reference Values; D015203:Reproducibility of Results; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission; D013997:Time Factors; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; C113010:N-(3-iodoprop-2-enyl)-2-beta-carbomethoxy-3-(4-methylphenyl)nortropane; D009662:Nortropanes; D004298:Dopamine