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@INPROCEEDINGS{Sabri:132106,
      author       = {Sabri, O (Corresponding author) and Wilke, S and Graef, S
                      and Becker, G and Hesse, S and Sattler, B and Schoenknecht,
                      P and Wagenknecht, Gudrun and Smits, R and Hoepping, A and
                      Steinbach, J and Brust, P},
      title        = {{PET} {I}maging of {C}erebral {N}icotinic {A}cetylcholine
                      {R}eceptors (n{AC}h{R}s) in {E}arly {A}lzheimer’s
                      {D}isease ({AD}) {A}ssessed with the {N}ew {R}adioligand
                      (–)-[18{F}]{N}orchloro-{F}luoro-{H}omoepibatidine
                      ((–)-[18{F}]{F}lubatine)},
      reportid     = {FZJ-2013-01345},
      year         = {2012},
      abstract     = {Objectives: Post mortem studies have shown a degeneration
                      of cholinergic neurons in the brain of AD-patients. Further
                      evidence suggests that the loss of nAChRs is a major
                      contributor to the cognitive deterioration in AD, whereby
                      the alpha4beta2-nAChR subtype is thought to be the most
                      severely reduced in the onset of AD. Using 2-[18F]F-A85380
                      PET we showed a significant decline in alpha4beta2-nAChRs in
                      early AD-patients which correlated significantly with the
                      loss of cognitive function (Sabri et al. 2008; Kendziorra et
                      al. 2010). However, this tracer was not well suited as a
                      biomarker in a routine clinical set-up for early
                      AD-diagnosis because of unfavourable properties (slow
                      kinetics, long acquisition times up to 7 hours, limited
                      alpha4beta2-receptor-selectivity). We, therefore developed
                      the new radiotracer (-)-[18F]NCFHEB (denominated as
                      [18F]Flubatine) which is an epibatidine derivative with low
                      toxicity in humans), with significantly improved brain
                      uptake, nAChR affinity and selectivity (Brust et al. 2008).
                      Here, we present the results of the worldwide first ongoing
                      [18F]Flubatine-PET study in humans. Methods: 16 mild
                      AD-patients (NINCDS-ADRDA, age 74.4±6.6, MMSE 23.7±2.8)
                      and 11 age-matched healthy controls (HC, age 69.6±5.1, MMSE
                      28.5±0.9) underwent [18F]Flubatine-PET (370 MBq,
                      3D-acquisition, ECAT Exact HR+). All were nonsmokers and
                      naïve for central acting medication. In each subject, 4
                      scans (41 frames) were acquired from 0-270 min post
                      injection and motion correction was performed with SPM2.
                      Kinetic modeling was applied to the VOI-based
                      tissue-activity curves generated for 29 brain regions
                      (irregularly anatomically defined via MRI-coregistration)
                      using a one tissue compartment model with measured arterial
                      input-function. Total distribution volume (DV) and binding
                      potential (BP, reference region: corpus callosum) were used
                      to characterize specific binding. Additionally, parametric
                      images of DV were computed (Logan plot). Results: Image
                      quality of [18F]Flubatine scans was clearly superior to
                      2-[18F]F-A85380, and a 20 minutes scan already adequate for
                      visual analysis. All 29 regions were well described with one
                      tissue compartment. PET data acquired over only 90 minutes
                      were sufficient to estimate all kinetic parameters of all
                      VOIs (30 minutes sufficient for modelling of all cortical
                      VOIs respectively) precisely indicating a fast binding
                      kinetic (much faster than for 2-[18F]F-A85380). DVs in HCs
                      increase as expected with receptor density: Corpus callosum
                      (DV: 5.32±0,66), temporal (8.92±0.45), posterior cingulate
                      (9.03±0.55), pons (10.97±0.95), thalamus (24.92±3.56).
                      The AD-patients showed significant BP reductions in distinct
                      cortical regions (p<0.05) compared to HCs. Conclusions: Due
                      to significant shorter acquisition time, higher brain
                      uptake, faster kinetics and superior image quality
                      [18F]Flubatine appears to be a much more valuable tracer
                      than 2-[18F]F-A85380 to image alpha4beta2-nAChRs in humans.
                      Furthermore, full kinetic modelling (1-tissue compartment
                      model) is accurately possible within 90 minutes in all VOIs,
                      and within 30 minutes in all cortical VOIs. In keeping with
                      its diagnostic properties, early AD-patients show declines
                      of alpha4beta2-nAChRs in distinct cortical regions typically
                      affected by AD-pathology. These results indicate that
                      Flubatine-PET could have a great potential to be tested as a
                      biomarker for early AD-diagnosis.},
      month         = {Aug},
      date          = {2012-08-09},
      organization  = {The 9th International Symposium on
                       Functional Neuroreceptor Mapping of the
                       Living Brain, Baltimore (USA), 9 Aug
                       2012 - 11 Aug 2012},
      subtyp        = {Other},
      cin          = {ZEL / ZEA-2},
      cid          = {I:(DE-Juel1)ZEL-20090406 / I:(DE-Juel1)ZEA-2-20090406},
      pnm          = {333 - Pathophysiological Mechanisms of Neurological and
                      Psychiatric Diseases (POF2-333) / BMBF-01EZ0822 -
                      NorChloro-Fluoro HomoEpiBatidin (NCFHEB) ein potentieller
                      Positronen-Emission Tomographie-(PET) Marker der frühen
                      Alzheimer-Demenz (BMBF-01EZ0822)},
      pid          = {G:(DE-HGF)POF2-333 / G:(DE-Juel1)BMBF-01EZ0822},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/132106},
}