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@INPROCEEDINGS{Becker:132104,
      author       = {Becker, G and Wilke, S and Schönknecht, P and Patt, M and
                      Luthardt, J and Hesse, S and Wagenknecht, Gudrun and
                      Höpping, A and Brust, P and Sabri, O},
      title        = {{PET} {Q}uantification {O}f 18{F}-{F}lubatine {B}inding
                      {T}o {N}icotinic alpha4beta2 acetylcholine receptors in
                      {H}uman {B}rains},
      reportid     = {FZJ-2013-01343},
      year         = {2012},
      abstract     = {Objectives: Nicotinic alpha4beta2 acetylcholine receptors
                      (nAChR) are an important target for diagnostic neuroimaging
                      because of their involvement in Alzheimer's disease (AD) and
                      Parkinson's disease. Using 2-[18F]F-A85380 PET a significant
                      decline in alpha4beta2-nAChRs in early AD-patients which
                      correlated to loss of cognitive function was shown (1, 2).
                      However, this tracer is not suited for use as biomarker for
                      early AD-diagnosis in a routine clinical set-up because of
                      its unfavourable slow kinetics. Here we used the new
                      radiotracer (-)-[18F]-Flubatine (formerly (-)-[18F]-NCFHEB)
                      with significantly improved brain uptake, receptor affinity
                      and selectivity (3). nAChR-parameters were determined by
                      full kinetic modeling and the validity of the practically
                      useful tissue ratio and tissue-to-plasma ratio as receptor
                      parameters was evaluated. Methods: After intravenous
                      administration of ~370 MBq (-)-[18F]-Flubatine, the PET
                      brain imaging was performed in 20 healthy controls (age
                      70.6±4.6) using an ECAT EXACT HR+ system in 3D-acquisition
                      mode. 23 frames were acquired from 0-90 min post injection
                      and motion corrected with SPM2. Kinetic modeling using a
                      1-tissue compartment model (1TCM) with arterial
                      input-function was applied to the volume of interest (VOI)
                      based tissue-activity curves (TACs) generated for 29 brain
                      regions (anatomically defined via MRI co-registration).
                      Model-based receptor parameters used were the total
                      distribution volume (VT) and the distribution volume ratio
                      (DVR) (reference: posterior corpus callosum). In addition
                      the standardized uptake value ratio (SUVR) (50-70 min) as
                      approximation of the DVR and the tissue-to-plasma
                      concentration ratio (TTPR) (70-90 min) as approximation of
                      VT were used as non model-based receptor parameters.
                      Results: TACs of all 29 regions could be described
                      adequately with the 1TCM and all kinetic parameters could be
                      reliably estimated from 90 min PET data. VT increased as
                      expected with receptor density. Corpus callosum (VT:
                      5.68±1.01), frontal cortex (9.18±0.59), parietal cortex
                      (9.10±0.61), pons (11.10±0.86), thalamus (25.03±3.33).
                      Mean TTPR values in frontal and parietal cortices were $2\%$
                      higher than the corresponding VT values but $7\%$ lower in
                      the thalamus. There was a strong linear correlation between
                      the two sets of TTPR and VT values (r2 = 0.98, p < 10-4)
                      (Fig. 1A). As VT, DVR increased with receptor density.
                      Frontal cortex (DVR: 1.66±0.27), parietal cortex
                      (1.64±0.27), pons (2.01±0.35), thalamus (4.52±0.87). Mean
                      SUVR values in frontal and parietal cortices were almost
                      identical to mean DVR values (difference $<0.1\%)$ but ~15
                      $\%$ lower in the thalamus. Accordingly there was a strong
                      linear correlation between the SUVR and DVR values (r2 =
                      0.97, p < 10-4) (Fig. 1B). Conclusions: For
                      (-)-[18F]-Flubatine the receptor parameters TTPR and SUVR in
                      cortical regions are in excellent agreement with
                      corresponding parameters computed by full kinetic modeling.
                      For unbiased estimates of TTPR and SUVR in the thalamus the
                      use of a bolus/infusion scheme for tracer application should
                      be considered. References: 1. O. Sabri, ..P. Brust:
                      Acetylcholine receptors in dementia and mild cognitive
                      impairment. Eur J Nucl Med Mol Imaging 2008; 35 (Suppl. 1):
                      30-45. 2. K. Kendziorra, ..O. Sabri: Decreased cerebral
                      a4ß2 nicotinic acetylcholine receptors in living patients
                      with mild cognitive impairment and Alzheimer's disease
                      assessed with positron emission tomography. Eur J Nucl Med
                      Mol Imaging 2010; 38: 515-525. 3. P. Brust, ..O. Sabri:
                      In-vivo measurement of nicotinic acetylcholine receptors
                      with [18 F]norchloro-fluoro-homoepibatidine (NCFHEB).
                      Synapse 2008; 62: 205-218. Linear regression analysis. (A)
                      Tissue-to-plasma concentration ratio (TTPR) and total
                      distribution volume (VT). (B) Standardized uptake value
                      ratio (SUVR) and distribution volume ratio (DVR).},
      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/132104},
}