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@INPROCEEDINGS{Foerges:1009675,
      author       = {Foerges, Anna Linea and Kroll, Tina and Matusch, Andreas
                      and Neumaier, Bernd and Bauer, Andreas and Drzezga,
                      Alexander and Elmenhorst, David},
      title        = {{Q}uantification of [18{F}]-{S}yn{V}es{T}-1 {PET} using
                      thin-layer chromatography and image derived input function},
      reportid     = {FZJ-2023-02928},
      year         = {2023},
      abstract     = {Objectives: Synaptic vesicle protein 2A, a marker of
                      synaptic density, can be imaged by [18F]SynVesT 1 positron
                      emission tomography (PET), but quantification requires an
                      arterial input function. An alternative to high-performance
                      liquid chromatography (HPLC) of arterial blood samples can
                      be an input function derived from the dynamic PET images in
                      combination with thin-layer chromatography (TLC)-based
                      analysis of arterialized venous blood. We aimed to quantify
                      synaptic density by obtaining an image derived input
                      function (IDIF) from bilateral internal carotid artery
                      volume of interest (VOI) at the level of the carotid siphon
                      and correcting it for metabolites using a newly developed
                      blood analysis with TLC.Methods: [18F]SynVesT-1 PET list
                      mode (90 min) data and three-dimensional T1-weighted
                      magnetic resonance (MR) data were collected in nine healthy
                      volunteers using an integrated 3 Tesla MR/BrainPET system.
                      Reconstructed PET data (framing schema: 6x 10s, 3x 20s, 3x
                      30s, 4x 60s, 3x 150s, 15x 300s) and corresponding MR data
                      were realigned, co-registered, segmented and normalized
                      using PMOD Neuro Tool. The first eight normalized PET frames
                      were averaged and filtered (6 mm 3D Gaussian), then, based
                      on this PET image, cubic VOIs were placed over the left and
                      right internal carotid arteries. Subsequently, the 20
                      hottest connected voxels within each cubic VOI were
                      automatically selected on each side and merged into one VOI,
                      which was transferred to the dynamic PET images to obtain
                      IDIF. Arterialized venous blood samples were collected
                      repeatedly during the PET scan. For blood analysis, aliquots
                      of plasma (400 µl) were mixed with SynVesT 1 cold standard
                      (20 µl, 5µg/ml) and extraction solution
                      (acetonitrile/methanol, 50/50, 800 µl). The mixture was
                      centrifuged and aliquots of supernatants were applied to a
                      TLC plate and developed with a mobile phase of
                      chloroform/methanol/diethylamine (18.4 ml/1.6 ml/40 µl).
                      Whole blood, plasma and pellets were measured in a
                      γ-counter. TLC plates were developed in a Canberra instant
                      imager for 4 h and analysed with the corresponding software.
                      IDIF was scaled [1] using whole blood samples drawn 60, 75
                      and 90 min after simultaneous injection and scan start to
                      correct for partial volume effects. The scaled IDIF was used
                      to generate a metabolite- and extraction-corrected (derived
                      from blood analysis) plasma input function. These input
                      functions were used to apply the one-tissue compartment
                      model (1TCM) to quantify regional synaptic density in the
                      human brain.Results: Synaptic density was quantified in nine
                      volunteers (4 females) aged 20-45 years (mean: 27.8 ± 9.4)
                      using TLC-based blood analysis, IDIF and the 1TCM. The
                      fraction of radioactivity corresponding to the parent
                      compound was 34 ± 6 $\%$ and 31 ± 5 $\%$ at 60 min and 90
                      min after radiotracer injection, respectively. The scaling
                      factor was 1.27 ± 0.20 on average. Mean [18F]SynVesT 1 VT
                      values ranged from 3.64 ± 21.06 mL/cm³ in the centrum
                      semiovale to 20.90 ± 3.87 ml/cm³ in the Heschl’s gyrus.
                      Estimated K1 ranged from 0.303 ±0.065 ml/min/cm³ (centrum
                      semiovale) to 1.163 ± 0.270 ml/min/cm³ (Heschl’s gyrus)
                      and the k2 estimates ranged from 0.040 ± 0.010 (amygdala)
                      to 0.112 ± 0.024 (pons).Conclusion: The parent fraction of
                      radioactivity at 60 min after radiotracer injection was
                      slightly higher compared to HPLC-based results [2].
                      Estimated VT values were similar to those reported
                      previously [2], whereas K1 and k2 values were higher. Our
                      preliminary data suggest that IDIF with bilateral VOI over
                      the internal carotid artery in combination with TLC-based
                      blood analysis may be an alternative to arterial input
                      functions for quantification of synaptic density using
                      [18F]SynVesT-1 PET in human brains.References:[1] He X. et
                      al. (2020), `Image-derived input functions for
                      quantification of A1 adenosine receptors availability in
                      mice brains using PET and [18F]CPFPX´, Frontiers in
                      Physiology, vol. 29, no. 10, pp. 1617.[2] Naganawa M. et al.
                      (2021), `First-in-human evaluation of (18)F-SynVesT-1, a
                      novel radioligand for PET imaging of synaptic vesicle
                      protein 2A´, Journal of Nuclear Medicine, vol. 62, no. 4,
                      pp. 561-567.},
      month         = {Jul},
      date          = {2023-07-22},
      organization  = {The 29th Annual Meeting of the
                       Organization for Human Brain Mapping,
                       Montréal (Canada), 22 Jul 2023 - 26
                       Jul 2023},
      subtyp        = {After Call},
      cin          = {INM-2 / INM-5},
      cid          = {I:(DE-Juel1)INM-2-20090406 / I:(DE-Juel1)INM-5-20090406},
      pnm          = {5253 - Neuroimaging (POF4-525) / 5252 - Brain Dysfunction
                      and Plasticity (POF4-525) / SleepLess - Darstellung
                      synaptischer Plastizität während therapeutischen
                      Schlafentzugs in Depression (01EW1808)},
      pid          = {G:(DE-HGF)POF4-5253 / G:(DE-HGF)POF4-5252 /
                      G:(BMBF)01EW1808},
      typ          = {PUB:(DE-HGF)24},
      url          = {https://juser.fz-juelich.de/record/1009675},
}