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@ARTICLE{Schaefer:302833,
      author       = {R. Schaefer and L. H. Kunze and M. Haertel and Y. Zhu and
                      K. Schlepckow and M. Willem and L. M. Bartos and G. Palumbo
                      and L. Tomas and C. Schulz and S. Massberg and R. A. Werner
                      and M. Fischer and D. Xia and K. M. Monroe and C. Haass and
                      M. Brendel$^*$ and S. Lindner},
      title        = {{I}mage-{D}erived {B}lood {N}ormalization of
                      {A}ntibody-{B}ased {TREM}2 {PET} in {M}ouse {M}odels of
                      {A}myloidosis and {M}yocardial {I}nfarction.},
      journal      = {Journal of nuclear medicine},
      volume       = {66},
      number       = {9},
      issn         = {0097-9058},
      address      = {New York, NY},
      publisher    = {Soc.},
      reportid     = {DKFZ-2025-01373},
      pages        = {1419-1424},
      year         = {2025},
      note         = {2025 Sep 2;66(9):1419-1424},
      abstract     = {The triggering receptor expressed on myeloid cells 2
                      (TREM2) plays a pivotal role in the activation of myeloid
                      cells and is currently being investigated as a potential
                      therapeutic target in several diseases. In this study, we
                      established enhanced quantification of PET images of a
                      64Cu-labeled antibody-based PET radiotracer as a noninvasive
                      tool for the assessment of TREM2 expression in the brain and
                      peripheral organs of mice. We used TREM2 knockout mice that
                      lack target expression to investigate data-driven blood
                      normalization of PET images against percentage of injected
                      dose normalization. Methods: TREM2 knockout and wild-type
                      mice (n = 11 each) were injected with the radiotracer
                      [64Cu]Cu-NODAGA-ATV:4D9 (ATV is antibody transport vehicle).
                      Twenty hours after injection, TREM2 PET was conducted and
                      blood samples were collected. A voxelwise analysis with
                      statistical parametric mapping served to determine voxels
                      that correlate with ex vivo blood radioactivity levels.
                      Furthermore, TREM2 PET signals were compared between mice
                      with and those without TREM2 expression using image-derived
                      blood normalization. Correlation with TREM2 protein
                      expression levels in the lung, liver, spleen, and bone
                      marrow was used to validate organ-specific PET results.
                      Disease models of brain amyloidosis and myocardial
                      infarction were investigated to test for the value of
                      image-derived normalization in mice. Results: Blood
                      radioactivity levels derived from a statistical parametric
                      mapping-derived region of interest demonstrated a robust
                      correlation with radioactivity measurements obtained from ex
                      vivo blood samples. Voxelwise clusters of TREM2 PET signals
                      were more robustly detected after blood normalization of the
                      PET images. Significant voxelwise clusters of TREM2 PET
                      signals in peripheral organs correlated with TREM2 protein
                      expression levels. Furthermore, image-derived normalization
                      enhanced the significance of voxelwise clusters of TREM2 in
                      the brains of App SAA;TfRmu/hu mice, as well as the TREM2
                      signal in the myocardial infarct region. Both strongly
                      correlated with ex vivo autoradiography. Conclusion:
                      Normalization of PET images to account for blood levels
                      enhanced the detection of TREM2. This improved methodology
                      for TREM2 PET analysis provides a promising basis for future
                      assessments of TREM2 imaging.},
      keywords     = {64Cu (Other) / ATV:4D9 (Other) / PET (Other) / SPM (Other)
                      / TREM2 (Other)},
      cin          = {MU01},
      ddc          = {610},
      cid          = {I:(DE-He78)MU01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:40639905},
      doi          = {10.2967/jnumed.125.269472},
      url          = {https://inrepo02.dkfz.de/record/302833},
}