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@ARTICLE{Sharma:277137,
      author       = {G. Sharma and M. C. Braga and C. Da Pieve and W. Szopa and
                      T. Starzetz$^*$ and K. H. Plate$^*$ and W. Kaspera and G.
                      Kramer-Marek},
      title        = {{I}mmuno-{PET} {I}maging of {T}umour {PD}-{L}1 {E}xpression
                      in {G}lioblastoma.},
      journal      = {Cancers},
      volume       = {15},
      number       = {12},
      issn         = {2072-6694},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2023-01299},
      pages        = {3131},
      year         = {2023},
      abstract     = {There is no established method to assess the PD-L1
                      expression in brain tumours. Therefore, we investigated the
                      suitability of affibody molecule (ZPD-L1) radiolabelled with
                      F-18 (Al18F) and Ga-68 to measure the expression of PD-L1 in
                      xenograft mouse models of GBM. Mice bearing subcutaneous and
                      orthotopic tumours were imaged 1 h post-radioconjugate
                      administration. Ex vivo biodistribution studies and
                      immunohistochemistry (IHC) staining were performed. Tumoural
                      PD-L1 expression and CD4+/CD8+ tumour-infiltrating
                      lymphocytes were evaluated in human GBM specimens. ZPD-L1
                      was radiolabelled with radiochemical yields of 32.2 ±
                      $4.4\%$ (F-18) and 73.3 ± $1.8\%$ (Ga-68). The
                      cell-associated radioactivity in vitro was consistent with
                      PD-L1 expression levels assessed with flow cytometry. In
                      vivo imaging demonstrated that 18F-AlF-NOTA-ZPD-L1 can
                      distinguish between PD-L1 high-expressing tumours
                      (U87-MGvIII) and PD-L1-negative ones (H292PD-L1Ko). The
                      radioconjugate was quickly cleared from the blood and normal
                      tissues, allowing for high-contrast images of brain tumours
                      as early as 1 h post-injection. 68Ga-NOTA-ZPD-L1 showed
                      heterogeneous and diffuse accumulation that corresponded to
                      the extensively infiltrating GCGR-E55 tumours involving
                      contiguous lobes of the brain. Lastly, $39\%$ of analysed
                      GBM patient samples showed PD-L1+ staining of tumour cells
                      that was associated with elevated levels of CD4+ and CD8+
                      lymphocytes. Our results suggest that the investigated
                      radioconjugates are very promising agents with the potential
                      to facilitate the future design of treatment regimens for
                      GBM patients.},
      keywords     = {PD-L1 (Other) / affibody molecule (Other) / glioblastoma
                      (Other) / immuno-PET (Other)},
      cin          = {FM01},
      ddc          = {610},
      cid          = {I:(DE-He78)FM01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:37370741},
      doi          = {10.3390/cancers15123131},
      url          = {https://inrepo02.dkfz.de/record/277137},
}