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@ARTICLE{Antons:284041,
      author       = {Antons, Melissa J and Kloiber-Langhorst, Sandra and
                      Hirner-Eppeneder, Heidrun and Schaefer, Rebecca and Stueckl,
                      Jennifer and Palumbo, Giovanna and Oos, Rosel and Herr,
                      Felix L and Lindner, Simon and Ziegler, Sibylle and Brendel,
                      Matthias and Ricke, Jens and Werner, Rudolf A and Heimer,
                      Maurice M and Cyran, Clemens C},
      title        = {[18{F}]{FDG}-{PET}/{CT} {I}maging for {R}esponse
                      {C}haracterisation of {E}xperimental {M}elanomas to
                      {A}nti-{PD}-{L}1/{A}nti-{CTLA}-4 {I}mmunotherapy.},
      journal      = {Molecular imaging $\&$ biology},
      volume       = {27},
      number       = {6},
      issn         = {1536-1632},
      address      = {Cham},
      publisher    = {Springer Nature Switzerland},
      reportid     = {DZNE-2026-00076},
      pages        = {1006 - 1014},
      year         = {2025},
      abstract     = {Immune checkpoint inhibition has shown promising results in
                      malignant melanoma, but not all patients respond equally
                      well, necessitating early, accurate monitoring of
                      immunotherapy response. [18F]FDG-PET/CT aids in
                      characterising therapy response beyond morphology, but
                      validated imaging biomarkers for immunotherapy response
                      remain scarce. This study investigated three-time point
                      [18F]FDG-PET/CT to monitor combined anti-PD-L1/anti-CTLA-4
                      immunotherapy in murine melanoma allografts and compared
                      quantitative in vivo imaging biomarkers with ex vivo
                      biomarkers from multiparametric immunohistochemistry at each
                      time point.Melanoma cells (B16-F10) were injected
                      subcutaneously into C57BL/6 mice (n = 40). Seven days
                      post-inoculation, baseline [18F]FDG-PET/CT was conducted.
                      Animals were randomized into two groups; the therapy group
                      received 5 i.p.-injections of anti-PD-L1/anti-CTLA-4 (20
                      µg/kg) on days 7, 9, 11, 13 and 15 after tumor cell
                      inoculation. The control group received sham treatment.
                      PET/CT was performed at baseline (day 7 post inoculation),
                      follow-up 1(day 13; FU-1) and follow-up 2 (day 19; FU-2).
                      Tumor allografts were harvested at each time point for
                      immunohistochemistry (CD8, Ki-67, TUNEL) to validate imaging
                      parameters (MTV, SUVmax).At FU-1, the therapy group
                      exhibited significantly lower MTV than the control group (p
                      = 0.004). At FU-2, MTV and SUVmax were significantly lower
                      (MTV: p = 0.008; SUVmax: p = 0.0003) compared to controls.
                      Ex vivo analysis revealed significant anti-tumor effects in
                      the therapy group, with higher apoptosis rates (FU-1: p =
                      0.012; FU-2: p = 0.001), more CD8-positive T-cells (FU-2: p
                      = 0.003) and lower tumor cell proliferation (FU-1: p =
                      0.012; FU-2: p = 0.012).Multi-time point [18F]FDG-PET/CT
                      allowed for early non-invasive monitoring of combined
                      anti-PD-L1/anti-CTLA-4 immunotherapy in experimental
                      melanomas, validated by multiparametric immunohistochemistry
                      with significant pro-immunogenic, pro-apoptotic and
                      anti-proliferative effects.},
      keywords     = {Animals / Positron Emission Tomography Computed Tomography
                      / Fluorodeoxyglucose F18: chemistry / Immunotherapy / CTLA-4
                      Antigen: antagonists $\&$ inhibitors / CTLA-4 Antigen:
                      immunology / Mice, Inbred C57BL / B7-H1 Antigen: antagonists
                      $\&$ inhibitors / B7-H1 Antigen: immunology / Cell Line,
                      Tumor / Melanoma, Experimental: diagnostic imaging /
                      Melanoma, Experimental: therapy / Melanoma, Experimental:
                      pathology / Melanoma, Experimental: immunology / Mice /
                      Female / Immune Checkpoint Inhibitors: therapeutic use /
                      Immune Checkpoint Inhibitors: pharmacology /
                      Immunohistochemistry (Other) / Immunotherapy (Other) /
                      Melanoma (Other) / [18F]FDG-PET/CT (Other) /
                      Fluorodeoxyglucose F18 (NLM Chemicals) / CTLA-4 Antigen (NLM
                      Chemicals) / B7-H1 Antigen (NLM Chemicals) / Immune
                      Checkpoint Inhibitors (NLM Chemicals)},
      cin          = {AG Haass},
      ddc          = {570},
      cid          = {I:(DE-2719)1110007},
      pnm          = {352 - Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:41102571},
      doi          = {10.1007/s11307-025-02056-7},
      url          = {https://pub.dzne.de/record/284041},
}