%0 Journal Article
%A Antons, Melissa J
%A Kloiber-Langhorst, Sandra
%A Hirner-Eppeneder, Heidrun
%A Schaefer, Rebecca
%A Stueckl, Jennifer
%A Palumbo, Giovanna
%A Oos, Rosel
%A Herr, Felix L
%A Lindner, Simon
%A Ziegler, Sibylle
%A Brendel, Matthias
%A Ricke, Jens
%A Werner, Rudolf A
%A Heimer, Maurice M
%A Cyran, Clemens C
%T [18F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy.
%J Molecular imaging & biology
%V 27
%N 6
%@ 1536-1632
%C Cham
%I Springer Nature Switzerland
%M DZNE-2026-00076
%P 1006 - 1014
%D 2025
%X 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.
%K Animals
%K Positron Emission Tomography Computed Tomography
%K Fluorodeoxyglucose F18: chemistry
%K Immunotherapy
%K CTLA-4 Antigen: antagonists & inhibitors
%K CTLA-4 Antigen: immunology
%K Mice, Inbred C57BL
%K B7-H1 Antigen: antagonists & inhibitors
%K B7-H1 Antigen: immunology
%K Cell Line, Tumor
%K Melanoma, Experimental: diagnostic imaging
%K Melanoma, Experimental: therapy
%K Melanoma, Experimental: pathology
%K Melanoma, Experimental: immunology
%K Mice
%K Female
%K Immune Checkpoint Inhibitors: therapeutic use
%K Immune Checkpoint Inhibitors: pharmacology
%K Immunohistochemistry (Other)
%K Immunotherapy (Other)
%K Melanoma (Other)
%K [18F]FDG-PET/CT (Other)
%K Fluorodeoxyglucose F18 (NLM Chemicals)
%K CTLA-4 Antigen (NLM Chemicals)
%K B7-H1 Antigen (NLM Chemicals)
%K Immune Checkpoint Inhibitors (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:41102571
%R 10.1007/s11307-025-02056-7
%U https://pub.dzne.de/record/284041