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024 7 _ |a 1536-1632
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037 _ _ |a DZNE-2026-00076
041 _ _ |a English
082 _ _ |a 570
100 1 _ |a Antons, Melissa J
|0 0000-0002-2668-360X
|b 0
245 _ _ |a [18F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy.
260 _ _ |a Cham
|c 2025
|b Springer Nature Switzerland
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520 _ _ |a 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.
536 _ _ |a 352 - Disease Mechanisms (POF4-352)
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650 _ 7 |a Immunohistochemistry
|2 Other
650 _ 7 |a Immunotherapy
|2 Other
650 _ 7 |a Melanoma
|2 Other
650 _ 7 |a [18F]FDG-PET/CT
|2 Other
650 _ 7 |a Fluorodeoxyglucose F18
|0 0Z5B2CJX4D
|2 NLM Chemicals
650 _ 7 |a CTLA-4 Antigen
|2 NLM Chemicals
650 _ 7 |a B7-H1 Antigen
|2 NLM Chemicals
650 _ 7 |a Immune Checkpoint Inhibitors
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Positron Emission Tomography Computed Tomography
|2 MeSH
650 _ 2 |a Fluorodeoxyglucose F18: chemistry
|2 MeSH
650 _ 2 |a Immunotherapy
|2 MeSH
650 _ 2 |a CTLA-4 Antigen: antagonists & inhibitors
|2 MeSH
650 _ 2 |a CTLA-4 Antigen: immunology
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a B7-H1 Antigen: antagonists & inhibitors
|2 MeSH
650 _ 2 |a B7-H1 Antigen: immunology
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a Melanoma, Experimental: diagnostic imaging
|2 MeSH
650 _ 2 |a Melanoma, Experimental: therapy
|2 MeSH
650 _ 2 |a Melanoma, Experimental: pathology
|2 MeSH
650 _ 2 |a Melanoma, Experimental: immunology
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Immune Checkpoint Inhibitors: therapeutic use
|2 MeSH
650 _ 2 |a Immune Checkpoint Inhibitors: pharmacology
|2 MeSH
700 1 _ |a Kloiber-Langhorst, Sandra
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700 1 _ |a Hirner-Eppeneder, Heidrun
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700 1 _ |a Schaefer, Rebecca
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700 1 _ |a Stueckl, Jennifer
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700 1 _ |a Palumbo, Giovanna
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700 1 _ |a Oos, Rosel
|b 6
700 1 _ |a Herr, Felix L
|b 7
700 1 _ |a Lindner, Simon
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700 1 _ |a Ziegler, Sibylle
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700 1 _ |a Brendel, Matthias
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700 1 _ |a Ricke, Jens
|b 11
700 1 _ |a Werner, Rudolf A
|b 12
700 1 _ |a Heimer, Maurice M
|b 13
700 1 _ |a Cyran, Clemens C
|b 14
773 _ _ |a 10.1007/s11307-025-02056-7
|g Vol. 27, no. 6, p. 1006 - 1014
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|t Molecular imaging & biology
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|y 2025
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