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000284041 037__ $$aDZNE-2026-00076
000284041 041__ $$aEnglish
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000284041 1001_ $$00000-0002-2668-360X$$aAntons, Melissa J$$b0
000284041 245__ $$a[18F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy.
000284041 260__ $$aCham$$bSpringer Nature Switzerland$$c2025
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000284041 520__ $$aImmune 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.
000284041 536__ $$0G:(DE-HGF)POF4-352$$a352 - Disease Mechanisms (POF4-352)$$cPOF4-352$$fPOF IV$$x0
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000284041 650_7 $$2Other$$aImmunohistochemistry
000284041 650_7 $$2Other$$aImmunotherapy
000284041 650_7 $$2Other$$aMelanoma
000284041 650_7 $$2Other$$a[18F]FDG-PET/CT
000284041 650_7 $$00Z5B2CJX4D$$2NLM Chemicals$$aFluorodeoxyglucose F18
000284041 650_7 $$2NLM Chemicals$$aCTLA-4 Antigen
000284041 650_7 $$2NLM Chemicals$$aB7-H1 Antigen
000284041 650_7 $$2NLM Chemicals$$aImmune Checkpoint Inhibitors
000284041 650_2 $$2MeSH$$aAnimals
000284041 650_2 $$2MeSH$$aPositron Emission Tomography Computed Tomography
000284041 650_2 $$2MeSH$$aFluorodeoxyglucose F18: chemistry
000284041 650_2 $$2MeSH$$aImmunotherapy
000284041 650_2 $$2MeSH$$aCTLA-4 Antigen: antagonists & inhibitors
000284041 650_2 $$2MeSH$$aCTLA-4 Antigen: immunology
000284041 650_2 $$2MeSH$$aMice, Inbred C57BL
000284041 650_2 $$2MeSH$$aB7-H1 Antigen: antagonists & inhibitors
000284041 650_2 $$2MeSH$$aB7-H1 Antigen: immunology
000284041 650_2 $$2MeSH$$aCell Line, Tumor
000284041 650_2 $$2MeSH$$aMelanoma, Experimental: diagnostic imaging
000284041 650_2 $$2MeSH$$aMelanoma, Experimental: therapy
000284041 650_2 $$2MeSH$$aMelanoma, Experimental: pathology
000284041 650_2 $$2MeSH$$aMelanoma, Experimental: immunology
000284041 650_2 $$2MeSH$$aMice
000284041 650_2 $$2MeSH$$aFemale
000284041 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: therapeutic use
000284041 650_2 $$2MeSH$$aImmune Checkpoint Inhibitors: pharmacology
000284041 7001_ $$aKloiber-Langhorst, Sandra$$b1
000284041 7001_ $$aHirner-Eppeneder, Heidrun$$b2
000284041 7001_ $$aSchaefer, Rebecca$$b3
000284041 7001_ $$aStueckl, Jennifer$$b4
000284041 7001_ $$aPalumbo, Giovanna$$b5
000284041 7001_ $$aOos, Rosel$$b6
000284041 7001_ $$aHerr, Felix L$$b7
000284041 7001_ $$aLindner, Simon$$b8
000284041 7001_ $$aZiegler, Sibylle$$b9
000284041 7001_ $$0P:(DE-2719)9001539$$aBrendel, Matthias$$b10$$udzne
000284041 7001_ $$aRicke, Jens$$b11
000284041 7001_ $$aWerner, Rudolf A$$b12
000284041 7001_ $$aHeimer, Maurice M$$b13
000284041 7001_ $$aCyran, Clemens C$$b14
000284041 773__ $$0PERI:(DE-600)2079211-6$$a10.1007/s11307-025-02056-7$$gVol. 27, no. 6, p. 1006 - 1014$$n6$$p1006 - 1014$$tMolecular imaging & biology$$v27$$x1536-1632$$y2025
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