Journal Article

DZNE-2026-00076

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png [18F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy.

Antons, M. J. ; Kloiber-Langhorst, S. ; Hirner-Eppeneder, H. ; Schaefer, R. ; Stueckl, J. ; Palumbo, G. ; Oos, R. ; Herr, F. L. ; Lindner, S. ; Ziegler, S. ; Brendel, M.DZNE* ; Ricke, J. ; Werner, R. A. ; Heimer, M. M. ; Cyran, C. C.

2025
Springer Nature Switzerland Cham

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Please use a persistent id in citations: doi:10.1007/s11307-025-02056-7

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.

Keyword(s): Animals (MeSH) ; Positron Emission Tomography Computed Tomography (MeSH) ; Fluorodeoxyglucose F18: chemistry (MeSH) ; Immunotherapy (MeSH) ; CTLA-4 Antigen: antagonists & inhibitors (MeSH) ; CTLA-4 Antigen: immunology (MeSH) ; Mice, Inbred C57BL (MeSH) ; B7-H1 Antigen: antagonists & inhibitors (MeSH) ; B7-H1 Antigen: immunology (MeSH) ; Cell Line, Tumor (MeSH) ; Melanoma, Experimental: diagnostic imaging (MeSH) ; Melanoma, Experimental: therapy (MeSH) ; Melanoma, Experimental: pathology (MeSH) ; Melanoma, Experimental: immunology (MeSH) ; Mice (MeSH) ; Female (MeSH) ; Immune Checkpoint Inhibitors: therapeutic use (MeSH) ; Immune Checkpoint Inhibitors: pharmacology (MeSH) ; Immunohistochemistry ; Immunotherapy ; Melanoma ; [18F]FDG-PET/CT ; Fluorodeoxyglucose F18 ; CTLA-4 Antigen ; B7-H1 Antigen ; Immune Checkpoint Inhibitors

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Contributing Institute(s):

1. Molecular Neurodegeneration (AG Haass)

Research Program(s):

1. 352 - Disease Mechanisms (POF4-352) (POF4-352)

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Database coverage:
; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Springer ; DEAL Springer ; Ebsco Academic Search ; Essential Science Indicators ; IF < 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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