TY  - JOUR
AU  - Antons, Melissa J
AU  - Kloiber-Langhorst, Sandra
AU  - Hirner-Eppeneder, Heidrun
AU  - Schaefer, Rebecca
AU  - Stueckl, Jennifer
AU  - Palumbo, Giovanna
AU  - Oos, Rosel
AU  - Herr, Felix L
AU  - Lindner, Simon
AU  - Ziegler, Sibylle
AU  - Brendel, Matthias
AU  - Ricke, Jens
AU  - Werner, Rudolf A
AU  - Heimer, Maurice M
AU  - Cyran, Clemens C
TI  - [18F]FDG-PET/CT Imaging for Response Characterisation of Experimental Melanomas to Anti-PD-L1/Anti-CTLA-4 Immunotherapy.
JO  - Molecular imaging & biology
VL  - 27
IS  - 6
SN  - 1536-1632
CY  - Cham
PB  - Springer Nature Switzerland
M1  - DZNE-2026-00076
SP  - 1006 - 1014
PY  - 2025
AB  - 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.
KW  - Animals
KW  - Positron Emission Tomography Computed Tomography
KW  - Fluorodeoxyglucose F18: chemistry
KW  - Immunotherapy
KW  - CTLA-4 Antigen: antagonists & inhibitors
KW  - CTLA-4 Antigen: immunology
KW  - Mice, Inbred C57BL
KW  - B7-H1 Antigen: antagonists & inhibitors
KW  - B7-H1 Antigen: immunology
KW  - Cell Line, Tumor
KW  - Melanoma, Experimental: diagnostic imaging
KW  - Melanoma, Experimental: therapy
KW  - Melanoma, Experimental: pathology
KW  - Melanoma, Experimental: immunology
KW  - Mice
KW  - Female
KW  - Immune Checkpoint Inhibitors: therapeutic use
KW  - Immune Checkpoint Inhibitors: pharmacology
KW  - Immunohistochemistry (Other)
KW  - Immunotherapy (Other)
KW  - Melanoma (Other)
KW  - [18F]FDG-PET/CT (Other)
KW  - Fluorodeoxyglucose F18 (NLM Chemicals)
KW  - CTLA-4 Antigen (NLM Chemicals)
KW  - B7-H1 Antigen (NLM Chemicals)
KW  - Immune Checkpoint Inhibitors (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41102571
DO  - DOI:10.1007/s11307-025-02056-7
UR  - https://pub.dzne.de/record/284041
ER  -