Molecular MRI Reveals Macrophage‐Enriched Peritumoral Immune Remodeling After Incomplete Ablation in Liver Cancer
ABSTRACT Incomplete image‐guided ablation can promote local tumor progression by reshaping the residual tumor microenvironment toward immunosuppression, yet noninvasive biomarkers of this process remain limited. Here, a translational multiparametric PET/MRI strategy was developed to monitor macrophage‐associated microenvironmental remodeling after incomplete microwave ablation (iMWA) in orthotopic VX2 liver tumors. Twenty‐four tumor‐bearing rabbits were assigned to untreated control, early post‐iMWA (short‐term), or late post‐iMWA (long‐term) groups and underwent clinical 3 T PET/MRI, including diffusion‐weighted imaging, dynamic contrast‐enhanced MRI, [ 1 8 F]FDG PET, and T2‐weighted MRI before and after administration of Eu‐VSOP. Eu‐VSOP‐enhanced MRI revealed a hypointense peritumoral rim after iMWA, with the largest rim‐to‐liver signal decrease and rim thickness observed in the long‐term group. Prussian blue staining and LA‐ICP‐ToF‐MS demonstrated preferential iron and europium enrichment in macrophage‐rich, CD206‐associated peritumoral regions. Histology and proteomics further demonstrated increased CD206 and MMP‐9 expression, extracellular matrix remodeling, immunosuppressive myeloid‐associated changes, and metabolic reprogramming in viable residual tumors, accompanied by altered [ 1 8 F]FDG uptake. Together, these findings indicate that incomplete ablation induces a temporally evolving, macrophage‐rich immunosuppressive peritumoral niche and support the potential of Eu‐VSOP‐enhanced multiparametric PET/MRI for noninvasive monitoring of post‐ablation microenvironmental remodeling.
Authors
- Eyk A. Schellenberger (ORCID: https://orcid.org/0000-0003-4096-6865)
- R Schmidt (ORCID: https://orcid.org/0000-0003-0012-2799)
- Jing Guo (ORCID: https://orcid.org/0000-0002-1170-8157)
- Nikolaus Berndt (ORCID: https://orcid.org/0000-0001-5594-9940)
- Kathrin Textoris‐Taube (ORCID: https://orcid.org/0000-0002-1224-8236)
- Heike Traub (ORCID: https://orcid.org/0000-0001-9937-9476)
- Julian M.M. Rogasch (ORCID: https://orcid.org/0000-0002-0817-6532)
- Nicola Beindorff (ORCID: https://orcid.org/0000-0001-9126-3356)
- Yubei He (ORCID: https://orcid.org/0000-0001-6224-2441)
- Avan Kader (ORCID: https://orcid.org/0000-0002-5453-1267)
- Michael Mülleder (ORCID: https://orcid.org/0000-0001-9792-3861)
- Friederike Hesse (ORCID: https://orcid.org/0000-0001-5427-7564)
- Frank Hofheinz (ORCID: https://orcid.org/0000-0001-8016-4643)
- Lynn Jeanette Savic (ORCID: https://orcid.org/0000-0003-2115-6728)
- Dominik N. Müller (ORCID: https://orcid.org/0000-0003-3650-5644)
- Mathias Schannor (ORCID: https://orcid.org/0000-0003-2990-1331)
- Yu Liu (ORCID: https://orcid.org/0009-0004-2581-1819)
- Luisa Heidemann
- Ralf Hauptmann
- Bernd K. Hamm
- Justus Ramtke (ORCID: https://orcid.org/0009-0009-6010-8340)
- Han Xu (ORCID: https://orcid.org/0009-0000-8119-1475)
- Akvile Häckel (ORCID: https://orcid.org/0009-0001-7398-056X)
Institutions
- Federal Institute For Materials Research and Testing (DE)
- Max Delbrück Center (DE)
- Helmholtz-Zentrum Dresden-Rossendorf (DE)
- TUM Klinikum (DE)
- Humboldt-Universität zu Berlin (DE)
- Berlin Institute of Health at Charité - Universitätsmedizin Berlin (DE)
- German Institute of Human Nutrition (DE)
- Technical University of Munich (DE)
- Freie Universität Berlin (DE)
- Charité - Universitätsmedizin Berlin (DE)
- Otto-von-Guericke-Universität Magdeburg (DE)
Publication Details
- Journal
- Advanced Science
- Published
- 2026-11-05
- DOI
- https://doi.org/10.1002/advs.78490
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00