Molecular MRI Reveals Macrophage‐Enriched Peritumoral Immune Remodeling After Incomplete Ablation in Liver Cancer
14 affiliations
- 1Department of Radiology Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt – Universität zu Berlin Berlin Germany
- 2Experimental and Clinical Research Center (ECRC) A Cooperation of Charité – Universitätsmedizin Berlin and Max Delbrück Center for Molecular Medicine (MDC) Berlin Germany
- 3Department of Nuclear Medicine Campus Virchow‐Klinikum Charité‐Universitätsmedizin Berlin Berlin Germany
- 4Department of Molecular Toxicology German Institute of Human Nutrition Potsdam – Rehbruecke (DIfE) Nuthetal Germany
- 5Berlin Institute of Health at Charité – Universitätsmedizin Berlin Berlin Germany
- 6Berlin Experimental Radionuclide Imaging Center (BERIC, RRID: SCR_028573) Charité Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt Universität zu Berlin Berlin Germany
- 7Helmholtz – Zentrum Dresden – Rossendorf, PET Center Institute of Radiopharmaceutical Cancer Research Dresden Germany
- 8Department of Diagnostic and Interventional Radiology Technical University of Munich Munich Germany
- 9Core Facility High – Throughput Mass Spectrometry Charité – Universitätsmedizin Berlin Freie Universität Berlin and Humboldt – Universität zu Berlin Berlin Germany
- 10Charité – Universitätsmedizin Berlin Corporate Member of Freie Universität Berlin and Humboldt – Universität zu Berlin Berlin Germany
- 11Max Delbrück Center for Molecular Medicine in the Helmholtz Association Berlin Germany
- 12Bundesanstalt für Materialforschung und – prüfung (BAM) Berlin Germany
- 13Freie Universität Berlin Institute of Geological Sciences Berlin Germany
- 14Department of Radiology and Nuclear Medicine Otto – von – Guericke University Magdeburg Magdeburg Germany
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 8F]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 8F]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.
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BibTeX
@article{he2026molecular,
title = {{Molecular MRI Reveals Macrophage‐Enriched Peritumoral Immune Remodeling After Incomplete Ablation in Liver Cancer}},
author = {Yubei He and Han Xu and Julian M. M. Rogasch and Nikolaus Berndt and Jing Guo and Eyk Schellenberger and Akvile Häckel and Luisa Heidemann and Friederike Hesse and Yu Liu and Justus Ramtke and Nicola Beindorff and Frank Hofheinz and Avan Kader and Michael Mülleder and Kathrin Textoris‐Taube and Bernd Hamm and Dominik N. Müller and Robin Schmidt and Ralf Hauptmann and Heike Traub and Mathias Schannor and Lynn Jeanette Savic},
journal = {Advanced Science},
year = {2026},
month = nov,
doi = {10.1002/advs.78490},
url = {https://doi.org/10.1002/advs.78490},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Molecular MRI Reveals Macrophage‐Enriched Peritumoral Immune Remodeling After Incomplete Ablation in Liver Cancer
AU - Yubei He
AU - Han Xu
AU - Julian M. M. Rogasch
AU - Nikolaus Berndt
AU - Jing Guo
AU - Eyk Schellenberger
AU - Akvile Häckel
AU - Luisa Heidemann
AU - Friederike Hesse
AU - Yu Liu
AU - Justus Ramtke
AU - Nicola Beindorff
AU - Frank Hofheinz
AU - Avan Kader
AU - Michael Mülleder
AU - Kathrin Textoris‐Taube
AU - Bernd Hamm
AU - Dominik N. Müller
AU - Robin Schmidt
AU - Ralf Hauptmann
AU - Heike Traub
AU - Mathias Schannor
AU - Lynn Jeanette Savic
PY - 2026
DA - 2026/11/05
JO - Advanced Science
DO - 10.1002/advs.78490
UR - https://doi.org/10.1002/advs.78490
AB - 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 8F]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 8F]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.
SN - 2198-3844
ER -