Molecular MRI Reveals Macrophage‐Enriched Peritumoral Immune Remodeling After Incomplete Ablation in Liver Cancer
Yubei He, Han Xu, Julian M. M. Rogasch, Nikolaus Berndt, Jing Guo, Eyk Schellenberger, Akvile Häckel, Luisa Heidemann, Friederike Hesse, Yu Liu, Justus Ramtke, Nicola Beindorff, Frank Hofheinz, Avan Kader, Michael Mülleder, Kathrin Textoris‐Taube, Bernd Hamm, Dominik N. Müller, Robin Schmidt, Ralf Hauptmann, Heike Traub, Mathias Schannor, Lynn Jeanette SavicABSTRACT
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.