Lipidomic Profiling of Rabbit VX2 Tumors Using Matrix-assisted Laser Desorption Ionization Mass Spectrometry Imaging

Purpose To characterize lipidomic profiles in the VX2 rabbit tumor model and assess potential lipid plasticity across tumor microenvironments in the liver and flank. Materials and Methods VX2 tumors were implanted into the liver in four rabbits and both flanks in two rabbits. After 10-14 days, tumor-containing tissues were harvested, snap frozen, sectioned, and analyzed using matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) in both positive and negative ion modes. Tandem mass spectrometry was used for further characterization. Lipid identities were determined based on accurate mass, fragmentation patterns, and database matching. Molecular ion distributions were spatially correlated with hematoxylin-eosin-stained sections. Results MALDI-MSI revealed distinct lipidomic profiles between liver and flank tumors. Oleate (mass-to-charge ratio [m/z] 281.24) was consistently localized to viable tumor regions in both sites. Phosphatidic acid 18:0/18:1(m/z 701.51) was detected in only liver tumors, whereas phosphatidylinositol 18:2/18:0 (m/z 861.55) was prominent in flank tumors but absent from liver tumors, despite being present in surrounding healthy parenchyma. Phosphatidylcholine (PC) species, notably PC 34:1 (m/z 798.52) and PC 36:2 (m/z 808.56), and PC (P-36:2) (m/z 824.56), showed heterogeneous spatial distributions across both anatomic sites. Conclusion MALDI-MSI enabled spatial mapping of lipid distributions within VX2 tumors, revealing both shared and site-specific alterations. These findings reveal heterogeneous spatial lipid distributions in the VX2 model and may reflect microenvironment-driven lipid plasticity. Keywords: Mass Spectrometry Imaging, VX2 Rabbit Tumor Model, Lipidomic Profiles, Ablation Techniques © RSNA 2026.