Noninvasive molecular imaging signatures of histopathological growth patterns in colorectal cancer liver metastases

Colorectal cancer liver metastases (CRLM) are characterized by distinct histopathological growth patterns (HGPs), desmoplastic (dHGP) also called encapsulated, replacement (rHGP) and pushing (pHGP) types, which have major prognostic and therapeutic implications. HGPs can only be determined histologically after surgical resection. This review explores molecular imaging as a potential in vivo approach to predict and characterize HGPs non-invasively. Based on the biological hallmarks of each pattern regarding glucose metabolism, angiogenesis, hypoxia, fibrotic stromal activation and immune contexture, we outline how specific PET tracers can capture these features. [¹⁸F]FDG PET reflects glycolytic activity; angiogenesis-specific tracers such as arginine-glycine-aspartic acid (RGD) peptides targeting integrins or VEGF-based agents may reflect the neovascularization typical of dHGP. Hypoxia PET may detect oxygen-deprived tumour regions. Fibroblast activation protein inhibitor (FAPI) tracers provide a quantitative marker of fibrotic stromal encapsulation, and immune PET may help distinguish between immune-active dHGP lesions and immune-cold rHGP types. These proposed molecular imaging signatures provide a biologically informed framework for the non-invasive HGPs characterization but remain hypothesis-generating and require prospective translational and clinical validation.