MRI-Based Radiomics Reveals Cannabinoid-Associated Tumor Phenotypes in a Murine Breast Cancer Model

Introduction and Aim: Assessment of antitumor activity in preclinical models remains challenging when relying solely on conventional size-based imaging, particularly for complex agents such as cannabinoids, whose biological effects may not translate into early volumetric tumor changes. Cannabinoid formulations, including the synthetic cannabinoid JWH-182, Cannabixir® Medium dried flowers, and Cannabixir® THC full extract, exhibit diverse and potentially subtle effects on tumor biology. Radiomics enables high-throughput extraction of quantitative imaging features that capture intratumoral heterogeneity beyond gross tumor volume. The primary aim of this study was to evaluate the utility of MRI-based radiomics as a sensitive tool for detecting cannabinoid-associated tumor phenotypic modulation in a preclinical breast cancer model. Methods: Orthotopic breast tumors were induced in mice using the 4T1 cell line. Animals received cannabinoid formulations in combination with chemotherapy according to a predefined protocol. Tumor burden was assessed at baseline and post-treatment using ultrasonography and whole-body MRI to calculate tumor doubling time. T1- and T2-weighted MRI datasets were segmented and analyzed using radiomics to extract morphometric and signal-based features. Results: Conventional imaging revealed no significant differences in tumor doubling time between most cannabinoid-treated groups and controls, except for accelerated growth in animals treated with Cannabixir® THC full extract. In contrast, radiomics identified distinct, compound-specific tumor phenotypes, including structural features consistent with reduced aggressiveness, in JWH-182-treated tumors, despite similar volumetric growth patterns. Conclusion: MRI-based radiomics sensitively captures cannabinoid-associated tumor phenotype alterations beyond volumetric assessment, supporting its value as a pharmaco-imaging tool for characterizing treatment-related tumor biology in preclinical oncology.