Molecular imaging guided precision radiotherapy and quantitative assessment of metastatic colorectal cancer

Early detection and intervention of metastasis remain challenging and contribute significantly to cancer mortality. This study developed a molecular image-guided precision radiotherapy system that can early detect, precisely irradiate, and quantitatively assess metastatic tumors. Using the highly aggressive orthotopic HCT116 colorectal cancer model, we validated the system's detection sensitivity for primary and metastatic tumors and the efficacy of BLT/CT-guided radiotherapy (32 Gy in 4 fractions). The system detected metastatic tumors as small as 300 μm, with BLT-derived tumor size strongly correlating with histopathology (R² = 0.91, p < 0.001). gamma-H2AX immunofluorescence staining revealed DNA damage foci predominantly localized within the tumor volume, confirming precise targeting. At 23 days post-treatment, the irradiation group exhibited reduction in bioluminescence intensity to 0.61-fold and tumor volume to 0.57-fold of initial values, whereas the control group showed increases to 86.62-fold and 5.89-fold, respectively (p < 0.001). FITC-dextran permeability assay and histological analysis of the entire intestine confirmed preserved intestinal barrier function and structural integrity. With precise targeting and minimal toxicity, the radiation group achieved >2-fold prolonged survival. This multimodal image-guided system enables accurate localization, precise treatment, and quantitative assessment of early-stage and metastatic tumors, offering significant potential for malignancies within complex soft tissue environments or with disseminated spread.