Effect of intratumoral alpha radiation on tumor growth delay and tumor microenvironment in an orthotopic colorectal liver metastasis murine model.

Colorectal cancer frequently spreads to the liver, and current treatments often damage healthy liver tissue, while targeting tumors. Diffusing Alpha-emitters Radiation Therapy (Alpha DaRT) disperses alpha-emitting atoms from an intra-tumoral implanted source to a range of a few millimeters in the tumor. Alpha radiation is highly efficient in killing cancer cells, compared to other radiation types, and its short range in the tissue, potentially enables sparing healthy tissue adjacent to the tumor. Alpha DaRT's efficacy was previously demonstrated in subcutaneous tumors from various histotypes. Yet its effectiveness in treating tumors located in an internal organ, such as the liver, remains to be tested in animal studies. Here, we used a single liver metastasis orthotopic model by implanting MC38 colorectal metastatic tissue in mice livers. The metastasis was then treated either with a single radioactive or inert Alpha-DaRT source. Alpha-DaRT effectively delayed tumor growth without damaging the surrounding liver parenchymal tissue. F4/80 + immunosuppressive macrophages in the tumor-normal tissue interface were reduced following treatment. The findings suggest that this type of radiation therapy could be a promising option for treating patients with liver tumors.