Radium-223 dichloride is a radiopharmaceutical used to treat cancer that has metastasized to the bones, and whose effects are derived from both direct action of radiation on tumor cells as well as bystander effects caused by irradiation of both tumor and non-tumor cells in the bone microenvironment. Here, Canter and colleagues quantify the biological effects derived from both of these mechanisms of action. Direct effects from alpha particle irradiation (yellow arrows in the image at left) contribute to biological changes detected histologically in disseminated tumor cells and osteocytes within the range of the alpha particles. Bystander effects also contribute to biological changes in tumor cells beyond the range of the alpha particles emitted from the endosteal surface of the bone. These radiation-induced bystander effects can arise from tumor cells (white outlined arrow) and marrow cells (pink outlined arrow) within the range of alpha particles, and from bone cells (brown outlined...

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