Intratumoral 224Ra-loaded wires spread alpha-emitters inside solid human tumors in athymic mice achieving tumor control.

Abstract

BACKGROUND: We developed a new method of brachytherapy, termed diffusing alpha-emitters radiation therapy (DaRT), based on the use of intratumoral (224)Ra-loaded wires, which release short-lived alpha-emitting atoms by recoil. Here, we examined their ability to destroy and control the development of several human-derived tumors implanted in athymic mice. MATERIALS AND METHODS: The experiments were performed on athymic mice bearing malignant human-derived tumors including prostate (PC-3), glioblastoma (GBM, U87-MG), colon (HCT15), squamous cell carcinoma (FaDu) and melanoma (C32). One or more (224)Ra-loaded wires were inserted into the tumors, and mice were assessed for tumor growth rate and survival. RESULTS: In vivo studies showed that DaRT can effectively destroy the tumors, and in vitro tests confirmed the sensitivity of the studied cells to alpha particles. While the C32 cells were relatively resistant, other tumor types (e.g. HCT15) exhibited sensitivity in both measured aspects. CONCLUSION: DaRT could potentially be combined with chemotherapy or other treatment modalities to effectively treat non-resectable tumors.