Ablation of experimental colon cancer by intratumoral ²²⁴Radium-loaded wires is mediated by alpha particles released from atoms which spread in the tumor and can be augmented by chemotherapy

Abstract

Purpose: We developed ²²⁴Ra-loaded wires, which release by recoil alpha emitting nuclei into solid tumors and cause tumor cell killing. This research examined if the major damage was inflicted by alpha particles emitted from these atoms or by direct gamma and beta emissions from the inserted wires. We also examined the efficacy of this treatment against colon cancer in combination with chemotherapy.

Materials and methods: Mouse colon carcinomas (CT-26 xenografts), treated by intra-tumoral radioactive wires loaded with ²²⁴Ra atoms were monitored for effects on tumor growth, intratumoral tissue damage and distribution of alpha emitting atoms. The effects were compared with those of ²²⁴Ra-loaded wires coated with poly methyl methacrylate (PMMA), which blocks atom recoil. Similar experiments were performed with radioactive wires combined with systemic 5-FU.

Results: ²²⁴Ra-loaded wires inhibited tumor growth and formed necrotic areas inside the tumor. PMMA coated wires did not inhibit tumor growth, and caused minor intratumoral damage. Autoradiography images of tumors treated with ²²⁴Ra-loaded wires revealed a spread of alpha emitters over several mm, whereas PMMA-coated wires showed no such spread. Injection of 5-FU with ²²⁴Ra-loaded wires augmented tumor growth retardation and cure.

Conclusions: ²²⁴Ra-loaded wires ablate solid tumors by the release of alpha-particle emitting atoms inside the tissue, an effect that can be enhanced by combining this method with chemotherapy.

Keywords::

• Colon cancer
• radiotherapy
• chemotherapy
• 5-FU
• ²²⁴Ra
• brachytherapy

Acknowledgements

This work was supported in part by The Roberts-Guthman Chair in Immunopharmacology, The German Israeli Fund, The Israel Cancer Association, and Althera Medical Ltd. We thank Dr Gideon Halperin for assistance with the statistical analysis.

Declaration of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.