Antitumor Activity of Novel Bone-seeking, α-emitting 224Ra-solution in a Breast Cancer Skeletal Metastases Model

Abstract

Background/aim: Bone metastases are associated with increased morbidity and poor prognosis in a variety of cancers. The present study investigated the effects of targeted radionuclide therapy with α-emitting, bone-seeking radium-224 (²²⁴Ra) on osteolytic bone metastasis of MDA-MB-231(SA)-GFP human breast cancer cells injected intracardially into nude mice.

Materials and methods: Vehicle, ethylenediamine tetra (methylene phosphonic acid) (EDTMP) and ²²⁴Ra-solution (45, 91 or 179 kBq/kg) with EDTMP were intravenously administered to mice two days after cell injection. The bone-seeking EDTMP was added to the ²²⁴Ra-solution to improve bone targeting of ²¹²Pb, which is a progeny of ²²⁴Ra.

Results: Radium-224 solution treatment decreased in a dose-dependent manner the areas of osteolytic lesions in the hind limbs and the number of tumor foci in the whole skeleton, and extended survival. Paraplegia was not observed in 179 kBq/kg ²²⁴Ra-solution group.

Conclusion: Radium-224-solution containing chelated ²¹²Pb is a promising candidate for the treatment of breast cancer patients with bone metastases.

Keywords: Bone metastasis; breast cancer; radionuclide; radium-224; targeted α-therapy.