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

作者：Juzeniene Asta; Bernoulli Jenni; Suominen Mari; Halleen Jussi; Larsen Roy Hartvig^*

来源：Anticancer Research, 2018, 38(4): 1947-1955.

DOI：10.21873/anticanres.12432

• Bone metastasis
• breast cancer
• radionuclide
• radium-224
• targeted alpha-therapy

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 alpha-emitting, bone-seeking radium-224 (Ra-224) 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 Ra-224-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 Ra-224-solution to improve bone targeting of Pb-212, which is a progeny of Ra-224. 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 Ra-224-solution group. Conclusion: Radium-224-solution containing chelated Pb-212 is a promising candidate for the treatment of breast cancer patients with bone metastases.

• 出版日期2018-4