Asta Juzeniene1, Jenni Bernoulli2, Mari Suominen2, Jussi Halleen2, Roy Hartvig Larsen3. 1. Department of Radiation Biology, Institute for Cancer Research, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway. 2. Pharmatest Services Ltd, Turku, Finland. 3. Sciencons AS, Oslo, Norway royhlars1@gmail.com.
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. Copyright
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 humanbreast 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 cancerpatients with bone metastases. Copyright
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