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• W2199435751 abstract "Radiolabeled bisphosphonates (BPs) have been used for bone imaging and delivery of β− emitting radionuclides for bone pain palliation. As a β− emitter, 188Re has been considered particularly promising for bone metastases therapy. Aimed at finding innovative bone-seeking agents for systemic radiotherapy of bone metastases, we describe herein novel organometallic compounds of the type fac-[188Re(CO)3(k3-L)], (L = BP-containing chelator), their in vitro and in vivo stability, and their cellular damage in MDAMB231 cells, a metastatic breast cancer cell line. After synthesis and characterization of the novel organometallic compounds of the type fac-[188Re(CO)3(k3-L)] their radiochemical purity and in vitro stability was assessed by HPLC. In vivo stability and pharmacokinetic profile were evaluated in mice and the radiocytotoxic activity and DNA damage were assessed by MTT assay and by the cytokinesis-block micronucleus (CBMN) assay, respectively. Among all complexes, 188Re3 was obtained with high radiochemical purity (> 95%) and high specific activity and presented high in vitro and in vivo stability. Biodistribution studies of 188Re3 in Balb/c mice showed fast blood clearance, high bone uptake (16.1 ± 3.3% IA/g organ, 1 h p.i.) and high bone-to-blood and bone-to-muscle radioactivity ratios, indicating that it is able to deliver radiation to bone in a very selective way. The radiocytotoxic effect elicited by 188Re3 in the MDAMB231 cells was dependent on its concentration, and was higher than that induced by identical concentrations of [188ReO4]−. Additionally, 188Re3 elicited morphological changes in the cells and induced DNA damage by the increased number of MN observed. Altogether, our results demonstrate that 188Re3 could be considered an attractive candidate for further preclinical evaluation for systemic radionuclide therapy of bone metastases considering its ability to deliver radiation to bone in a very selective way and to induce radiation damage." @default.
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• W2199435751 date "2016-02-01" @default.
• W2199435751 modified "2023-09-25" @default.
• W2199435751 title "Novel 188 Re multi-functional bone-seeking compounds: Synthesis, biological and radiotoxic effects in metastatic breast cancer cells" @default.
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• W2199435751 doi "https://doi.org/10.1016/j.nucmedbio.2015.11.004" @default.
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