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.