Radiosynthesis and evaluation of ytterbium-175 labeled bleomycin as therepeutic agent

ABSTRACT

Bleomycins are DNA-binding biomolecules, which can be used as targeted therapy carriers when labeled with particle-emitters such as Yb-175. In this work the development of Yb-175 bleomycin [[175]Yb-BLM] has been reported. Yb-175 chloride was obtained by thermal neutron irradiation [3 × 10[13] n.cm[-2].s[-1]] of natural Yb2O3 samples at various neutron fluxes and irradiation times. The radionuclide dissolved in acidic media [120mCi/mg] was used in the bleomycin [5 mg] labeling in buffer solution and warming at 60[degree sign]C for 48 h. Radiochemical purity was determined by ITLC as well as specific activity calculation followed by stability studies. Biodistribution studies of free Yb-175 and [175]Yb-BLM were performed in wild-type mice up to 8 days. At optimized conditions radiochemical purity of 97 +/- 0.88% and specific activity of 1360 MBq/mM was obtained. Biodistribution studies of free Yb-175 demonstrated liver and bone uptake while in case of [175]Yb-BLM the target tissues were lung, liver and spleen.[175]Yb-BLM complex was prepared at the optimized conditions and suitable characteristics. The accumulation of the radiolabeled compound in lungs, liver and spleen demonstrates a similar pattern to the other radiolabeled bleomycins. Further studies are to be performed for application of this labeled compound in tumor-bearing models