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

Abstract

Introduction: 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 (175Yb-BLM) has been reported. Methods: Yb-175 chloride was obtained by thermal neutron irradiation (3 × 1013 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 60ºC 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 175Yb-BLM were performed in wild-type mice up to 8 days. Results: 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 175Yb-BLM the target tissues were lung, liver and spleen.

Conclusion: 175Yb-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.