Biological studies of samarium-153 bleomycin complex in human breast cancer murine xenografts for therapeutic applications

Abstract

In this work, a potential therapeutic DNA targeting agent, 153 Sm-bleomycin complex ( 153 Sm-BLM), was developed and the tumor accumulation studies were performed using single photon emission computed tomography (SPECT) and scarification studies. 153 Sm-BLM was prepared at optimized conditions (room temperature, 4-8 h, 0.1 mg bleomycin for 740-3700 MBq 153 SmCl 3 , radiochemical purity over 98%, HPLC, specific activity = 55 TBq/mmol). 153 Sm-BLM was administered into human breast cancer murine xenografts and the biodistribution and imaging studies were performed up to 48 h. 153 Sm-BLM demonstrated superior tumor accumulation properties in contrast with the other radiolabeled bleomycins with tumor: blood ratios of 41, 72 and 182 at 4, 24 and 48 h, respectively, and tumor: muscle ratios of 23, 33 and > 1490 at 4, 24 and 48 h, respectively, while administered intravenously. The SPECT images also demonstrated the obvious tumor uptake at the chest region of the breast-tumor bearing mice. These initial experiments demonstrate significant accumulation of 153 Sm-BLM in tumor tissues.