Treatment of hepatocellular carcinoma with 188Re-Hepama-1 monoclonal antibody in nude mice

Objective: The tissue distribution and tumor suppression of 188Re labeled monoclonal antibody Hepama-1 were studied in nude mice models with hepatocellular carcinoma (HCC). Methods: HCC line SMMC-7721 was transplanted into 40 nude mice equally divided into 5 groups: intratumoral 188ReO4- (GB), intratumoral 188Re-mIgG(GC), intravenous 188Re-Hepama-1 (GD) and intratumoral 188Re- Hepama-1 (GE) treatment, and a control group (GA) with saline. After 48 h, 3 mice from each group were sacrificed to assess the biodistribution. At the 1 st, 2nd, 3rd and 4th week after treatment, the tumor volume in each group was measured. Three mice from each group were sacrificed after the 4th week measurement to investigate the micro structural and pathological changes. Results: The labeling rate of 188Re-Hepama-1 was 85%, and the radiochemical purity was more than 95%. The tumor uptakes (percentage activity of injection dose per gram of tissue, % ID/g) of 188Re-Heparna-1 in GE and GD at 48 h after intratumoral or intravenous administration were 11.53 % ID/g and 2.79 % ID/g, respectively, which were significantly higher than other groups (P<0.05). The tumor volume in GE and GD was smaller than in other groups. The morphological changes of nuclear chromatin, apoptotic bodies and cell necrosis were significantly more obvious in the two 188Re-Hepama-1 treated groups. Conclusions: 188Re-Hepama-1 treatment is effective in nude mice model of HCC. It might have potential role on the targeting treatment of human HCC. (authors)