[Effect of 131I-labeled recombinant human tumor necrosis factor-alpha on the nude mice bearing human hepatoma].
OBJECTIVE
To test the effect of recombinant human tumor necrosis factor-alpha (rhTNF-alpha) labeled with 131I on tumor growth in the nude mice bearing human hepatoma.


METHODS
The biological activity of 131I-rhTNF-alpha was tested through in vitro combination of the radioactive drug and SMMC-7721 cells. The BALB/c-nu/ nu mice model bearing human hepatoma were established by injecting single cell suspension of SMMC-7721 cells. When the tumor was 1 cm in diameter, the therapeutic experiment was carried out. Twenty-four nude mice bearing human hepatoma were divided into six groups according the area of tumor, weight and sex of the nude mice. After i. v administration of 131I-rhTNF-alpha, the body biodistribution of 131I-rhTNF-alpha was assessed during a short-term (30 min, 1 h, 6 h) and a long-term (12 h, 24 h, 48 h) period. The biological activity and tumor accumulation of 131I-rhTNF-alpha were investigated. In the end of the experiment, histopathologic examinations of tumor samples were undertaken.


RESULTS
The combination of 131I-rhTNF-alpha with the human hepatoma SMMC-7721 cells existed dose dependence and saturability. The 131I-rhTNF-alpha had satisfactory immunoreactivity. The 131I-rhTNF-alpha accumulated in tumor tissues well and kept stable for several days. The tumor tissues accumulated the highest radioactivity at 6 h, and still maintained 67.5% of that radioactivity at 48 h. The 131I-rhTNF-alpha administrated either intravenously or intratumorally could inhibit tumor growth. The 131I-rhTNF-alpha had similar radioactivity as the positive control (P>0.05), but greater radioactivity than the control groups including 131I, rhTNF-alpha and the negative groups (P<0.05).


CONCLUSIONS
The radioactive compound of 131I-rhTNF-alpha can inhibit and kill tumor cells, which demonstrates its potential for treating hepatocarcinoma.
Long
Ya-Hong
YH
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.
Li
Yun-Chun
YC
Mi
Yan-Xia
YX
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000532:radiotherapy; D006801:Humans; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011994:Recombinant Proteins / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha