Immunoscintigraphy of xenotransplanted hepatoblastoma with iodine 131-labeled anti-alpha-fetoprotein monoclonal antibody.

BACKGROUND/PURPOSE: Hepatoblastoma (HB) is the most common primary malignant liver tumor affecting infants and young children. The alpha-fetoprotein level is elevated in 95% of all children with hepatoblastoma. Therefore, it is of interest to assess targeting of the HB marker alpha-fetoprotein by antibody imaging. In this pilot study, the authors investigated the radioimmunoscintigraphy of xenotransplanted HB in nude mice utilizing an anti-alpha-fetoprotein antibody. METHODS: HB cell suspensions from tumors of 3 children were transplanted subcutaneously into nude mice NMRI (nu/nu). A total of 200 microg of intact anti-alpha-fetoprotein antibody was injected intravenously into 8 animals from each HB. Before injection, the monoclonal antibody was labeled with iodine (I) 131 (specific activity of 75 MBq/mg, labeling yield of 95%) using the conventional iodogen method. Planar scintigraphic images of anesthetized mice in posterior views were acquired with a gamma camera immediately after injection, and after 1, 2, 3, 7, and 14 days. The biodistribution data were obtained by killing and dissecting animals, and the activity in the tissues was measured in a gamma counter. The alpha-fetoprotein levels in the animals' sera were recorded 15 days after imaging and were compared with the control group. RESULTS: A total of 66% of the hepatoblastomas could be detected by scintigraphy. Within 24 hours, the mean specific tumor uptake in nude mice hepatoblastomas with a volume of over 1,000 mm3, was 14% per injected dose (+/-3.9%). The biological half-life of the labeled antibody complex in the tumor was 3.86 (+/-0.84) days. Thyroid uptake of free I-131 was 2.85% per injected dose (+/-1.5%) reflecting the deiodination of the labeled antibody complex. CONCLUSIONS: The results show the possibility of imaging xenotransplanted hepatoblastoma with 131I-labeled anti-alpha-fetoprotein and may, in the future, determine tumor recurrence and extension, and thereby improve the prognosis of advanced HBs.

Paclitaxel: an effective antineoplastic agent in the treatment of xenotransplanted hepatoblastoma.

BACKGROUND: Hepatoblastoma is an uncommon liver tumor of infancy and early childhood. Though most patients with nonmetastatic hepatoblastomas can be cured by defining surgical strategies and chemotherapy regimes, new drugs are needed for children with advanced hepatoblastomas. The activity of paclitaxel as a new antineoplastic agent with limited experience in pediatric oncology was studied in a xenograft model. PROCEDURE: Hepatoblastoma cell suspensions from three children were transplanted subcutaneously into nude mice NMRI (nu/nu). One of the primary tumors was an embryonal multifocal hepatoblastoma, whereas the other tumors were embryonal/fetal hepatoblastomas localized on a liver lobe. After 4 weeks, xenografted tumor sizes reached 50-100 mm3. The xenografted tumors resembled their originals histologically and produced high levels of alpha-fetoprotein. The efficiency of paclitaxel at equitoxic doses was analyzed. RESULTS: Paclitaxel produced an effect in all three hepatoblastomas. There was a significant reduction of tumor volume (P < 0.001) and alpha-fetoprotein levels after chemotherapy (P < 0.0001). The proliferation activity of the tumor cells corresponded with these results. Histologically, after treatment with paclitaxel the tumor regression was 35%-49%. The mechanism of paclitaxel action could be demonstrated by light microscopy immunohistochemistry and electron microscopy. CONCLUSIONS: The preliminary results in phase I trials of solid tumors in children and the results of this study suggest that paclitaxel in phase II studies can now be entertained for patients with hepatoblastoma.