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Yttrium-90 and Iodine-131 Radioimmunoglobulin Therapy of an Experimental Human Hepatoma¹

The Johns Hopkins Oncology Center, Department of Radiation Oncology, Baltimore, Maryland 21205 [J. L. K., K. A. K., J. R. W., L. E. D., S. E. O., P. K. L.]; Institut Jules Bordet, Service de Radiotherapie, Bruxelles, Belgium [T. H. N.]; The Johns Hopkins School of Medicine, Department of Comparative Medicine, Baltimore, Maryland 21205 [P. L.]; George Washington University, Division of Radiation Oncology, Washington, DC [B. W. W.]; and Hybritech, Inc., San Diego, California [J. F.]

Therapeutic trials were performed on the HepG2 human hepatoblastoma implanted s.c. in the athymic nude mouse. Animals were treated with polyclonal and monoclonal antiferritin and control antibodies labeled with either iodine-131 (¹³¹I) or yttrium-90 (⁹⁰Y). Administration of 400 µCi of ¹³¹I-labeled polyclonal antiferritin or 300 µCi of ⁹⁰Y-labeled polyclonal antiferritin significantly increased survival (P < 0.001). There were no tumor cures with radiolabeled polyclonal antibody therapy. Animals treated with 200 or 300 µCi of ¹³¹I-labeled monoclonal antiferritin (QCI054) did not show increased survival compared to controls. Although 400 µCi of ¹³¹I-labeled QCI significantly prolonged survival, treatment resulted in no long-term survivors. Monoclonal antiferritin labeled with ⁹⁰Y significantly prolonged survival of animals (P < 0.001) at doses of 100, 200, or 300 µCi compared with untreated controls. Fifty % of the animals treated with 200 µCi and 75% of the animals treated with 300 µCi showed no evidence of disease at 140 days following treatment. Four hundred µCi of ⁹⁰Y-labeled QCI proved toxic to the animals. Increased survival was accompanied by a decrease in tumor mitotic rate and an increase in cellular polymorphism as determined by pathological examination. The radiation dose absorbed in the tumor correlated directly with tumor response following treatment. The absorbed dose in tumors for complete decay of the isotope ranged from 165 and 330 cGy at the periphery and center of small tumors for an administered activity of 200 µCi of ¹³¹I-labeled polyclonal antiferritin, to 7,573 and 12,400 cGy for 300 µCi of ⁹⁰Y-labeled monoclonal antiferritin QCI.

¹ Supported by NIH Grants CA-43791, CA-06973, and RR-00130; DOE grant DE-FG02-89ER6087; a fellowship grant from Merck Sharpe and Dohme (P. L.); and by Hybritech, Inc.

² To whom requests for reprints should be addressed, at The Johns Hopkins Oncology Center, 600 North Wolfe Street, Room 2-109, Baltimore, MD 21205.

Received 6/13/89. Revised 8/16/89. Accepted 8/21/89.

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