The administration of radiolabeled monoclonal antibodies to improve the treatment of malignant gliomas is dependent upon achieving effective tumor radiation dose while sparing normal tissues. We have evaluated the efficacy of 131I-labeled F(ab′)2 fragment of monoclonal antibody Mel-14, an IgG2a reactive with the chondroitin sulfate proteoglycan antigen of gliomas, melanomas, and other neoplasms, in prolonging survival of athymic mice transplanted intracerebrally with D-54 MG human glioma xenografts. Studies indicated that in vitro immunoreactivity, affinity, and tumor localization in vivo of radiolabeled Mel-14 F(ab′)2 were maintained at specific activities of 10–13 µCi/µg. Intravenous injection of 1500 µCi/115 µg or 2000 µCi/154 µg 131I-labeled Mel-14 F(ab′)2 into mice 6–7 days after xenograft implantation resulted in significant survival prolongation over control animals (P = 0.009 using Wilcoxon rank sum analysis). In another experiment, 1500 µCi/126 µg 131I-labeled Mel-14 F(ab′)2 improved survival significantly over controls (P = 0.006), while 1500 µCi/220 µg 131I-labeled nonspecific antibody did not (P = 0.2). Increasing the injected radiation dose to 3000 µCi 131I-labeled Mel-14 F(ab′)2 did not significantly increase survival in tumor-bearing mice, because of supervening radiation toxicity. However, giving 3000 µCi 131I-labeled Mel-14 F(ab′)2 in two doses of 1500 µCi, 48 h apart, did significantly prolong animal survival over controls (P = 0.001). Estimated radiation dose to tumor was 915 rad after injection of 3000 µCi 131I-labeled Mel-14 F(ab′)2 in two doses, a dose higher than that delivered to normal tissues. The results of this study suggest that radiolabeled Mel-14 F(ab′)2 be evaluated as an agent for radioimmunotherapy trials.


Supported by NIH Grants CA 11898, CA 42324, CA 44640, NS 20023, and NS 00958, and American Cancer Society Grant CH 403.

This content is only available via PDF.