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Unlabelled: Glial neoplasms of the human central nervous system have defied treatment, in part because of the limited selectivity of available cytotoxic agents. The thymidine analog 5-iodo-2'-deoxyuridine radiolabeled with the Auger electron emitter 125I (125IUdR) is highly toxic to dividing cells when it is deoxyribonucleic acid incorporated, but it is relatively innocuous when located outside the nucleus. Previous studies have shown that 125IUdR has significant antineoplastic potential against mammalian cells in vitro and direct administration of 125IUdR is effective therapy for ovarian ascites tumors in mice and neoplastic meningitis in rats. Studies using external gamma imaging and autoradiography have also shown that direct intratumoral administration of 123IUdR/125IUdR into intracerebral 9L gliosarcomas in rats results in selective uptake of the radionuclide into tumor cells. Based on these encouraging results, we have evaluated the therapeutic potential of 125IUdR in rats bearing intracerebral 9L gliosarcomas., Methods: Iodine-125-IUdR was infused intracerebrally over a 2-day period into rats bearing 1-day-old 9L tumors and over a 6-day period into animals with 9-day-old 9L tumors; equimolar concentrations of 127IUdR were infused into control animals. Tumor growth was monitored by contrast-enhanced 1H MRI and animal survival was followed over time., Results: Intracerebral tumors (3-7 mm) were readily detected by MRI. Tumor-bearing rats treated with 127IUdR succumbed within 17-24 days, whereas tumor-bearing animals treated with 125IUdR survived significantly longer, and 10%-20% of the animals were cured of tumors., Conclusion: These data substantiate the antineoplastic potential of 5-[125I]iodo-2'-deoxyuridine and indicate that it may be a useful agent for the therapy of solid tumors that are accessible to direct radiopharmaceutical administration.

Unlabelled: Due to their high affinity for biotin, avidin (Av) and streptavidin (SAv) are used to bridge pretargeted antibody molecules and radiolabeled biotin derivatives in vivo., Methods: We compared uptake of 125I-labeled Av or SAv (approximately 10-500 micrograms) in tumor and normal tissues 3 days after a biotinylated B72.3 monoclonal antibody (100 micrograms) injection in nude mice. The animals were killed 24 hr later and the biodistribution of 125I was determined., Results: The percent injected dose per gram of tumor remained constant over the range of injected doses for Av while that for SAv varied. As larger amounts of Av/SAv were injected, the number of moles of each trapped within tumor increased, with the values for SAv being much higher. While the injection of larger doses of Av led to an increase in tumor-to-normal tissue ratios, that of SAv did not., Conclusion: SAv (2.5 mg/kg) is the preferred "second-step" reagent. At this dose, the number of receptors available for targeting by radiolabeled biotin derivatives is approximately 1.8 times the number of antigen-binding sites accessible for targeting by radiolabeled antibody. Additional targeted-signal amplification should be possible by the successive and repeated administration of such polymeric reagents, each exhibiting high affinity to and forming a specific binding pair with the last-targeted molecule.