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5-[¹²⁵I]Iodo-2'-Deoxyuridine in the Radiotherapy of Brain Tumors in Rats

Departments of Radiology, Neurology and Neurosurgery, Harvard Medical School, Boston, Massachusetts

Correspondence: For correspondence or reprints contact: Amin I. Kassis, PhD, Department of Radiol ogy, Harvard Medicol School, Goldenson Building, 220 Longwood Ave., Boston, MA 02115.

ABSTRACT

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 ¹²⁵IUdR/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-lUdR 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 ¹²⁵IUdR were infused into control animals. Tumor growth was monitored by contrast-enhanced ¹H MRI and animal survival was followed overtime. 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 anlineoplastic 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.

Key Words: 5-iodo-2'-deoxyuridine • Auger electrons • iodine-125 • brain tumor therapy • locoregional administration

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