Kassis A I, Wen P Y, Van den Abbeele A D, Baranowska-Kortylewicz J, Makrigiorgos G M, Metz K R, Matalka K Z, Cook C U, Sahu S K, Black P M, Adelstein S J
Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
J Nucl Med. 1998 Jul;39(7):1148-54.
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.
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.
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.
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.
人类中枢神经系统的神经胶质瘤难以治疗，部分原因是现有细胞毒性药物的选择性有限。用俄歇电子发射体125I标记的胸苷类似物5-碘-2'-脱氧尿苷（125IUdR）在掺入脱氧核糖核酸时对分裂细胞具有高度毒性，但位于细胞核外时相对无害。先前的研究表明，125IUdR在体外对哺乳动物细胞具有显著的抗肿瘤潜力，直接给予125IUdR对小鼠卵巢腹水肿瘤和大鼠肿瘤性脑膜炎是有效的治疗方法。使用外部γ成像和放射自显影的研究还表明，将123IUdR/125IUdR直接瘤内注射到大鼠脑内9L胶质肉瘤中会导致放射性核素选择性摄取到肿瘤细胞中。基于这些令人鼓舞的结果，我们评估了125IUdR对携带脑内9L胶质肉瘤的大鼠的治疗潜力。
将碘-125-IUdR在2天内脑内注入携带1日龄9L肿瘤的大鼠，并在6天内注入携带9日龄9L肿瘤的动物；将等摩尔浓度的127IUdR注入对照动物。通过对比增强1H MRI监测肿瘤生长，并随时间跟踪动物存活情况。
MRI很容易检测到脑内肿瘤（3-7毫米）。用127IUdR治疗的荷瘤大鼠在17-24天内死亡，而用125IUdR治疗的荷瘤动物存活时间明显更长，10%-20%的动物肿瘤治愈。
这些数据证实了5-[I25I]碘-2'-脱氧尿苷的抗肿瘤潜力，并表明它可能是一种对可直接给予放射性药物的实体瘤治疗有用的药物。
