5-[125I]iodo-2'-deoxyuridine in the radiotherapy of brain tumors in rats.
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.


CONCLUSIONS
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.
Kassis
A I
AI
Department of Radiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Wen
P Y
PY
Van den Abbeele
A D
AD
Baranowska-Kortylewicz
J
J
Makrigiorgos
G M
GM
Metz
K R
KR
Matalka
K Z
KZ
Cook
C U
CU
Sahu
S K
SK
Black
P M
PM
Adelstein
S J
SJ
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use; D001921:Brain / Q000473:pathology; D001932:Brain Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D004247:DNA / Q000096:biosynthesis*; D018316:Gliosarcoma / Q000473:pathology / Q000532:radiotherapy*; D007065:Idoxuridine / Q000008:administration & dosage / Q000627:therapeutic use*; D015552:Injections, Intralesional; D007457:Iodine Radioisotopes / Q000008:administration & dosage / Q000627:therapeutic use*; D008279:Magnetic Resonance Imaging; D009368:Neoplasm Transplantation; D019384:Nucleic Acid Synthesis Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D019275:Radiopharmaceuticals / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013238:Stereotaxic Techniques; D013997:Time Factors
D000970:Antineoplastic Agents; D007457:Iodine Radioisotopes; D019384:Nucleic Acid Synthesis Inhibitors; D019275:Radiopharmaceuticals; D004247:DNA; D007065:Idoxuridine