5-[123I]iodo-2'-deoxyuridine in the radiotherapy of an early ascites tumor model.
The extreme biological toxicity of Auger emitters is caused by the decay-associated, highly localized deposition of energy. The antineoplastic capability of an Auger-electron emitter, iodine-123, incorporated into the thymidine analog, 5-iodo-2'-deoxyuridine (IUdR) was evaluated in an intraperitoneal (i.p.) murine ovarian tumor (MOT) in female C3HeB/FeJ mice. Total doses of 0.37 to 8.88 MBq (10-240 microCi) 123IUdR were administered i.p. in five equally divided fractions at 24, 28, 32, 36, and 40 hr after the i.p. inoculation of 0.5 to 1.6 x 10(6) tumor cells per mouse. Control tumor-bearing animals were injected with identical volumes of saline at 4-hr intervals. Biodistribution studies demonstrated a distinct and localized uptake of 123IUdR in the MOT cells (1% of the injected dose was associated with MOT cells 24 hr after the last injection), whereas in animals without tumor there was no radioactivity associated with the peritoneal cells. Analogous results were obtained from scintigraphic images where the focal area of abdominal activity persisted only in MOT-bearing mice while it cleared from the abdomen of the controls. The 50% survival (median survival) of the control group was 19 days for an inoculum of 1.6 x 10(6) MOT cells per animal, whereas the median survival of MOT-bearing animals treated with 123IUdR increased by 11 days for the highest administered dose (8.88 MBq, 240 microCi) and resulted in a 20% absolute survival at 7 weeks. Statistically significant absolute survival prolongation was found with all of the total administered doses. The prolongation of both median and absolute survival time of the tumor-bearing animals treated with 123IUdR conclusively indicates the substantial antineoplastic activity of the Auger-electron emitter iodine-123.
Department of Radiology (Nuclear Medicine), Shields Warren Radiation Laboratory, Harvard Medical School, Boston, MA 02115.
J
J
Baranowska-Kortylewicz
G M
GM
Makrigiorgos
A D
AD
Van den Abbeele
R M
RM
Berman
S J
SJ
Adelstein
A I
AI
Kassis
D000818:Animals; D001201:Ascites / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D002453:Cell Cycle; D004354:Drug Screening Assays, Antitumor; D005260:Female; D007065:Idoxuridine / Q000493:pharmacokinetics / Q000627:therapeutic use*; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D016019:Survival Analysis; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D007065:Idoxuridine