TY - JOUR
T1 - 5-[123I]iodo-2′-deoxyuridine in the radiotherapy of an early ascites tumor model
AU - Baranowska-Kortylewicz, Janina
AU - Makrigiorgos, G. Mike
AU - Van Den Abbeele, Annick D.
AU - Berman, Robert M.
AU - Adelstein, S. James
AU - Kassis, Amin I.
N1 - Funding Information:
This work was supported by NIH Grant ROl CA 15523-15. Presented in part at the Society of Nuclear Medicine 36* Annual Meeting, St. Louis, MO, 13-16, June 1989. Reprints requests to: Amin I. Kassis, Ph.D., Harvard Medical
PY - 1991/11
Y1 - 1991/11
N2 - 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 (ig.) murine ovarian tumor (MOT) in female C3HeB/Fej mice. Total doses of 0.37 to 8.88 MBq (10-240 μCi) 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 × 106 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 × 106 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 μCi) 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.
AB - 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 (ig.) murine ovarian tumor (MOT) in female C3HeB/Fej mice. Total doses of 0.37 to 8.88 MBq (10-240 μCi) 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 × 106 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 × 106 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 μCi) 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.
KW - 5-Iodo-2′-deoxyuridine
KW - Auger-electron emitters
KW - Biodistribution
KW - Dosimetry
KW - Iodine radioisotopes
KW - Murine ovarian tumor
KW - Radiotherapy
KW - Scintigraphy
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U2 - 10.1016/0360-3016(91)90331-W
DO - 10.1016/0360-3016(91)90331-W
M3 - Article
C2 - 1938564
AN - SCOPUS:0025919743
SN - 0360-3016
VL - 21
SP - 1541
EP - 1551
JO - International Journal of Radiation Oncology, Biology, Physics
JF - International Journal of Radiation Oncology, Biology, Physics
IS - 6
ER -