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Influence of dose and schedule on the therapeutic efficacy of 131 I‐labelled monoclonal antibody 139H2 in a human ovarian cancer xenograft model
Author(s) -
Molthoff Carla P. M.,
Pinedo Herbert M.,
Schlüper Hennie M. M.,
Boven Epie
Publication year - 1992
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910500324
Subject(s) - radioimmunotherapy , monoclonal antibody , medicine , ovarian cancer , radiation therapy , antibody , cancer , nuclear medicine , urology , immunology
The therapeutic efficacy of various doses and schedules of 131 I‐labelled anti‐episialin monoclonal antibody (MAb) 139H2 was assessed in the NIH:OVCAR‐3 human ovarian cancer xenograft model. Radioimmunotherapy was started at the time s.c. tumors were well established (100 to 300 mm 3 ). The anti‐tumor effects induced by i.v. injections of 131 I‐MAb 139H2 were dose‐ and schedule‐dependent. Optimal growth inhibition and long‐lasting complete tumor regressions were obtained with 2 injections of 500, 700 or 750 μCi 131 I‐MAb 139H2 per mouse given with a 2‐week interval. The percentage of tumors with more than 50% reduction of their initial volume after treatment with a total dose of 1,000 μCi 131 I‐MAb 139H2 per mouse, given as 10 injections of 100 μCi (3 ± /week), 4 injections of 250 μCi (2 × /week), 10 injections of 100 μCi (5 ×/week) within a period of 3 weeks, or 2 injections of 500 μCi with a 2‐week interval, was 9%, 40%, 64% and 75% respectively. Unlabelled MAb 139H2 did not affect tumor growth, while the effects of 131 I‐control MAb were minor and transient. 131 I‐MAb 139H2 treatment did not select for outgrowth of episialin‐ negative cells in the OVCAR‐3 xenografts. Highest absorbed doses of whole‐body‐radiation were calculated for 2 injections (500 to 750 μCi 131 I‐MAb 139H2) given with the 2‐week interval. The radiation dose to, the tumor after a single injection of 500 μCi 131 I‐MAb 139H2 was 1,300 cGy over 7 days, which appeared slightly lower than the dose calculated after administration of a tracer dose of iodinated MAb 139H2.