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Comparison of 131 I‐labelled anti‐episialin 139H2 with cisplatin, cyclophosphamide or external‐beam radiation for anti‐tumor efficacy in human ovarian cancer xenografts
Author(s) -
Molthoff Carla F. M.,
Pinedo Herbert M.,
Schlüper Hennie M. M.,
Rutgers Derk H.,
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.2910510120
Subject(s) - radioimmunotherapy , monoclonal antibody , medicine , ovarian cancer , cisplatin , cyclophosphamide , biodistribution , radiation therapy , chemotherapy , in vivo , cancer , cancer research , antibody , nuclear medicine , immunology , biology , microbiology and biotechnology
Three human ovarian cancer xenografts of different origin and grown s.c. in nude mice as well‐established tumors were studied for their sensitivity to cisplatin (CDDP), cyclophosphamide (CTX), 131 I‐labelled anti‐episialin monoclonal antibody (MAb) 139H2, or external‐beam radiotherapy. The maximum tolerated dose of CDDP given weekly i.v. × 2 induced a tumor growth inhibition (GI) of 77.5% and 85.1% of the serous xenografts Ov.Ri(C) and OVCAR‐3, respectively. The mucinous xenograft Ov.Pe was relatively resistant to CDDP. The maximum tolerated dose of CTX, given i.p. × 2 with a 2‐week interval, induced a GI between 52.9% and 59.7% for each of the 3 xenografts. Radioimmunotherapy with 500–750 μCi 131 I‐specific MAb 139H2, administered i.v. × 2 with a 2‐week interval, was more effective than CDDP or CTX. The 500 μCi 131 I‐MAb 139H2 schedule induced 100% GI in Ov.Ri(C) xenografts and all tumors were cured. The same schedule was slightly less effective in OVCAR‐3 xenografts, but complete tumor regressions could still be obtained. Ov.Pe xenografts were least sensitive to radioimmunotherapy. The 2 injections of 500 μ‐Ci 131 I‐control MAb gave only transient growth inhibition of OVCAR‐3 and Ov.Pe tumors, but gave complete regressions of Ov.Ri(C) xenografts. Biodistribution using tracer doses of 131 I‐MAb 139H2 and 125 I‐control MAb showed different degrees of specificity for MAb 139H2 in the 3 xenografts. Radiation doses absorbed in Ov.Ri(C), OVCAR‐3 and Ov.Pe xenografts per 10 μCi injected dose were 30, 41 and 29 cGy respectively. Treatment with 10 Gy external‐beam radiation suggested that the effects of radioimmunotherapy in each tumor line were related to the intrinsic radiosensitivity of the xenografts.