Comparison of 131I-labelled anti-episialin 139H2 with cisplatin, cyclophosphamide or external-beam radiation for anti-tumor efficacy in human ovarian cancer xenografts

C. F M Molthoff, H. M. Pinedo, H. M M Schluper, D. H. Rutgers, E. Boven

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Abstract

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), 131I-labelled anti-episialin monoclonal antibody (MAb) 139H2, or external-beam radiotherapy. The maximum tolerated dose of CDDP given weekly i.v. x 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. x 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 131I specific MAb 139H2, administered i.v. x 2 with a 2-week interval, was more effective than CDDP or CTX. The 500 μCi 131I-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 μCi 131I-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 131I-MAb 139H2 and 125I-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.

Original languageEnglish (US)
Pages (from-to)108-115
Number of pages8
JournalInternational Journal of Cancer
Volume51
Issue number1
DOIs
Publication statusPublished - 1992
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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