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Influence of dose and schedule on the therapeutic efficacy of 131I-labelled monoclonal antibody 139H2 in a human ovarian cancer xenograft model.

Abstract
The therapeutic efficacy of various doses and schedules of 131I-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 mm3). The anti-tumor effects induced by i.v. injections of 131I-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 muCi 131I-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 muCi 131I-MAb 139H2 per mouse, given as 10 injections of 100 muCi (3 x/week), 4 injections of 250 muCi (2 x/week), 10 injections of 100 muCi (5 x/week) within a period of 3 weeks, or 2 injections of 500 muCi with a 2-week interval, was 9%, 40%, 64% and 75% respectively. Unlabelled MAb 139H2 did not affect tumor growth, while the effects of 131I-control MAb were minor and transient. 131I-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 muCi 131I-MAb 139H2) given with the 2-week interval. The radiation dose to the tumor after a single injection of 500 muCi 131I-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.
AuthorsC F Molthoff, H M Pinedo, H M Schlüper, E Boven
JournalInternational journal of cancer (Int J Cancer) Vol. 50 Issue 3 Pg. 474-80 (Feb 01 1992) ISSN: 0020-7136 [Print] United States
PMID1735615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antibodies, Monoclonal
  • Immunotoxins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Mucin-1
Topics
  • Animals
  • Antibodies, Monoclonal (administration & dosage, metabolism)
  • Autoradiography
  • Dose-Response Relationship, Radiation
  • Female
  • Humans
  • Immunotherapy
  • Immunotoxins (administration & dosage)
  • Iodine Radioisotopes (therapeutic use)
  • Membrane Glycoproteins (immunology)
  • Mice
  • Mucin-1
  • Neoplasm Transplantation
  • Ovarian Neoplasms (pathology, therapy)

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