Pharmacokinetics and biodistribution of a new anti-episialin monoclonal antibody 139H2 in ovarian-cancer-bearing nude mice.
The new murine anti-episialin monoclonal antibody (mAb) 139H2 has been selected for its strong reactivity with a series of human ovarian cancer xenografts. In the present report we describe the characteristics of mAb 139H2 investigated in vitro as well as in vivo. Scatchard plot analysis using the human ovarian cancer cell line NIH:OVCAR-3 showed an affinity constant of 1 x 10(8) M-1 and the expression of 7 x 10(6) antigenic sites/cell. Reactivity with OVCAR-3 xenograft tissue was intense, localized at the cell membrane, heterogeneously distributed, and mainly detectable at the apical site of the cell. Administration of radiolabelled mAb 139H2 to nude mice bearing s.c. OVCAR-3 xenografts showed specific uptake in the tumour up to 9% of the injected dose/g. The maximum uptake in the tumour was retained for 3.5 days and mAb 139H2 cleared from the tumour with a half-life of 5.5 days. The half-life in blood was 50 h and no antibody-antigen complex formation could be detected. Poor uptake and no retention in episialin-negative WiDr colon cancer xenografts demonstrated specificity. Administration of an excess of an unlabelled irrelevant mAb did not influence the uptake in the OVCAR-3 xenografts or in other tissues. In contrast, tumour uptake decreased after addition of 300 micrograms or more unlabelled mAb 139H2 to a tracer dose of radiolabelled mAb 139H2. The uptake of mAb 139H2 in OVCAR-3 xenografts appeared inversely related to the tumour size.
Molthoff
C F
CF
Free University Hospital, Department of Oncology, Amsterdam, The Netherlands.
Pinedo
H M
HM
Schlüper
H M
HM
Boven
E
E
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D005260:Female; D006801:Humans; D000922:Immunotoxins / Q000378:metabolism; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D018396:Mucin-1; D010051:Ovarian Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism*; D010599:Pharmacokinetics; D016719:Radioimmunodetection; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D000922:Immunotoxins; D007457:Iodine Radioisotopes; D008562:Membrane Glycoproteins; D018396:Mucin-1