Localization of radiolabelled F(ab')2 fragments of monoclonal antibodies in nude mice bearing intraperitoneally growing human ovarian cancer xenografts.
The biodistribution and pharmacokinetics of 2 monoclonal antibodies (MAbs) specific for ovarian carcinoma, OC125 and OV-TL3, were studied in nude mice bearing intraperitoneally (i.p.) growing human ovarian carcinoma xenografts of NIH:OVCAR-3. The ovarian carcinoma xenografts grew as non-adherent cells in ascites and as solid implants in the peritoneal cavity of injected mice. The biodistribution and pharmacokinetics were determined by measurement of radioactivity in tumor masses, ascites, blood and other tissues after intravenous (i.v.) and i.p. injection of radioiodinated F(ab')2 fragments of MAbs. The specificity of the observed tumor localization was then evaluated by comparing the uptake of the anti-ovarian carcinoma antibodies OC125 and OV-TL3 with the uptake of a radioiodinated non-ovarian carcinoma-specific MAb A2C6. The results of the study indicate that uptake of the anti-ovarian carcinoma antibodies was highest in the non-adherent tumor cells in the ascites after i.p. injection. The observed uptake was 85% injected dose/g for OV-TL3 and 22% injected dose/g for OC125. This compares to the observed antibody uptake of 9% injected dose/g for OV-TL3 and less than 1% injected dose/g for OC125 in solid tumor masses after i.p. injection. After i.v. injection, uptake of OC125 and OV-TL3 was less than 3% injected dose/g, both for nonadherent tumor cells and for solid tumor masses. The data support the conclusion that OV-TL3 is superior to OC125 and that i.p. administration of radiolabelled MAb F(ab')2 fragments is superior to their i.v. administration for immunotherapy of ovarian carcinoma.
Division of Gynecologic Oncology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115.
K R
KR
Moseley
A
A
Battaile
R C
RC
Knapp
H J
HJ
Haisma
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis* / Q000627:therapeutic use; D001345:Autoradiography; D005260:Female; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000032:analysis*; D007150:Immunohistochemistry; D008657:Metabolic Clearance Rate; D051379:Mice; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology*; D014018:Tissue Distribution; D014183:Transplantation, Heterologous
D000911:Antibodies, Monoclonal; D007140:Immunoglobulin Fab Fragments