Improved radiolabeled monoclonal antibody uptake by lavage of intraperitoneal carcinomatosis in mice.
The effect of peritoneal lavage with saline on tumor and systemic uptake of intraperitoneally administered tumor-specific (131I-5G6.4) and nonspecific (125I-UPC-10) radiolabeled monoclonal antibodies was evaluated in a nude mouse model of human intraperitoneal ovarian carcinomatosis (IP3 model). Peritoneal lavage at 2 or 6 hr postintraperitoneal antibody injection significantly improves intraperitoneal tumor/nontumor uptake ratios of specific antibody apparently by limiting systemic exposure to antibody. This enhancement tends to be more dramatic if lavage is performed within 2 hr, rather than 6 hr, of intraperitoneal antibody administration, though both times result in significant improvements in target/background ratios over no lavage. Twenty-four-hour tumor/nontumor ratios for specific antibody 5G6.4 generally are 1.5-fourfold higher following lavage than those achieved in control animals, without decreasing absolute tumor uptake of specific radiolabeled antibody. By contrast, nonspecific antibody UPC-10 binding is lower in tumor and normal tissues following lavage, with no lavage-induced improvement in tumor/nontumor ratios seen. Peritoneal lavage is a simple method to allow for specific antibody binding to accessible intraperitoneal tumors yet to limit systemic exposure thus increasing the therapeutic margin. This method may have considerable applicability in the enhancement of intraperitoneal immunoconjugate delivery to intraperitoneal tumors.
Wahl
R L
RL
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0028.
Liebert
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000032:analysis*; D002277:Carcinoma / Q000032:analysis*; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007457:Iodine Radioisotopes / Q000008:administration & dosage; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000032:analysis*; D010529:Peritoneal Cavity; D010533:Peritoneal Lavage; D010534:Peritoneal Neoplasms / Q000032:analysis*; D012965:Sodium Chloride / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D007457:Iodine Radioisotopes; D012965:Sodium Chloride