Intraperitoneal delivery of monoclonal antibodies: Enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody

Richard L. Wahl, Susan Fisher

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Radiolabeled monoclonal antibodies (MAb) delivered intraperitoneally expose cells in contact with peritoneal fluid to considerably higher levels of MAb than if the MAb dose were given intravenously. This regional delivery advantage for intact MAb is present mainly due to the relatively slow exit of MAb from the peritoneal fluid to the blood. Eventually, following i.p. injection, blood levels of MAb rise resulting in exposure of the animal to high systemic MAb levels and potential toxicity. In this series of experiments, systemic exposure was minimized by the administration of unlabeled goat polyclonal anti-mouse antibody intravenously from 1 1 2 to 6 h following i.p. MAb injection. This maneuver results in the formation of immune complexes with their subsequent clearance and dehalogenation by the reticuloendothelial system, thus minimizing systemic MAb exposure. This approach, of increasing systemic clearance of MAb, did not alter intraperitoneal MAb levels and thus significantly increased the regional delivery advantage to the peritoneal cavity by 70-100%. This approach provides an immunologic rationale for the further enhancement of MAb delivery to i.p. foci of malignant disease and may have diagnostic and therapeutic utility.

Original languageEnglish
Pages (from-to)611-615
Number of pages5
JournalInternational Journal of Radiation Applications and Instrumentation.
Volume14
Issue number6
DOIs
StatePublished - 1987
Externally publishedYes

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