TY - JOUR
T1 - Intraperitoneal delivery of monoclonal antibodies
T2 - Enhanced regional delivery advantage using intravenous unlabeled anti-mouse antibody
AU - Wahl, Richard L.
AU - Fisher, Susan
N1 - Funding Information:
Acknowledgements-Thisin vestigatiown as supportedb y PHS GrantN o. CA41531-01a nd CA33802-04a wardedb v the National Cancer Institute,D HHS. Thanks to Mrs Michele Bell for excellents ecretarial assistance.
PY - 1987
Y1 - 1987
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=45949129086&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45949129086&partnerID=8YFLogxK
U2 - 10.1016/0883-2897(87)90034-1
DO - 10.1016/0883-2897(87)90034-1
M3 - Article
C2 - 3429242
AN - SCOPUS:45949129086
SN - 0969-8051
VL - 14
SP - 611
EP - 615
JO - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
JF - International journal of radiation applications and instrumentation. Part B, Nuclear medicine and biology
IS - 6
ER -