Pharmacokinetic analysis of the monoclonal antibody A7-neocarzinostatin conjugate administered to nude mice.
The pharmacokinetics of a disulfide linked conjugate of a murine monoclonal antibody A7 with neocarzinostatin (A7-NCS) was studied following its intravenous administration to nude mice. Disappearance of the conjugate from the circulation was biphasic: an early rapid phase was followed by a much slower phase. The conjugate was removed from the blood circulation with a half-life of 12 hr, showing nearly the same kinetics as the free antibody. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis showed that the disulfide linkage in A7-NCS was stable at least for 48 hr after administration of the conjugate to nude mice. The conjugate concentration in a human colon cancer SW1116 derived tumor reached maximum at 24 hr after injection and remained high for an additional 24 hr. The passive hemagglutination inhibition assay revealed that NCS in the conjugated form can be efficiently delivered to the target tissue. The present report indicates that A7-NCS was sufficiently stable in circulation to reach the target tumor without releasing NCS.
Kitamura
K
K
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Takahashi
T
T
Noguchi
A
A
Tsurumi
H
H
Takashina
K
K
Okuzumi
J
J
Yamaguchi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000378:metabolism*; D003110:Colonic Neoplasms / Q000378:metabolism; D004337:Drug Carriers; D004355:Drug Stability; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics; D051379:Mice; D008819:Mice, Nude / Q000378:metabolism; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging; D016719:Radioimmunodetection; D014183:Transplantation, Heterologous; D009353:Zinostatin / Q000008:administration & dosage / Q000493:pharmacokinetics*
D000911:Antibodies, Monoclonal; D004337:Drug Carriers; D007457:Iodine Radioisotopes; D009353:Zinostatin