Comparative pharmacokinetic properties of murine monoclonal antibody A7 modified with neocarzinostatin, dextran and polyethylene glycol.
The murine monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecules: dextran, polyethylene glycol and the anti-cancer polypeptide neocarzinostatin. The pharmacokinetic properties of the combinations were subsequently examined. Radioimmunoassay revealed that all preparations retained their antigen-binding activities. The Mab A7-neocarzinostatin conjugate was cleared from the blood circulation with a kinetic pattern almost identical to that of the parent Mab A7. Of the three preparations, Mab A7-dextran (A7-Dx) was removed the most rapidly from the circulation. Mab A7-polyethylene glycol (A7-PEG) exhibited the slowest blood clearance curve, with twice the half life of the parent Mab A7 in the circulation. In normal organ distributions, A7-Dx exhibited the highest liver, spleen and kidney uptake, and A7-PEG showed the lowest uptake, when expressed as tissue:blood ratio. Although A7-Dx exhibited lower tumor uptake, there was no significant difference among the three conjugates in tumor-bearing nude mice. A7-PEG seems to be a good candidate for targeted cancer therapy using antibody due to its high blood retention but low normal organ uptake.
Takashina
K
K
First Department of Surgery, Kyoto Prefectural University of Medicine.
Kitamura
K
K
Yamaguchi
T
T
Noguchi
A
A
Noguchi
A
A
Tsurumi
H
H
Takahashi
T
T
D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000378:metabolism*; D003911:Dextrans / Q000737:chemistry; D008657:Metabolic Clearance Rate; D051379:Mice; D009374:Neoplasms, Experimental / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry; D014018:Tissue Distribution; D009353:Zinostatin / Q000737:chemistry
D000911:Antibodies, Monoclonal; D003911:Dextrans; D011092:Polyethylene Glycols; D009353:Zinostatin