Comparative Pharmacokinetic Properties of Murine Monoclonal Antibody A7 Modified with Neocarzinostatin, Dextran and Polyethylene Glycol

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Abstract
The murinc monoclonal antibody A7 (Mab A7) was chemically modified with several macromolecnles: 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.

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