Synthesis and biodistribution of immunoconjugates of a human IgM and polymeric drug carriers

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Hoes, C.J.T. and Grootoonk, J. and Feijen, J. and Boon, P.J. and Kaspersen, F. and Loeffen, P. and Schlachter, I. and Winters, M. and Bos, E.S. (1992) Synthesis and biodistribution of immunoconjugates of a human IgM and polymeric drug carriers. Journal of Controlled Release, 19 (1-3). pp. 59-76. ISSN 0168-3659

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Abstract:The synthesis and purification of radiolabelled immunoconjugates, composed of a human IgM monoclonal antibody directed against an intracellular tumour-associated antigen and either poly (alpha-L-glutamic acid) (PGA) or poly[N5-(2-hydroxyethyl)-L-glutamine] (PHEG) is described. Coupling of polymers to the antibody was performed through disulfide bond formation involving a single thiol group at the C-terminus of the polymer chain and 2-pyridyldisulfide groups introduced onto the antibody. The antibody was iodinated with 131I before conjugation. The polymers contained tyrosinamide in a low degree of substitution and were radiolabelled with 125I. 125I-labelled PGA and PHEG were found to be stable for at least 3 days in murine and human plasma. The biodistribution in mice of the doubly labelled immunoconjugates was studied and was compared with the pharmacokinetics of the individual components.

PHEG showed a relatively slow blood clearance, the half-life being approximately 10 h with low uptake in liver, kidneys and spleen. PGA was rapidly cleared from the circulation and was significantly taken up in liver, kidneys and spleen. The biodistribution of both immunoconjugates was indistinguishable from that of the IgM proper, with plasma half-lives of approximately 6 h, indicating that the pharmacokinetic properties of the immunoconjugates are largely determined by the antibody part.
Item Type:Article
Copyright:© 1992 Elsevier Science
Faculty:
Science and Technology (TNW)
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Link to this item:http://purl.utwente.nl/publications/9603
Official URL:http://dx.doi.org/10.1016/0168-3659(92)90065-Y
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Metis ID: 105245