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Effect of Dose, Molecular Size, and Binding Affinity on Uptake of Antibodies

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Drug Targeting

Part of the book series: Methods in Molecular Medicine™ ((MIMM,volume 25))

Abstract

The huge molecular radius of immunoglobulins would seem to be a major drawback for the targeting of solid tumors, because of slow extravasation into tumor interstitium and along plasma half-life. The permeability of normal continuous capillary endothelia to intravascular solutes of different molecular sizes has been determined in animals, mainly for macromolecules, and different sources give data consistent with the graph in Fig. 1 (1–3). The position of whole antibodies (IgG, mol wt 150 kDa and effective molecular radius 5.5 nm) is well to the right of albumen (66 kDa and 3.5 nm), and they are therefore very slowly extravasated in normal tissues. A F(ab’)2 fragment (100 kDa, 5.06 nm) should not extravasate much faster than the intact molecule on this basis and a monomeric Fab’ fragment (50 kDa, 3.48 nm) still has quite a high molecular radius (4), so a much smaller molecule would be necessary to equilibrate very quickly with extracellular fluid (ECF).

Relationship between molecular radius and permeability/surface area product for intact capillaries.

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  1. Department of Clinical Oncology, Derbyshire Royal Infirmary, Derby, UK

    Gillian D. Thomas

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  1. PolyMASC Pharmaceuticals, London, UK

    G. E. Francis

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Thomas, G.D. (2000). Effect of Dose, Molecular Size, and Binding Affinity on Uptake of Antibodies. In: Francis, G.E., Delgado, C. (eds) Drug Targeting. Methods in Molecular Medicine™, vol 25. Humana Press. https://doi.org/10.1385/1-59259-075-6:115

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  • DOI: https://doi.org/10.1385/1-59259-075-6:115

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