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Optimal tumor targeting by antibodies: Development of a mathematical model

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Abstract

A mathematical model has been developed to optimize tumor targeting with labeled antibodies. The model is compartmental and nonlinear, incorporating saturable binding. Published parameter values have been used in the model, and the resulting stiff differential equations have been solved using FACSIMILE, a computer package that can simulate very stiff differential systems. Results show that successful tumor targeting depends on an optimal combination of antibody dose, affinity, and molecular size. The model has allowed an assessment to be made of the complicated and interrelated dynamic relationships that these factors have on tumor targeting. It has also offered an explanation for previously unsatisfactory results from tumor targeting with labeled antibodies. The structural identifiability of the model parameters is also analyzed and it is shown that, with the prior knowledge of some parameters which is likely in practice, the remaining model parameters are uniquely identifiable.

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Author notes

  1. Gillian D. Thomas

    Present address: Department of Radiotherapy and Oncology, Royal Marsden Hospital, SM2 5PT, Sutton, Surrey, England

Authors and Affiliations

  1. Department of Engineering, University of Warwick, CV4 7AL, Coventry, England

    Michael J. Chappell & Keith R. Godfrey

  2. Immunodiagnostic Research Laboratory, Department of Immunology, University of Birmingham Medical School, B15 2TJ, Birmingham, England

    Gillian D. Thomas & Arthur R. Bradwell

Authors
  1. Michael J. Chappell
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  2. Gillian D. Thomas
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  3. Keith R. Godfrey
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  4. Arthur R. Bradwell
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Chappell, M.J., Thomas, G.D., Godfrey, K.R. et al. Optimal tumor targeting by antibodies: Development of a mathematical model. Journal of Pharmacokinetics and Biopharmaceutics 19, 227–260 (1991). https://doi.org/10.1007/BF01073870

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  • DOI: https://doi.org/10.1007/BF01073870

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