PMID: 8595158Feb 1, 1996Paper

Pharmacokinetic analysis of the microscopic distribution of enzyme-conjugated antibodies and prodrugs: comparison with experimental data

British Journal of Cancer
L T Baxter, R K Jain

Abstract

A mathematical model was developed to improve understanding of the biodistribution and microscopic profiles of drugs and prodrugs in a system using enzyme-conjugated antibodies as part of a two-step method for cancer treatment. The use of monoclonal antibodies alone may lead to heterogeneous uptake within the tumour tissue; the use of a second, low molecular weight agent may provide greater penetration into tumour tissue. This mathematical model was used to describe concentration profiles surrounding individual blood vessels within a tumour. From these profiles the area under the curve and specificity ratios were determined. By integrating these results spatially, average tissue concentrations were determined and compared with experimental results from three different systems in the literature; two using murine antibodies and one using humanised fusion proteins. The maximum enzyme conversion rate (Vmax) and the residual antibody concentration in the plasma and normal tissue were seen to be key determinants of drug concentration and drug-prodrug ratios in the tumour and other organs. Thus, longer time delays between the two injections, clearing the antibody from the blood stream and the use of 'weaker' enzymes (lower Vmax) will ...Continue Reading

Citations

Jul 1, 1996·Annals of Biomedical Engineering·R K Jain
Nov 10, 2001·Annual Review of Biomedical Engineering·R K Jain
Oct 3, 2003·Journal of Cellular Biochemistry·Paul Winnard, Venu Raman
Feb 12, 2015·Annals of Biomedical Engineering·Triantafyllos StylianopoulosRakesh K Jain
Apr 29, 1998·Diseases of the Colon and Rectum·L Stocchi, H Nelson
Mar 22, 2008·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Lanyan Fang, Duxin Sun
Feb 19, 2017·Molecular Imaging and Biology : MIB : the Official Publication of the Academy of Molecular Imaging·Kelly D OrcuttRobert A Beckman
Oct 9, 2020·Scientific Reports·Yu Tang, Yanguang Cao
Mar 10, 2020·Methods : a Companion to Methods in Enzymology·Myrianthi HadjicharalambousVasileios Vavourakis

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