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Methods Enzymol. 2012;503:255-68. doi: 10.1016/B978-0-12-396962-0.00010-0.

Practical theoretic guidance for the design of tumor-targeting agents.

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  • 1Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.

Abstract

Theoretical analyses of targeting agent pharmacokinetics provides specific guidance with respect to desirable design objectives such as agent size, affinity, and target antigen. These analyses suggest that IgG-sized macromolecular constructs exhibit the most favorable balance between systemic clearance and vascular extravasation, resulting in maximal tumor uptake. Quantitative predictions of the effects of dose and binding affinity on tumor uptake and penetration are also provided. The single bolus dose required for saturation of xenografted tumors in mice can be predicted from knowledge of antigen expression level and metabolic half-life. The role of high binding affinity in tumor uptake can be summarized as: essential for small peptides, less important for antibodies, and negligible for nanoparticles.

Copyright © 2012 Elsevier Inc. All rights reserved.

PMID:
22230572
[PubMed - indexed for MEDLINE]
PMCID:
PMC3978464
Free PMC Article

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