Cited by 262Monoclonal and Polyclonal Antibodies ResearchBiosimilars and Bioanalytical MethodsRadiopharmaceutical Chemistry and Applications

Antibody biodistribution coefficients: Inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human

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Shah, Dhaval K., Betts, Alison M.·2013·mAbs

Abstract

Tissue vs. plasma concentration profiles have been generated from a physiologically-based pharmacokinetic model of monoclonal antibody (mAb). Based on the profiles, we hypothesized that a linear relationship between the plasma and tissue concentrations of non-binding mAbs could exist; and that the relationship may be generally constant irrespective of the absolute mAb concentration, time, and animal species being analyzed. The hypothesis was verified for various tissues in mice, rat, monkey, and human using mAb or antibody-drug conjugate tissue distribution data collected from diverse literature. The relationship between the plasma and various tissue concentrations was mathematically characterized using the antibody biodistribution coefficient (ABC). Estimated ABC values suggest that typically the concentration of mAb in lung is 14.9%, heart 10.2%, kidney 13.7%, muscle 3.97%, skin 15.7%, small intestine 5.22%, large intestine 5.03%, spleen 12.8%, liver 12.1%, bone 7.27%, stomach 4.98%, lymph node 8.46%, adipose 4.78%, brain 0.351%, pancreas 6.4%, testes 5.88%, thyroid 67.5% and thymus is 6.62% of the plasma concentration. The validity of using the ABC to predict mAb concentrations in different tissues of mouse, rat, monkey, and human species was evaluated by generating validation data sets, which demonstrated that predicted concentrations were within 2-fold of the observed concentrations. The use of ABC to infer tissue concentrations of mAbs and related molecules provides a valuable tool for investigating preclinical or clinical disposition of these molecules. It can also help eliminate or optimize biodistribution studies, and interpret efficacy or toxicity of the drug in a particular tissue.

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Crossref · 10.4161/mabs.23684

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Authors
Shah, D. K., & Betts, A. M.
Affiliations
Pfizer (United States) (US)
Corresponding author
Shah, Dhaval K.
Venue
mAbs
Published
2013-03
Volume
5
Issue
2
Pages
297-305
ISSN
  • 1942-0862 (ISSN-L)
  • 1942-0870
OpenAlex
W2328527542
Cited by
262
References
36
Citations by year
2026: 24 · 2025: 34 · 2024: 28 · 2023: 20 · 2022: 30 · 2021: 26 · 2020: 17 · 2019: 22 · 2018: 13 · 2017: 16 · 2016: 9 · 2015: 15 · 2014: 8
FWCI
8.28
Type
journal article
Language
en
Open access
Locations
  • mAbs (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
  • Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiopharmaceutical Chemistry and Applications
Keywords
monoclonal antibodies, physiologically based pharmacokinetic modeling, antibody-drug conjugates, tissue distribution, interspecies extrapolation
MeSH terms
Animals, Antibodies, Monoclonal, Humans, Kidney, Lung, Models, Biological, Skin, Spleen, Tissue Distribution, Mice, Rats

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