Antibody biodistribution coefficients: Inferring tissue concentrations of monoclonal antibodies based on the plasma concentrations in several preclinical species and human
Open accessAbstract
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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In preclinical species and humans, mAbs are known to have minimal brain penetration, at around 0.1-0.4% of mAb plasma concentration.
“In preclinical species and humans, mAbs are known to have minimal brain penetration, at around 0.1–0.4% of mAb plasma concentration35,36.”
From A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings (2024) · cites this paper as [36]
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- Authors
- Shah, D. K., & Betts, A. M.
- Affiliations
- Pfizer (United States) (US)
- Corresponding author
- Shah, Dhaval K.
- Venue
- mAbs
- Publisher
- Informa UK Limited
- Published
- 2013-03
- Volume
- 5
- Issue
- 2
- Pages
- 297-305
- ISSN
- 1942-0862 (ISSN-L)
- 1942-0870
- PMC
- PMC3893240
- 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
- gold
- doi.org
- 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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