Selective transport of an anti-transferrin receptor antibody through the blood-brain barrier in vivo.
Abstract
The brain capillary endothelium, which makes up the blood-brain barrier (BBB) in vivo, expresses high concentrations of transferrin receptor, and recent studies show that an antitransferrin receptor monoclonal antibody may function as a BBB drug transport vector. The present report examines the pharmacokinetics of clearance of radiolabeled antitransferrin receptor monoclonal antibody from the bloodstream in rats in vivo, and also assesses the extent to which brain selectively extracts the antibody from the blood compared to other peripheral organs such as liver, kidney, myocardium, or lung. [125I]Mouse immunoglobulin G2a control antibody was cleared monoexponentially with a half-time of 9.8 +/- 2.3 h. The clearance of the [3H]OX-26 antitransferrin receptor antibody from blood was biexponential with half-times of 2.2 +/- 0.8 min (61 +/- 10% of clearance) and 3.9 +/- 0.2 h (39 +/- 4% of clearance). The OX-26 antibody was rapidly taken up by liver during the first 60 min after injection, but this uptake reached rapid saturation, and hepatic OX-26 content actually declined subsequent to the first hour after injection. In contrast, brain continuously extracted the OX-26 antibody from the bloodstream, and the brain volume of distribution of OX-26 reached a value 18-fold greater than the volume of distribution of the mouse immunoglobulin G2a at 5 h after injection. There was no specific uptake of the OX-26 by myocardium or lung, and minor uptake by kidney was observed that also reac…
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Transferrin receptor, insulin receptor, and leptin receptor mediate blood-to-brain transport of transferrin, insulin, and leptin across the blood-brain barrier, respectively.
“Transferrin receptor (TfR) (78, 290, 461), insulin receptor (IR) (283, 458), and leptin receptor (LEP-R) (41, 206, 699) mediate blood-to-brain transport of transferrin (iron-protein carrier), insulin, and leptin across the BBB, respectively.”
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- Authors
- Pardridge, W. M., Buciak, J. L., & Friden, P. M.
- Affiliations
- University of California, Los Angeles (US)
- ORCID
- Pardridge, W M
- Venue
- The Journal of Pharmacology and Experimental Therapeutics
- Publisher
- Elsevier BV
- Published
- 1991-10
- Volume
- 259
- Issue
- 1
- Pages
- 66-70
- ISSN
- 0022-3565 (ISSN-L)
- OpenAlex
- W2261912426
- Cited by
- 358
- References
- 0
- Citations by year
- 2026: 6 · 2025: 22 · 2024: 7 · 2023: 12 · 2022: 12 · 2021: 5 · 2020: 15 · 2019: 9 · 2018: 14 · 2017: 12 · 2016: 11 · 2015: 24 · 2014: 17 · 2013: 11 · 2012: 15
- FWCI
- 5.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed
- Funders
- National Institutes of Health (5r01ai028760-07)
- National Institute of Allergy and Infectious Diseases (R01-AI28760)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Oncology › Drug Transport and Resistance Mechanisms
- Physical Sciences › Materials Science › Biomaterials › Nanoparticle-Based Drug Delivery
- Keywords
- blood-brain barrier, transferrin receptor, antibody clearance, pharmacokinetics, brain uptake, volume of distribution, hepatic uptake, antibody saturation, brain capillary endothelium, radiolabeled antibodies
- MeSH terms
- Animals, Antibodies, Monoclonal, Blood-Brain Barrier, Capillaries, Cattle, Humans, Immunoglobulin G, Iodine Radioisotopes, Liver, Male, Metabolic Clearance Rate, Rats, Inbred Strains, Receptors, Transferrin, Mice, Rats
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