Evidence map›Paper›PMID 24572100›Full record

ArticlemAbs

Quantitative cumulative biodistribution of antibodies in mice: effect of modulating binding affinity to the neonatal Fc receptor.

Victor Yip, Enzo Palma, Devin B Tesar, Eduardo E Mundo, Daniela Bumbaca, Elizabeth K Torres, Noe A Reyes, Ben Q Shen, Paul J Fielder, Saileta Prabhu and 2 more

Open access · goldAbstract read
In one paragraph

Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
52citing papers in PubMed, 1 pooled it
7.2field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

52 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.

  1. Pooled it
  2. Predicting tumour and organ dose in α-radiopharmaceutical therapy: aEuropean journal of nuclear medicine and molecular imaging · 2026
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  7. Review
  8. Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Serum immunoglobulin and the threshold of Fc receptor-mediated immune activation.Biochimica et biophysica acta. General subjects · 2023
    Review
  15. Article
  16. Evaluating the Targeting of aInternational journal of molecular sciences · 2023
    Article
  17. Article
  18. Optimizing Immuno-PET Imaging of Tumor PD-L1 Expression: Pharmacokinetic, Biodistribution, and Dosimetric Comparisons ofJournal of nuclear medicine : official publication, Society of Nuclear Medicine · 2022
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Victor YipPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Enzo PalmaPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Devin B TesarDrug Delivery Department; Pharma Technical Development, Genentech; South San Francisco, CA USA.
Eduardo E MundoPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Daniela BumbacaPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Elizabeth K TorresNon-Clinical Operations; Genentech Research & Early Development; South San Francisco, CA USA.
Noe A ReyesPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Ben Q ShenPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Paul J FielderPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Saileta PrabhuPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Leslie A KhawliPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
C Andrew BoswellPreclinical and Translational Pharmacokinetics; Genentech Research & Early Development; South San Francisco, CA USA.
Kaiser Permanente South San Francisco Medical Center · USCytokinetics (United States) · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The neonatal Fc receptor (FcRn) plays an important and well-known role in antibody recycling in endothelial and hematopoietic cells and thus it influences the systemic pharmacokinetics (PK) of immunoglobulin G (IgG). However, considerably less is known about FcRn's role in the metabolism of IgG within individual tissues after intravenous administration. To elucidate the organ distribution and gain insight into the metabolism of humanized IgG1 antibodies with different binding affinities FcRn, comparative biodistribution studies in normal CD-1 mice were conducted. Here, we generated variants of herpes simplex virus glycoprotein D-specific antibody (humanized anti-gD) with increased and decreased FcRn binding affinity by genetic engineering without affecting antigen specificity. These antibodies were expressed in Chinese hamster ovary cell lines, purified and paired radiolabeled with iodine-125 and indium-111. Equal amounts of I-125-labeled and In-111-labeled antibodies were mixed and intravenously administered into mice at 5 mg/kg. This approach allowed us to measure both the real-time IgG uptake (I-125) and cumulative uptake of IgG and catabolites (In-111) in individual tissues up to 1 week post-injection. The PK and distribution of the wild-type IgG and the variant with enhanced binding for FcRn were largely similar to each other, but vastly different for the rapidly cleared low-FcRn-binding variant. Uptake in individual tissues varied across time, FcRn binding affinity, and radiolabeling method. The liver and spleen emerged as the most concentrated sites of IgG catabolism in the absence of FcRn protection. These data provide an increased understanding of FcRn's role in antibody PK and catabolism at the tissue level.

Indexed as

AnimalsAnimals, NewbornAntibodies, Monoclonal, HumanizedCHO CellsCricetinaeCricetulusFemaleGenetic VariationHumansImmunoglobulin GIndium RadioisotopesIodine RadioisotopesMiceProteolysisReceptors, FcTissue DistributionAntibodies, Monoclonal, HumanizedImmunoglobulin GIndium RadioisotopesIodine RadioisotopesReceptors, FcbiodistributionFcRnindiummetabolismpharmacokineticsradiolabeled

Identifiers

PMID24572100
PMCPMC4011913
OpenAlexW1964936749

What OpenQuestion holds

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LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.