Evidence map›Paper›PMID 25143449›Full record

ArticleMolecular cancer therapeutics2014

Anti-MET immunoPET for non-small cell lung cancer using novel fully human antibody fragments.

Keyu Li, Richard Tavaré, Kirstin A Zettlitz, Shannon M Mumenthaler, Parag Mallick, Yu Zhou, James D Marks, Anna M Wu

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
2.7field-weighted citation impact, top 11% 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

18 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Radionuclide-based theranostics - a promising strategy for lung cancer.European journal of nuclear medicine and molecular imaging · 2023
    Review
  5. Article
  6. Review
  7. Review
  8. Review
  9. Review
  10. PET Imaging of Receptor Tyrosine Kinases in Cancer.Molecular cancer therapeutics · 2018
    Review
  11. Article
  12. Review
  13. Article
  14. European journal of nuclear medicine and molecular imaging · 2017
    Article
  15. Nanoparticles and radiotracers: advances toward radionanomedicine.Wiley interdisciplinary reviews. Nanomedicine and nanobiotechnology · 2016
    Review
  16. Article
  17. Review
  18. Article
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

8 authors at 3 institutions in 1 country.

Keyu LiDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California.
Richard TavaréDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California.
Kirstin A ZettlitzDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California.
Shannon M MumenthalerCenter for Applied Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California.
Parag MallickCenter for Applied Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California. Department of Radiology, School of Medicine, Stanford University, Stanford, California.
Yu ZhouDepartment of Anesthesia, University of California, San Francisco, San Francisco General Hospital, San Francisco, California.
James D MarksDepartment of Anesthesia, University of California, San Francisco, San Francisco General Hospital, San Francisco, California.
Anna M WuDepartment of Molecular and Medical Pharmacology, Crump Institute for Molecular Imaging, David Geffen School of Medicine at UCLA, Los Angeles, California. awu@mednet.ucla.edu.
Institute for Molecular Medicine · USSan Francisco General Hospital · USUniversity of Southern California · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
Pilot ProjectsU54CA151459 · NCI · STANFORD UNIVERSITY · PI GAMBHIR, SANJIV S · 2010 to 2014
$12.6M
NCI NIH HHS CA016042NCI NIH HHS P30 CA016042NCI NIH HHS U54 CA151459
6 · The paper itself

Abstract

MET, the receptor of hepatocyte growth factor, plays important roles in tumorigenesis and drug resistance in numerous cancers, including non-small cell lung cancer (NSCLC). As increasing numbers of MET inhibitors are being developed for clinical applications, antibody fragment-based immunopositron emission tomography (immunoPET) has the potential to rapidly quantify in vivo MET expression levels for drug response evaluation and patient stratification for these targeted therapies. Here, fully human single-chain variable fragments (scFvs) isolated from a phage display library were reformatted into bivalent cys-diabodies (scFv-cys dimers) with affinities to MET ranging from 0.7 to 5.1 nmol/L. The candidate with the highest affinity, H2, was radiolabeled with (89)Zr for immunoPET studies targeting NSCLC xenografts: low MET-expressing Hcc827 and the gefitinib-resistant Hcc827-GR6 with 4-fold MET overexpression. ImmunoPET at as early as 4 hours after injection produced high-contrast images, and ex vivo biodistribution analysis at 20 hours after injection showed about 2-fold difference in tracer uptake levels between the parental and resistant tumors (P < 0.01). Further immunoPET studies using a larger fragment, the H2 minibody (scFv-CH3 dimer), produced similar results at later time points. Two of the antibody clones (H2 and H5) showed in vitro growth inhibitory effects on MET-dependent gefitinib-resistant cell lines, whereas no effects were observed on resistant lines lacking MET activation. In conclusion, these fully human antibody fragments inhibit MET-dependent cancer cells and enable rapid immunoPET imaging to assess MET expression levels, showing potential for both therapeutic and diagnostic applications.

Indexed as

AnimalsAntibodies, MonoclonalCarcinoma, Non-Small-Cell LungCell Transformation, NeoplasticFemaleHeterograftsHumansImmunoglobulin FragmentsLung NeoplasmsMiceMice, SCIDPositron-Emission TomographyProto-Oncogene Proteins c-metRadioisotopesRadiopharmaceuticalsZirconiumAntibodies, MonoclonalImmunoglobulin FragmentsMET protein, humanProto-Oncogene Proteins c-metRadioisotopesRadiopharmaceuticalsZirconium

Identifiers

PMID25143449
PMCPMC4221648
OpenAlexW2131619253

What OpenQuestion holds

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LicenceTDM
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.