Evidence map›Paper›PMID 26541778›Full record

ArticleJournal of nuclear medicine : official publication, Society of Nuclear Medicine2016

PET Imaging of VEGFR-2 Expression in Lung Cancer with 64Cu-Labeled Ramucirumab.

Haiming Luo, Christopher G England, Stephen A Graves, Haiyan Sun, Glenn Liu, Robert J Nickles, Weibo Cai

Open access · bronzeAbstract read
In one paragraph

Article in Journal of nuclear medicine : official publication, Society of Nuclear Medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.4field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
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  5. Radiopharmaceuticals and their applications in medicine.Signal transduction and targeted therapy · 2025
    Review
  6. Review
  7. Review
  8. Radionuclide-based theranostics - a promising strategy for lung cancer.European journal of nuclear medicine and molecular imaging · 2023
    Review
  9. Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
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  17. Article
  18. Review
  19. Immuno-PET imaging of VEGFR-2 expression in prostate cancer withAmerican journal of cancer research · 2019
    Article
  20. PET Imaging of Receptor Tyrosine Kinases in Cancer.Molecular cancer therapeutics · 2018
    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

7 authors at 2 institutions in 1 country.

Haiming LuoDepartment of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
Christopher G EnglandDepartment of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin; and.
Stephen A GravesDepartment of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin; and.
Haiyan SunDepartment of Radiology, University of Wisconsin-Madison, Madison, Wisconsin.
Glenn LiuUniversity of Wisconsin Carbone Cancer Center, Madison, Wisconsin.
Robert J NicklesDepartment of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin; and.
Weibo CaiDepartment of Radiology, University of Wisconsin-Madison, Madison, Wisconsin Department of Medical Physics, University of Wisconsin-Madison, Madison, Wisconsin; and University of Wisconsin Carbone Cancer Center, Madison, Wisconsin wcai@uwhealth.org.
University of Wisconsin–Madison · USUniversity of Wisconsin Carbone Cancer Center · US

Funding

UW COMPREHENSIVE CANCER CENTER SUPPORTP30CA014520 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Christian Capitini · 1985 to 2026
$142.6M
U.W. RADIOLOGICAL SCIENCES TRAINING PROGRAMT32CA009206 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI Bryan Patrick Bednarz · 1985 to 2026
$12.1M
Novel Combination Therapy for Prostate CancerR01CA169365 · NCI · UNIVERSITY OF WISCONSIN-MADISON · PI CAI, WEIBO · 2013 to 2015
$903k
NCI NIH HHS 1R01CA169365NCI NIH HHS P30 CA014520NCI NIH HHS P30CA014520NCI NIH HHS R01 CA169365NCI NIH HHS T32 CA009206NCI NIH HHS T32CA009206
6 · The paper itself

Abstract

unlabelledLung cancer accounts for 17% of cancer-related deaths worldwide, and most patients present with locally advanced or metastatic disease. Novel PET imaging agents for assessing vascular endothelial growth factor receptor-2 (VEGFR-2) expression can be used for detecting VEGFR-2-positive malignancies and subsequent monitoring of therapeutic response to VEGFR-2-targeted therapies. Here, we report the synthesis and characterization of an antibody-based imaging agent for PET imaging of VEGFR-2 expression in vivo.

methodsRamucirumab (named RamAb), a fully humanized IgG1 monoclonal antibody, was conjugated to 2-S-(4-isothiocyanatobenzyl)-1,4,7-triazacyclononane-1,4,7-triacetic acid (p-SCN-Bn-NOTA) and labeled with (64)Cu. Flow cytometry analysis and microscopy studies were performed to compare the VEGFR-2 binding affinity of RamAb and NOTA-RamAb. PET imaging and biodistribution studies were performed in nude mice bearing HCC4006 and A549 xenograft tumors. Ex vivo histopathology was performed to elucidate the expression patterns of VEGFR-2 in different tissues and organs to validate in vivo results.

resultsFlow cytometry examination revealed the specific binding capacity of fluorescein isothiocyanate-RamAb to VEGFR-2, and no difference in VEGFR-2 binding affinity was seen between RamAb and NOTA-RamAb. After being labeled with (64)Cu, PET imaging revealed specific and prominent uptake of (64)Cu-NOTA-RamAb in VEGFR-2-positive HCC4006 tumors (9.4 ± 0.5 percentage injected dose per gram at 48 h after injection; n = 4) and significantly lower uptake in VEGFR-2-negative A549 tumors (4.3 ± 0.2 percentage injected dose per gram at 48 h after injection; n = 3). Blocking experiments revealed significantly lower uptake in HCC4006 tumors, along with histology analysis, further confirming the VEGFR-2 specificity of (64)Cu-NOTA-RamAb.

conclusionThis study provides initial evidence that (64)Cu-NOTA-RamAb can function as a PET imaging agent for visualizing VEGFR-2 expression in vivo, which may also find potential applications in monitoring the treatment response of VEGFR-2-targeted cancer therapy.

Indexed as

Antibodies, MonoclonalRadiopharmaceuticalsAnimalsAntibodies, Monoclonal, HumanizedCell Line, TumorCopper RadioisotopesHeterocyclic CompoundsHeterocyclic Compounds, 1-RingHumansIsotope LabelingLung NeoplasmsMiceMice, NudeMolecular ImagingPositron-Emission TomographyRamucirumab1,4,7-triazacyclononane-N,N',N''-triacetic acidAntibodies, MonoclonalAntibodies, Monoclonal, HumanizedCopper RadioisotopesHeterocyclic CompoundsHeterocyclic Compounds, 1-RingKDR protein, humanRadiopharmaceuticalsRamucirumabVascular Endothelial Growth Factor Receptor-264Cumolecular imagingpositron emission tomography (PET)ramucirumabvascular endothelial growth factor receptor-2 (VEGFR-2)

Identifiers

PMID26541778
PMCPMC4738068
OpenAlexW2190021054

What OpenQuestion holds

Textmetadata
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.