Evidence map›Paper›PMID 27570547›Full record

ArticleTheranostics2016

Ultrasound Molecular Imaging of the Breast Cancer Neovasculature using Engineered Fibronectin Scaffold Ligands: A Novel Class of Targeted Contrast Ultrasound Agent.

Lotfi Abou-Elkacem, Katheryne E Wilson, Sadie M Johnson, Sayan M Chowdhury, Sunitha Bachawal, Benjamin J Hackel, Lu Tian, Jürgen K Willmann

Open access · goldAbstract read
In one paragraph

Article in Theranostics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

23 citing papers in PubMed, 41 citations in OpenAlex.

  1. Review
  2. Review
  3. Molecular Ultrasound Imaging.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026
    Review
  4. Stimuli-Responsive Materials for Biomedical Applications.Advanced materials (Deerfield Beach, Fla.) · 2025
    Review
  5. Article
  6. Antioxidant, Enzyme, and HAntioxidants (Basel, Switzerland) · 2022
    Article
  7. Review
  8. Molecular Ultrasound Imaging.Nanomaterials (Basel, Switzerland) · 2020
    Review
  9. Article
  10. Article
  11. Efficacy of Affibody-Based Ultrasound Molecular Imaging of Vascular B7-H3 for Breast Cancer Detection.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020
    Article
  12. Review
  13. Article
  14. Article
  15. Review
  16. Thy1-Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Ductal Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018
    Article
  17. Article
  18. Article
  19. Article
  20. 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 4 institutions in 1 country.

Lotfi Abou-Elkacem1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California, USA;
Katheryne E Wilson1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California, USA;
Sadie M Johnson2. Department of Chemical Engineering and Materials Science, University of Minnesota, Minnesota, USA;
Sayan M Chowdhury1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California, USA;
Sunitha Bachawal1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California, USA;
Benjamin J Hackel2. Department of Chemical Engineering and Materials Science, University of Minnesota, Minnesota, USA;
Lu Tian3. Department of Health, Research & Policy, Stanford University, Stanford, California, USA.
Jürgen K Willmann1. Department of Radiology, Molecular Imaging Program at Stanford, Stanford University, School of Medicine, Stanford, California, USA;
Stanford University · USStanford Medicine · USUniversity of Minnesota · USUniversity of Minnesota System · US

Funding

Translational Oncology Research Program (Project-005)P30CA124435 · NCI · STANFORD UNIVERSITY · PI Melinda L. Telli · 2007 to 2026
$71.4M
Quantification and monitoring inflammation in IBD with Molecular UltrasoundR01DK092509 · NIDDK · STANFORD UNIVERSITY · PI HARGREAVES, BRIAN ANDREW · 2012 to 2016
$2.4M
Molecular Ultrasound for Early Breast Cancer DetectionR01CA155289 · NCI · STANFORD UNIVERSITY · PI WILLMANN, JUERGEN KARL · 2011 to 2015
$1.6M
Molecular Spectroscopic Photoacoustic Imaging for Breast Lesion CharacterizationR21EB022214 · NIBIB · STANFORD UNIVERSITY · PI WILSON, KATHERYNE E · 2016 to 2017
$439k
NCI NIH HHS P30 CA124435NCI NIH HHS R01 CA155289NIBIB NIH HHS R21 EB022214NIDDK NIH HHS R01 DK092509
6 · The paper itself

Abstract

Molecularly-targeted microbubbles (MBs) are increasingly being recognized as promising contrast agents for oncological molecular imaging with ultrasound. With the detection and validation of new molecular imaging targets, novel binding ligands are needed that bind to molecular imaging targets with high affinity and specificity. In this study we assessed a novel class of potentially clinically translatable MBs using an engineered 10(th) type III domain of human-fibronectin (MB-FN3VEGFR2) scaffold-ligand to image VEGFR2 on the neovasculature of cancer. The in vitro binding of MB-FN3VEGFR2 to a soluble VEGFR2 was assessed by flow-cytometry (FACS) and binding to VEGFR2-expressing cells was assessed by flow-chamber cell attachment studies under flow shear stress conditions. In vivo binding of MB-FN3VEGFR2 was tested in a transgenic mouse model (FVB/N Tg(MMTV/PyMT634Mul) of breast cancer and control litter mates with normal mammary glands. In vitro FACS and flow-chamber cell attachment studies showed significantly (P<0.01) higher binding to VEGFR2 using MB-FN3VEGFR2 than control agents. In vivo ultrasound molecular imaging (USMI) studies using MB-FN3VEGFR2 demonstrated specific binding to VEGFR2 and was significantly higher (P<0.01) in breast cancer compared to normal breast tissue. Ex vivo immunofluorescence-analysis showed significantly (P<0.01) increased VEGFR2-expression in breast cancer compared to normal mammary tissue. Our results suggest that MBs coupled to FN3-scaffolds can be designed and used for USMI of breast cancer neoangiogenesis. Due to their small size, stability, solubility, the lack of glycosylation and disulfide bonds, FN3-scaffolds can be recombinantly produced with the advantage of generating small, high affinity ligands in a cost efficient way for USMI.

Indexed as

MicrobubblesAnimalsBreast NeoplasmsContrast MediaFibronectinsHumansMiceMice, TransgenicMolecular ImagingNeovascularization, PathologicProtein BindingUltrasonographyVascular Endothelial Growth Factor Receptor-2Contrast MediaFibronectinsKDR protein, humanVascular Endothelial Growth Factor Receptor-2Ultrasound molecular imaging, breast cancer, vascular endothelial growth factor receptor type 2, fibronectin scaffold, protein engineeringyeast display.

Identifiers

PMID27570547
PMCPMC4997233
OpenAlexW2466066844

What OpenQuestion holds

Textmetadata
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.