Evidence map›Paper›PMID 27940383›Full record

ArticleBiomaterials2017

In vitro characterization and in vivo ultrasound molecular imaging of nucleolin-targeted microbubbles.

Hua Zhang, Elizabeth S Ingham, M Karen J Gagnon, Lisa M Mahakian, Jingfei Liu, Josquin L Foiret, Juergen K Willmann, Katherine W Ferrara

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biomaterials, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
2.8field-weighted citation impact, top 10% 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

9 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.

  1. Pooled it
  2. Molecular Ultrasound Imaging.Recent results in cancer research. Fortschritte der Krebsforschung. Progres dans les recherches sur le cancer · 2026
    Review
  3. Article
  4. Molecular Ultrasound Imaging.Nanomaterials (Basel, Switzerland) · 2020
    Review
  5. Article
  6. Low-frequency ultrasound-mediated cytokine transfection enhances T cell recruitment at local and distant tumor sites.Proceedings of the National Academy of Sciences of the United States of America · 2020
    Article
  7. Article
  8. Review
  9. 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 2 institutions in 1 country.

Hua ZhangDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Elizabeth S InghamDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
M Karen J GagnonDepartment of Environmental Health and Safety, University of California, Davis, CA, 95616, USA.
Lisa M MahakianDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Jingfei LiuDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Josquin L FoiretDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA.
Juergen K WillmannDepartment of Radiology, Stanford University, Stanford, CA, 94304, USA.
Katherine W FerraraDepartment of Biomedical Engineering, University of California, Davis, CA, 95616, USA. Electronic address: kwferrara@ucdavis.edu.
University of California, Davis · USStanford University · US

Funding

Specific and high-resolution ultrasound cancer imagingR01CA112356 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI FERRARA, KATHERINE W, FOIRET, JOSQUIN · 2005 to 2022
$6.1M
Ultrasound imaging and enhanced therapeutic responseR01CA134659 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FERRARA, KATHERINE W · 2009 to 2017
$4.4M
Image-guided ultrasound therapy and drug delivery in pancreatic cancerR01CA210553 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FERRARA, KATHERINE W · 2016 to 2020
$3.2M
Optimized ultrasound-enhanced immunotherapyR01CA199658 · NCI · UNIVERSITY OF CALIFORNIA AT DAVIS · PI FERRARA, KATHERINE W · 2015 to 2019
$2.5M
NCI NIH HHS L40 CA103838NCI NIH HHS R01 CA112356NCI NIH HHS R01 CA134659NCI NIH HHS R01 CA199658NCI NIH HHS R01 CA210553
6 · The paper itself

Abstract

Nucleolin (NCL) plays an important role in tumor vascular development. An increased endothelial expression level of NCL has been related to cancer aggressiveness and prognosis and has been detected clinically in advanced tumors. Here, with a peptide targeted to NCL (F3 peptide), we created an NCL-targeted microbubble (MB) and compared the performance of F3-conjugated MBs with non-targeted (NT) MBs both in vitro and in vivo. In an in vitro study, F3-conjugated MBs bound 433 times more than NT MBs to an NCL-expressing cell line, while pretreating cells with 0.5 mM free F3 peptide reduced the binding of F3-conjugated MBs by 84%, n = 4, p < 0.001. We then set out to create a method to extract both the tumor wash-in and wash-out kinetics and tumor accumulation following a single injection of targeted MBs. In order to accomplish this, a series of ultrasound frames (a clip) was recorded at the time of injection and subsequent time points. Each pixel within this clip was analyzed for the minimum intensity projection (MinIP) and average intensity projection (AvgIP). We found that the MinIP robustly demonstrates enhanced accumulation of F3-conjugated MBs over the range of tumor diameters evaluated here (2-8 mm), and the difference between the AvgIP and the MinIP quantifies inflow and kinetics. The inflow and clearance were similar for unbound F3-conjugated MBs, control (non-targeted) and scrambled control agents. Targeted agent accumulation was confirmed by a high amplitude pulse and by a two-dimensional Fourier Transform technique. In summary, F3-conjugated MBs provide a new imaging agent for ultrasound molecular imaging of cancer vasculature, and we have validated metrics to assess performance using low mechanical index strategies that have potential for use in human molecular imaging studies.

Indexed as

MicrobubblesUltrasonographyAnimalsCell Line, TumorFemaleHumansMiceMolecular ImagingNeoplasms, ExperimentalNucleolinPeptidesPhosphoproteinsReproducibility of ResultsRNA-Binding ProteinsSensitivity and SpecificityNucleolinPeptidesPhosphoproteinsRNA-Binding ProteinsAngiogenesisIn vivoMolecular imagingNucleolinPeptideUltrasound contrast agents

Identifiers

PMID27940383
PMCPMC5279957
OpenAlexW2551018594

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.