Skip to main content

Main menu

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Corporate & Special Sales
    • Journal Claims
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Permissions
    • Advertisers
    • Continuing Education
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI

User menu

  • Subscribe
  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Journal of Nuclear Medicine
  • SNMMI
    • JNM
    • JNMT
    • SNMMI Journals
    • SNMMI
  • Subscribe
  • My alerts
  • Log in
  • My Cart
Journal of Nuclear Medicine

Advanced Search

  • Home
  • Content
    • Current
    • Ahead of print
    • Past Issues
    • JNM Supplement
    • SNMMI Annual Meeting Abstracts
  • Subscriptions
    • Subscribers
    • Institutional and Non-member
    • Rates
    • Corporate & Special Sales
    • Journal Claims
  • Authors
    • Submit to JNM
    • Information for Authors
    • Assignment of Copyright
    • AQARA requirements
  • Info
    • Permissions
    • Advertisers
    • Continuing Education
  • About
    • About Us
    • Editorial Board
    • Contact Information
  • More
    • Alerts
    • Feedback
    • Help
    • SNMMI Journals
  • Follow JNM on Twitter
  • Visit JNM on Facebook
  • Join JNM on LinkedIn
  • Subscribe to our RSS feeds
OtherBASIC SCIENCE INVESTIGATIONS

Targeted Contrast-Enhanced Ultrasound Imaging of Tumor Angiogenesis with Contrast Microbubbles Conjugated to Integrin-Binding Knottin Peptides

Jürgen K. Willmann, Richard H. Kimura, Nirupama Deshpande, Amelie M. Lutz, Jennifer R. Cochran and Sanjiv S. Gambhir
Journal of Nuclear Medicine March 2010, 51 (3) 433-440; DOI: https://doi.org/10.2967/jnumed.109.068007
Jürgen K. Willmann
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Richard H. Kimura
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nirupama Deshpande
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Amelie M. Lutz
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jennifer R. Cochran
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Sanjiv S. Gambhir
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • PDF
Loading

Abstract

Targeted contrast-enhanced ultrasound imaging is increasingly being recognized as a powerful imaging tool for the detection and quantification of tumor angiogenesis at the molecular level. The purpose of this study was to develop and test a new class of targeting ligands for targeted contrast-enhanced ultrasound imaging of tumor angiogenesis with small, conformationally constrained peptides that can be coupled to the surface of ultrasound contrast agents. Methods: Directed evolution was used to engineer a small, disulfide-constrained cystine knot (knottin) peptide that bound to αvβ3 integrins with a low nanomolar affinity (KnottinIntegrin). A targeted contrast-enhanced ultrasound imaging contrast agent was created by attaching KnottinIntegrin to the shell of perfluorocarbon-filled microbubbles (MB-KnottinIntegrin). A knottin peptide with a scrambled sequence was used to create control microbubbles (MB-KnottinScrambled). The binding of MB-KnottinIntegrin and MB-KnottinScrambled to αvβ3 integrin-positive cells and control cells was assessed in cell culture binding experiments and compared with that of microbubbles coupled to an anti-αvβ3 integrin monoclonal antibody (MBαvβ3) and microbubbles coupled to the peptidomimetic agent c(RGDfK) (MBcRGD). The in vivo imaging signals of contrast-enhanced ultrasound with the different types of microbubbles were quantified in 42 mice bearing human ovarian adenocarcinoma xenograft tumors by use of a high-resolution 40-MHz ultrasound system. Results: MB-KnottinIntegrin attached significantly more to αvβ3 integrin-positive cells (1.76 ± 0.49 [mean ± SD] microbubbles per cell) than to control cells (0.07 ± 0.006). Control MB-KnottinScrambled adhered less to αvβ3 integrin-positive cells (0.15 ± 0.12) than MB-KnottinIntegrin. After blocking of integrins, the attachment of MB-KnottinIntegrin to αvβ3 integrin-positive cells decreased significantly. The in vivo ultrasound imaging signal was significantly higher after the administration of MB-KnottinIntegrin than after the administration of MBαvβ3 or control MB-KnottinScrambled. After in vivo blocking of integrin receptors, the imaging signal after the administration of MB-KnottinIntegrin decreased significantly (by 64%). The imaging signals after the administration of MB-KnottinIntegrin were not significantly different in the groups of tumor-bearing mice imaged with MB-KnottinIntegrin and with MBcRGD. Ex vivo immunofluorescence confirmed integrin expression on endothelial cells of human ovarian adenocarcinoma xenograft tumors. Conclusion: Integrin-binding knottin peptides can be conjugated to the surface of microbubbles and used for in vivo targeted contrast-enhanced ultrasound imaging of tumor angiogenesis. Our results demonstrate that microbubbles conjugated to small peptide-targeting ligands provide imaging signals higher than those provided by a large antibody molecule.

  • targeted ultrasound imaging
  • contrast-enhanced ultrasound imaging
  • ovarian cancer
  • knottin peptides

Footnotes

  • COPYRIGHT © 2010 by the Society of Nuclear Medicine, Inc.

View Full Text
PreviousNext
Back to top

In this issue

Journal of Nuclear Medicine: 51 (3)
Journal of Nuclear Medicine
Vol. 51, Issue 3
March 2010
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
Print
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for your interest in spreading the word on Journal of Nuclear Medicine.

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Targeted Contrast-Enhanced Ultrasound Imaging of Tumor Angiogenesis with Contrast Microbubbles Conjugated to Integrin-Binding Knottin Peptides
(Your Name) has sent you a message from Journal of Nuclear Medicine
(Your Name) thought you would like to see the Journal of Nuclear Medicine web site.
Citation Tools
Targeted Contrast-Enhanced Ultrasound Imaging of Tumor Angiogenesis with Contrast Microbubbles Conjugated to Integrin-Binding Knottin Peptides
Jürgen K. Willmann, Richard H. Kimura, Nirupama Deshpande, Amelie M. Lutz, Jennifer R. Cochran, Sanjiv S. Gambhir
Journal of Nuclear Medicine Mar 2010, 51 (3) 433-440; DOI: 10.2967/jnumed.109.068007

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
Share
Targeted Contrast-Enhanced Ultrasound Imaging of Tumor Angiogenesis with Contrast Microbubbles Conjugated to Integrin-Binding Knottin Peptides
Jürgen K. Willmann, Richard H. Kimura, Nirupama Deshpande, Amelie M. Lutz, Jennifer R. Cochran, Sanjiv S. Gambhir
Journal of Nuclear Medicine Mar 2010, 51 (3) 433-440; DOI: 10.2967/jnumed.109.068007
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One
Bookmark this article

Jump to section

  • Article
    • Abstract
    • MATERIALS AND METHODS
    • RESULTS
    • DISCUSSION
    • CONCLUSION
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • PDF

Related Articles

  • This Month in JNM
  • PubMed
  • Google Scholar

Cited By...

  • Efficacy of Affibody-Based Ultrasound Molecular Imaging of Vascular B7-H3 for Breast Cancer Detection
  • Thy1-Targeted Microbubbles for Ultrasound Molecular Imaging of Pancreatic Ductal Adenocarcinoma
  • Molecular Imaging of Ovarian Cancer
  • Protein Engineering for Cardiovascular Therapeutics: Untapped Potential for Cardiac Repair
  • Metastatic Biomarker Discovery Through Proteomics
  • Volumetric Contrast-Enhanced Ultrasound Imaging to Assess Early Response to Apoptosis-Inducing Anti-Death Receptor 5 Antibody Therapy in a Breast Cancer Animal Model
  • Impact of Screening Test Performance and Cost on Mortality Reduction and Cost-effectiveness of Multimodal Ovarian Cancer Screening
  • Evaluation of Tumor Angiogenesis in a Mouse PC-3 Prostate Cancer Model Using Dynamic Contrast-Enhanced Sonography
  • Ultrasound Microbubbles for Molecular Diagnosis, Therapy, and Theranostics
  • A Triple-Targeted Ultrasound Contrast Agent Provides Improved Localization to Tumor Vasculature
  • Google Scholar

More in this TOC Section

  • 11C-Methionine PET of Myocardial Inflammation in a Rat Model of Experimental Autoimmune Myocarditis
  • Counting Rate Characteristics and Image Distortion in Preclinical PET Imaging During Radiopharmaceutical Therapy
  • Design and Fabrication of Kidney Phantoms for Internal Radiation Dosimetry Using 3D Printing Technology
Show more Basic Science Investigations

Similar Articles

SNMMI

© 2022 Journal of Nuclear Medicine

Powered by HighWire