Ultrasound contrast microbubbles targeted to tumor angiogenesis specifically bind tumor-derived endothelial cells

Gregory E. Weller, F. S. Villanueva, M. K.K. Wong, R. A. Modzelewski, A. L. Klibanov, W. R. Wagner

Research output: Contribution to journalConference article

Abstract

Angiogenesis is a key phenomenon in the continued growth of clinically-significant tumors. Endothelial cells (ECs) of tumor vasculature are phenotypically dissimilar from those in normal tissues, and are characterized by altered expression of molecular markers on the EC surface. Various peptides have been identified that specifically bind to tumor angiogenic endothelium, including the tripeptide Arg-Arg-Leu (MW3). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) can be specifically targeted to EC inflammatory markers. Here, we hypothesized that MBs targeted via MW3 would specifically adhere to tumor angiogenic ECs in vitro. Microbubbles were conjugated via avidin/biotin bridging chemistry to cyclic peptides containing either MW3 or glycine control tripeptides. In a parallel plate chamber, MBs were perfused across coverslips of cultured human coronary artery ECs (HCAECs) or mouse tumor-derived ECs (TDECs) (3 min; wall shear rate 100s-1) and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip. MW3-MB adherence was 3 to 6-fold greater than glycine-MB (p<0.01). MW3-MB adherence to TDECs was 3 times greater than to HCAECs (p<0.01). These data demonstrate that MW3-MBs specifically adhere to tumor angiogenic ECs in vitro, potentially offering a means for noninvasive functional imaging of tumor neovascularization and therapeutic tumor targeting.

Original languageEnglish (US)
Pages (from-to)897-898
Number of pages2
JournalAnnual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
Volume2
StatePublished - Dec 1 2002
EventProceedings of the 2002 IEEE Engineering in Medicine and Biology 24th Annual Conference and the 2002 Fall Meeting of the Biomedical Engineering Society (BMES / EMBS) - Houston, TX, United States
Duration: Oct 23 2002Oct 26 2002

Fingerprint

Microbubbles
Endothelial cells
Tumors
Endothelial Cells
Ultrasonics
Neoplasms
arginyl-arginyl-leucine
Glycine
Amino acids
Coronary Vessels
Cyclic Peptides
Avidin
Biotin
Shear deformation
Lipids
Peptides
Endothelium
Adhesion
Tissue
Imaging techniques

All Science Journal Classification (ASJC) codes

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

Cite this

@article{792e876331eb4dbbb23ee68185d94288,
title = "Ultrasound contrast microbubbles targeted to tumor angiogenesis specifically bind tumor-derived endothelial cells",
abstract = "Angiogenesis is a key phenomenon in the continued growth of clinically-significant tumors. Endothelial cells (ECs) of tumor vasculature are phenotypically dissimilar from those in normal tissues, and are characterized by altered expression of molecular markers on the EC surface. Various peptides have been identified that specifically bind to tumor angiogenic endothelium, including the tripeptide Arg-Arg-Leu (MW3). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) can be specifically targeted to EC inflammatory markers. Here, we hypothesized that MBs targeted via MW3 would specifically adhere to tumor angiogenic ECs in vitro. Microbubbles were conjugated via avidin/biotin bridging chemistry to cyclic peptides containing either MW3 or glycine control tripeptides. In a parallel plate chamber, MBs were perfused across coverslips of cultured human coronary artery ECs (HCAECs) or mouse tumor-derived ECs (TDECs) (3 min; wall shear rate 100s-1) and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip. MW3-MB adherence was 3 to 6-fold greater than glycine-MB (p<0.01). MW3-MB adherence to TDECs was 3 times greater than to HCAECs (p<0.01). These data demonstrate that MW3-MBs specifically adhere to tumor angiogenic ECs in vitro, potentially offering a means for noninvasive functional imaging of tumor neovascularization and therapeutic tumor targeting.",
author = "Weller, {Gregory E.} and Villanueva, {F. S.} and Wong, {M. K.K.} and Modzelewski, {R. A.} and Klibanov, {A. L.} and Wagner, {W. R.}",
year = "2002",
month = "12",
day = "1",
language = "English (US)",
volume = "2",
pages = "897--898",
journal = "Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings",
issn = "1557-170X",
publisher = "Institute of Electrical and Electronics Engineers Inc.",

}

Ultrasound contrast microbubbles targeted to tumor angiogenesis specifically bind tumor-derived endothelial cells. / Weller, Gregory E.; Villanueva, F. S.; Wong, M. K.K.; Modzelewski, R. A.; Klibanov, A. L.; Wagner, W. R.

In: Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings, Vol. 2, 01.12.2002, p. 897-898.

Research output: Contribution to journalConference article

TY - JOUR

T1 - Ultrasound contrast microbubbles targeted to tumor angiogenesis specifically bind tumor-derived endothelial cells

AU - Weller, Gregory E.

AU - Villanueva, F. S.

AU - Wong, M. K.K.

AU - Modzelewski, R. A.

AU - Klibanov, A. L.

AU - Wagner, W. R.

PY - 2002/12/1

Y1 - 2002/12/1

N2 - Angiogenesis is a key phenomenon in the continued growth of clinically-significant tumors. Endothelial cells (ECs) of tumor vasculature are phenotypically dissimilar from those in normal tissues, and are characterized by altered expression of molecular markers on the EC surface. Various peptides have been identified that specifically bind to tumor angiogenic endothelium, including the tripeptide Arg-Arg-Leu (MW3). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) can be specifically targeted to EC inflammatory markers. Here, we hypothesized that MBs targeted via MW3 would specifically adhere to tumor angiogenic ECs in vitro. Microbubbles were conjugated via avidin/biotin bridging chemistry to cyclic peptides containing either MW3 or glycine control tripeptides. In a parallel plate chamber, MBs were perfused across coverslips of cultured human coronary artery ECs (HCAECs) or mouse tumor-derived ECs (TDECs) (3 min; wall shear rate 100s-1) and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip. MW3-MB adherence was 3 to 6-fold greater than glycine-MB (p<0.01). MW3-MB adherence to TDECs was 3 times greater than to HCAECs (p<0.01). These data demonstrate that MW3-MBs specifically adhere to tumor angiogenic ECs in vitro, potentially offering a means for noninvasive functional imaging of tumor neovascularization and therapeutic tumor targeting.

AB - Angiogenesis is a key phenomenon in the continued growth of clinically-significant tumors. Endothelial cells (ECs) of tumor vasculature are phenotypically dissimilar from those in normal tissues, and are characterized by altered expression of molecular markers on the EC surface. Various peptides have been identified that specifically bind to tumor angiogenic endothelium, including the tripeptide Arg-Arg-Leu (MW3). Previously, we have shown that lipid-based ultrasound contrast microbubbles (MBs) can be specifically targeted to EC inflammatory markers. Here, we hypothesized that MBs targeted via MW3 would specifically adhere to tumor angiogenic ECs in vitro. Microbubbles were conjugated via avidin/biotin bridging chemistry to cyclic peptides containing either MW3 or glycine control tripeptides. In a parallel plate chamber, MBs were perfused across coverslips of cultured human coronary artery ECs (HCAECs) or mouse tumor-derived ECs (TDECs) (3 min; wall shear rate 100s-1) and washed. Adhesion to ECs was quantified in 20 random microscopic fields per coverslip. MW3-MB adherence was 3 to 6-fold greater than glycine-MB (p<0.01). MW3-MB adherence to TDECs was 3 times greater than to HCAECs (p<0.01). These data demonstrate that MW3-MBs specifically adhere to tumor angiogenic ECs in vitro, potentially offering a means for noninvasive functional imaging of tumor neovascularization and therapeutic tumor targeting.

UR - http://www.scopus.com/inward/record.url?scp=0036916797&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0036916797&partnerID=8YFLogxK

M3 - Conference article

AN - SCOPUS:0036916797

VL - 2

SP - 897

EP - 898

JO - Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings

JF - Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings

SN - 1557-170X

ER -