Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy

Anna G. Sorace, Reshu Saini, Marshall Mahoney, Kenneth Hoyt

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.

Original languageEnglish (US)
Pages (from-to)1543-1550
Number of pages8
JournalJournal of Ultrasound in Medicine
Volume31
Issue number10
StatePublished - Oct 1 2012

Fingerprint

Molecular Imaging
Contrast Media
Ultrasonography
Microbubbles
Neoplasms
Therapeutics
Group Psychotherapy
Vascular Endothelial Growth Factor Receptor-2
Control Groups
P-Selectin
Neoplasm Staging
Microvessels
Integrins
Necrosis
Drug Therapy
Injections
Antibodies

Keywords

  • Angiogenesis
  • Antiangiogenic therapy
  • Contrast-enhanced ultrasound
  • Microbubbles
  • Targeted contrast agent

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy. / Sorace, Anna G.; Saini, Reshu; Mahoney, Marshall; Hoyt, Kenneth.

In: Journal of Ultrasound in Medicine, Vol. 31, No. 10, 01.10.2012, p. 1543-1550.

Research output: Contribution to journalArticle

@article{cc8048e788d04df4be42944f6ed2325a,
title = "Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy",
abstract = "Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8{\%} change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4{\%} decrease in tumor vascularity, whereas the control group had a 56.4{\%} increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.",
keywords = "Angiogenesis, Antiangiogenic therapy, Contrast-enhanced ultrasound, Microbubbles, Targeted contrast agent",
author = "Sorace, {Anna G.} and Reshu Saini and Marshall Mahoney and Kenneth Hoyt",
year = "2012",
month = "10",
day = "1",
language = "English (US)",
volume = "31",
pages = "1543--1550",
journal = "Journal of Ultrasound in Medicine",
issn = "0278-4297",
publisher = "American Institute of Ultrasound in Medicine",
number = "10",

}

TY - JOUR

T1 - Molecular ultrasound imaging using a targeted contrast agent for assessing early tumor response to antiangiogenic therapy

AU - Sorace, Anna G.

AU - Saini, Reshu

AU - Mahoney, Marshall

AU - Hoyt, Kenneth

PY - 2012/10/1

Y1 - 2012/10/1

N2 - Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.

AB - Objectives-Contrast-enhanced ultrasound (US) and targeted microbubbles have been shown to be advantageous for angiogenesis evaluation and disease staging in cancer. This study explored molecular US imaging of a multitargeted microbubble for assessing the early tumor response to antiangiogenic therapy. Methods-Targetreceptor expression of2LMPbreast cancer cellswasquantified by flow cytometric analysisandcharacterization established with antibodies againstmouseαVβ3- integrin, P-selectin, and vascular endothelial growth factor receptor 2. Tumor-bearing mice (n = 15 per group) underwent contrast-enhanced US imaging of multitargeted microbubbles. Microbubble accumulation was calculated by destruction-replenishment techniquesandtime-intensity curve analysis. On day 0, mice underwent baseline imaging. Next, therapy group mice were injected with a 0.2-mg dose of bevacizumab, and controls received matched saline injections. Imaging was repeated on days 1 and 3. After imaging was completed on day 3, the mice were euthanized and tumors excised. Histologic analysis of microvessel density and intratumoral necrosis was completed on tumor sections. Results-Onday 3 after bevacizumab dosing, a 71.8% change in tumor vasculaturewas shown between the therapy and control groups (P = .01). The therapy group had a 15.4% decrease in tumor vascularity, whereas the control group had a 56.4% increase. Conclusions- MolecularUSimaging of angiogenic markers can detect the early tumor response to drug therapy.

KW - Angiogenesis

KW - Antiangiogenic therapy

KW - Contrast-enhanced ultrasound

KW - Microbubbles

KW - Targeted contrast agent

UR - http://www.scopus.com/inward/record.url?scp=84867221880&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84867221880&partnerID=8YFLogxK

M3 - Article

C2 - 23011617

AN - SCOPUS:84867221880

VL - 31

SP - 1543

EP - 1550

JO - Journal of Ultrasound in Medicine

JF - Journal of Ultrasound in Medicine

SN - 0278-4297

IS - 10

ER -