An Animal Model Allowing Controlled Receptor Expression for Molecular Ultrasound Imaging

Reshu Saini, Anna G. Sorace, Jason M. Warram, Marshall J. Mahoney, Kurt R. Zinn, Kenneth Hoyt

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Reported in this study is an animal model system for evaluating targeted ultrasound (US) contrast agents binding using adenoviral (Ad) vectors to modulate cellular receptor expression. An Ad vector encoding an extracellular hemagglutinin (HA) epitope tag and a green fluorescent protein (GFP) reporter was used to regulate receptor expression. A low and high receptor density (in breast cancer tumor bearing mice) was achieved by varying the Ad dose with a low plaque forming unit (PFU) on day 1 and high PFU on day 2 of experimentation. Targeted US contrast agents, or microbubbles (MB), were created by conjugating either biotinylated anti-HA or IgG isotype control antibodies to the MB surface with biotin-streptavidin linkage. Targeted and control MBs were administered on both days of experimentation and contrast-enhanced US (CEUS) was performed on each mouse using MB flash destruction technique. Signal intensities from MBs retained within tumor vasculature were analyzed through a custom Matlab program. Results showed intratumoral enhancement attributable to targeted MB accumulation was significantly increased from the low Ad vector dosing and the high Ad vector dosing (p = 0.001). Control MBs showed no significant differences between day 1 and day 2 imaging (p = 0.96). Additionally, targeted MBs showed a 10.5-fold increase in intratumoral image intensity on day 1 and an 18.8-fold increase in image intensity on day 2 compared with their control MB counterparts.

Original languageEnglish (US)
Pages (from-to)172-180
Number of pages9
JournalUltrasound in Medicine and Biology
Volume39
Issue number1
DOIs
StatePublished - Jan 1 2013

Fingerprint

Microbubbles
animal models
Molecular Imaging
Ultrasonography
Animal Models
experimentation
mice
Hemagglutinins
tumors
Contrast Media
biotin
Breast Neoplasms
antibodies
linkages
breast
Streptavidin
destruction
flash
Biotin
Green Fluorescent Proteins

Keywords

  • Adenoviral vectors
  • Contrast-enhanced ultrasound imaging
  • Microbubbles
  • Modulated receptors

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Biophysics
  • Radiology Nuclear Medicine and imaging

Cite this

An Animal Model Allowing Controlled Receptor Expression for Molecular Ultrasound Imaging. / Saini, Reshu; Sorace, Anna G.; Warram, Jason M.; Mahoney, Marshall J.; Zinn, Kurt R.; Hoyt, Kenneth.

In: Ultrasound in Medicine and Biology, Vol. 39, No. 1, 01.01.2013, p. 172-180.

Research output: Contribution to journalArticle

Saini, Reshu ; Sorace, Anna G. ; Warram, Jason M. ; Mahoney, Marshall J. ; Zinn, Kurt R. ; Hoyt, Kenneth. / An Animal Model Allowing Controlled Receptor Expression for Molecular Ultrasound Imaging. In: Ultrasound in Medicine and Biology. 2013 ; Vol. 39, No. 1. pp. 172-180.
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