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The Molecular Analysis of Breast Cancer Utilizing Targeted Nanoparticle Based Ultrasound Contrast Agents (p. 627-636)

This study was structured to challenge the hypothesis that nano-sized particulates could be molecularly targeted and bound to the prognostic and predictive HER-2/neu cell membrane receptor to elicit detectable changes in ultrasound response from human breast cancer cells. SKBR-3 human breast cancer cells were enlisted to test the efficacy of the particle conjugation strategy used in this study and ultimately, to provide conclusive remarks regarding the validity of the stated hypothesis. A characterization-mode ultrasound (CMUS) system was used to apply a continuum mechanics based, two-step inversion algorithm to reconstruct the mechanical material properties of four cell/agarose test conditions upon three independent test samples. The four test conditions include: Herceptin® conjugated iron oxide nanoparticles bound to cells (HER-con), Herceptin® bound to cells (HER), iso-type matched antibody conjugated iron oxide nanoparticles bound to cells (ISO-con), and Cold Flow Buffer mixed with agarose (CFB). The statistical analysis of these ultrasound results supported the ability to differentiate between HER-2/neu positive SKBR-3 cells that have been successfully tagged with Herceptin® conjugated iron oxide particles to those that have not demonstrated particle binding. These findings serve as promising proof-of-concept data for the development of a quantitative histopathologic evaluation tool directed towards both in situ and in vivo applications. The ultimate goal of this research is to exploit the molecular expression of the HER-2/neu protein to offer rapid, quantitative ultrasound information concerning the malignancy rating of human breast tissue employing tumor targeting nanoparticle based ultrasound contrast agents. When fully developed, this could potentially help 32,000-63,000 women efficiently find their proper treatment strategy to fight and win their battle against breast cancer.

Key words: Breast cancer; HER-2/neu; SKBR-3; Ultrasound; Contrast agent; and Nanoparticle.

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TCRT December 2005

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Volume 4
No. 6 (p 583-712)
December 2005
ISSN 1533-0338

Jason H. Sakamoto, Ph.D.1,2
Bryan R. Smith, M.S.1,2
Bin Xie, M.S.3
Stanislav I. Rokhlin, Ph.D.3
Stephen C. Lee, Ph.D.1,2
Mauro Ferrari, Ph.D.2,4,*

1Biomedical Engineering Center
2Davis Heart and Lung Research Institute
3Nondestructive Evaluation Program
The Ohio State University
Rm. 110A Davis Heart & Lung
Research Lab
473 W. 12th Avenue
Columbus, OH 43210, USA
4The National Cancer Institute
Bethesda, Maryland 20892, USA