The main objective of this project is to develop a contrast agent to allow noninvasive imaging and monitoring of breast cancer with molecular specificity. The basis of the proposed method is a combination of optoacoustic imaging, nanotechnology and molecular biology of cancer. Laser Optoacoustic Imaging System (LOIS) uses near-infrared laser pulses to generate acoustic sources in tumors and the time-resolved detection of resulting transient ultrasonic waves. Clinical studies on breast cancer patients demonstrated that the combination of pulsed laser excitation (which provides high optical contrast between normal and malignant tissue) with the time-resolved detection of ultrasonic waves (which provides undistorted tomographic information from significant depths of tissue), yields a breast imaging system with capability to detect small tumors in situ. On the other hand, one can predict that some breast tumors may possess materially reduced optoacoustic contrast relative to that currently observed in patients with advanced cancer. These cases include: (1) early cancer stages (tumors with dimensions of 1-3 mm) that do not possess dense microvascular network, and (2) tumors treated with anti-angiogenesis chemotherapy. Therefore, we propose to develop and test a Nanoparticulate Optoacoustic Contrast Agent (NOCA) based on gold nanorods (NR) conjugated to antibodies against breast cancer receptors. Recently we demonstrated that gold nanorods represent a unique optoacoustic contrast agent. The optical absorption in gold nanorods is over 10(8)1/cm, i.e. >1000 times stronger than that of any organic molecules. Average near-IR absorption of cancerous tissue loaded with nanorods in concentration of only 10 nanorods per cell will provide additional noticeable contrast of delta-mu about 0.5 cm(-1) relative to normal tissue. Furthermore, the laser-induced acoustic signal from gold nanorods was found an order of magnitude stronger than an optoacoustic signal from dye-solution with equal absorbance. We propose to develop NOCA to utilize the full diagnostic power of LOIS, expanding its imaging capabilities to early carcinoma in situ and other breast tumors with underdeveloped microvasculature. The Phase-I project should result in the proof of feasibility in animals with simultaneous demonstration of our capability to control bioeffects of laser - nanorod interactions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Business Innovation Research Grants (SBIR) - Phase II (R44)
Project #
7R44CA110137-06
Application #
8486776
Study Section
Special Emphasis Panel (ZRG1-SBIB-H (13))
Program Officer
Narayanan, Deepa
Project Start
2005-09-01
Project End
2014-04-30
Budget Start
2012-11-06
Budget End
2014-04-30
Support Year
6
Fiscal Year
2009
Total Cost
$268,705
Indirect Cost
Name
Tomowave Laboratories, Inc.
Department
Type
DUNS #
962126616
City
Houston
State
TX
Country
United States
Zip Code
77081
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Liopo, Anton V; Conjusteau, André; Chumakova, Olga V et al. (2012) Highly purified biocompatible gold nanorods for contrasted optoacoustic imaging of small animal models. Nanosci Nanotechnol Lett 4:681-686
Liopo, Anton V; Conjusteau, André; Konopleva, Marina et al. (2012) Laser nanothermolysis of human leukemia cells using functionalized plasmonic nanoparticles. Nano Biomed Eng 4:66-75
Wang, Kun; Ermilov, Sergey A; Su, Richard et al. (2011) An imaging model incorporating ultrasonic transducer properties for three-dimensional optoacoustic tomography. IEEE Trans Med Imaging 30:203-14
Lamela, Horacio; Gallego, Daniel; Gutierrez, Rebeca et al. (2011) Interferometric fiber optic sensors for biomedical applications of optoacoustic imaging. J Biophotonics 4:184-92

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