Breast-conserving surgery, or lumpectomy, is the most common surgical procedure for patients diagnosed with an early stage of invasive breast cancer. Clearly defined tumor margins and complete surgical removal of tumors are critical for preventing local recurrence and increasing disease-free survival. Currently, there is no accurate method to identify tumor margins pre- or intra-operatively. About 20% to 30% of the patients who undergo lumpectomy require additional surgery to excise any remaining tumors due to the presence of positive tumor margins. To develop a sensitive approach for detecting tumor margins in breast tissues, we propose to engineer a tumor targeted nanoparticle imaging probe by labeling a peptide containing the receptor binding domain (ATF) of urokinase plasminogen activator (uPA) with a near infrared (NIR) dye and then conjugating these complexes to a magnetic iron oxide (IO) nanoparticle. The objectives of this proposed study are: 1) to develop new NIR optical imaging nanoprobes targeting the cellular receptor for uPA;2) to develop a sensitive fluorescence tomography system for imaging-guided surgery aimed at completely removing tumor lesions within breast tissue;and 3) to examine the effect of the optical imaging guided resection of mammary tumors on local tumor recurrence and metastasis in a mouse mammary tumor model. The development of novel tumor targeted NIR imaging nanoprobes, in combination with a sensitive and high resolution NIR fluorescence tomography system, should have great potential for determining tumor margins during surgery, preventing tumor recurrence and therefore, increasing the survival rate of breast cancer patients.

Public Health Relevance

The objective of this proposed study is to develop a novel optical imaging approach that combines tumor targeted optical imaging probes with advanced optical imaging instrumentation for the detection of breast cancer and for outlining the tumor border during breast conserving surgery. In this study, we will develop urokinase plasminogen activator receptor (uPAR) targeted near infrared (NIR) dye-labeled nanoparticles to deliver the imaging probes into breast tumors, the location and depth of the tumors will be detected using 3D diffuse fluorescence tomography. Success in this proposed study should provide us with novel optical imaging agents as well as instruments to address the urgent need for preventing tumor recurrence after breast conserving surgery and ultimately, to improve the survival rate of breast cancer patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA133722-04
Application #
8062055
Study Section
Special Emphasis Panel (ZRG1-NANO-M (01))
Program Officer
Nordstrom, Robert J
Project Start
2008-04-25
Project End
2013-01-31
Budget Start
2011-02-01
Budget End
2012-01-31
Support Year
4
Fiscal Year
2011
Total Cost
$309,239
Indirect Cost
Name
Emory University
Department
Surgery
Type
Schools of Medicine
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Yang, Emmy; Qian, Weiping; Cao, Zehong et al. (2015) Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery. Theranostics 5:43-61
Satpathy, Minati; Zielinski, Rafal; Lyakhov, Ilya et al. (2015) Optical imaging of ovarian cancer using HER-2 affibody conjugated nanoparticles. Methods Mol Biol 1219:171-85
Satpathy, Minati; Wang, Liya; Zielinski, Rafal et al. (2014) Active targeting using HER-2-affibody-conjugated nanoparticles enabled sensitive and specific imaging of orthotopic HER-2 positive ovarian tumors. Small 10:544-55
Xi, Lei; Satpathy, Minati; Zhao, Qing et al. (2014) HER-2/neu targeted delivery of a nanoprobe enables dual photoacoustic and fluorescence tomography of ovarian cancer. Nanomedicine 10:669-77
Xi, Lei; Grobmyer, Stephen R; Zhou, Guangyin et al. (2014) Molecular photoacoustic tomography of breast cancer using receptor targeted magnetic iron oxide nanoparticles as contrast agents. J Biophotonics 7:401-9
Xi, Lei; Zhou, Guangyin; Gao, Ning et al. (2014) Photoacoustic and fluorescence image-guided surgery using a multifunctional targeted nanoprobe. Ann Surg Oncol 21:1602-9
Yang, Lily; Sajja, Hari Krishna; Cao, Zehong et al. (2013) uPAR-targeted optical imaging contrasts as theranostic agents for tumor margin detection. Theranostics 4:106-18
Zhou, Zhengyang; Chen, Hongwei; Lipowska, Malgorzata et al. (2013) A dual-modal magnetic nanoparticle probe for preoperative and intraoperative mapping of sentinel lymph nodes by magnetic resonance and near infrared fluorescence imaging. J Biomater Appl 28:100-11
Tan, Yiyong; Cao, Zehong; Sajja, Hari Krishna et al. (2013) DOT corrected fluorescence molecular tomography using targeted contrast agents for small animal tumor imaging. J Xray Sci Technol 21:43-52
Qian, Ximei; Emory, Steven R; Nie, Shuming (2012) Anchoring molecular chromophores to colloidal gold nanocrystals: surface-enhanced Raman evidence for strong electronic coupling and irreversible structural locking. J Am Chem Soc 134:2000-3

Showing the most recent 10 out of 16 publications