Project #3 is developed to address the critical needs of novel molecular imaging approaches for early detection of breast cancer. We have identified a moleculer target, urokinase plasminogen activator receptor (uPAR) for receptor targeted MR imaging of breast cancer. uPAR is highly expressed in human breast cancer cells at levels of 14,000 to 500,000 uPAR/cell relative to 2,500/cell in normal mammary epithelial cells. An increased level of uPAR is considered to be associated with tumor aggressiveness, the presence of distant metastasis and poor prognosis. Previous studies have shown that the amino terminal fragment (ATF) peptide of uPAR is responsible for recognition and specific binding to the tumor cell. We propose to develop a uPAR-targeted paramagnetic iron oxide (IO) nanoparticle imaging probe for molecular Magnetic Resolnance Imaging (MRI) of breast cancer. This imaging strategy takes advantages of our experience and ability to produce the ATF in large quantity, our technology of formulating and synethsizing IO nanoparticles for optimal MRI contrast via T2- shortening effect and the chemistry of functionalizing particle surface for conjugating tumor targeting peptides. Given the capability of uPAR targeting with the ATF peptide and strong MRI contrast induced by IO nanoparticles, we hypothesize that this receptor-targeted MRI probe may lead to the accumulation of ATF conjugated IO nanoparticles in the tumor, producing sufficient contrast to detect tumors with elevated level of uPAR. Our preliminary data demonstrated that this breast cancer targeted molecular MRI can be achieved in a mouse mammary tumor model.
Specific aims of this project are: 1) to optimize the method for conjugating the ATF peptide to IO nanoparticles and to examine the specificity of the uPAR targeted-imaging probe in normal and breast cancer cells in vitro; 2) to investigate the specificity and sensitivity of uPAR targeted ATF-IO nanoparticles in detection of breast cancer using mouse mammary tumor, human tumor xenograft, and transgenic tumor models; 3) to examine the biodistribution and toxicity of ATF-IO nanoparticles;and 4) to characterize MRI contrast properties of ATF-IO nanoparticles and to develop imaging methods appropriate for imaging of receptor targeted IO nanoprobes in vivo. It is anticipated that this tumor receptor-targeted MRI probe and imaging method can improve the specificity of breast cancer imaging be translated to clinical applications in the future.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA128301-05
Application #
8382624
Study Section
Special Emphasis Panel (ZCA1-SRRB-9)
Project Start
Project End
2014-08-31
Budget Start
2012-09-01
Budget End
2013-08-31
Support Year
5
Fiscal Year
2012
Total Cost
$155,585
Indirect Cost
$54,780
Name
Emory University
Department
Type
DUNS #
066469933
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Tian, Zhiqiang; Liu, Lizhi; Zhang, Zhenfeng et al. (2017) A supervoxel-based segmentation method for prostate MR images. Med Phys 44:558-569
Liu, Lizhi; Tian, Zhiqiang; Zhang, Zhenfeng et al. (2016) Computer-aided Detection of Prostate Cancer with MRI: Technology and Applications. Acad Radiol 23:1024-46
Orza, Anamaria; Yang, Yi; Feng, Ting et al. (2016) A nanocomposite of Au-AgI core/shell dimer as a dual-modality contrast agent for x-ray computed tomography and photoacoustic imaging. Med Phys 43:589
Pike, Robert; Lu, Guolan; Wang, Dongsheng et al. (2016) A Minimum Spanning Forest-Based Method for Noninvasive Cancer Detection With Hyperspectral Imaging. IEEE Trans Biomed Eng 63:653-63
Tian, Zhiqiang; Liu, Lizhi; Zhang, Zhenfeng et al. (2016) Superpixel-Based Segmentation for 3D Prostate MR Images. IEEE Trans Med Imaging 35:791-801
Schuster, David M; Nanni, Cristina; Fanti, Stefano (2016) PET Tracers Beyond FDG in Prostate Cancer. Semin Nucl Med 46:507-521
Dance, David R; Sechopoulos, Ioannis (2016) Dosimetry in x-ray-based breast imaging. Phys Med Biol 61:R271-R304
Odewole, Oluwaseun A; Oyenuga, Oyeladun A; Tade, Funmilayo et al. (2015) Reproducibility and reliability of anti-3-[ยน?F]FACBC uptake measurements in background structures and malignant lesions on follow-up PET-CT in prostate carcinoma: an exploratory analysis. Mol Imaging Biol 17:277-83
Pike, Robert; Sechopoulos, Ioannis; Fei, Baowei (2015) A minimum spanning forest based classification method for dedicated breast CT images. Med Phys 42:6190-202
Qin, Xulei; Wang, Silun; Shen, Ming et al. (2015) Register cardiac fiber orientations from 3D DTI volume to 2D ultrasound image of rat hearts. Proc SPIE Int Soc Opt Eng 9415:

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