Molecular imaging has successfully been utilized in the recent past as a technology for imaging various aspects of mammalian physiology. However, the information that can be obtained using these non-invasive modalities is limited since it relies on the expression and imaging of single gene markers. While this information is useful, it can be misleading. For example, markers over-expressed in diseases tissues are also expressed in normal tissues in a spatio-temporal manner making interpretation of the results in a diagnostic setting potentially difficult. Several studies have demonstrated a high degree of both sensitivity and specificity for the identification and molecular classification of diseases by measuring the expression of multiple disease-associated changes in gene expression. The simultaneous over-expression of more than one of these gene markers is, therefore, more predictive of the disease state. Until now, molecular imaging was unable to image more than one marker at a time, requiring either different imaging technologies to be utilized simultaneously or requiring different probes with short biological half-lives to be imaged in rapid succession. The goal of the proposed study is to develop an imaging paradigm that will allow the detection and imaging of multiple over-expressed cancer disease targets at the same time. In the experiments proposed here we will attempt to conjugate these domains to each of three different ligands to simultaneously target and image, via enzyme re-construction in situ, three different molecular imaging targets. Application of this imaging paradigm will be conducted in vivo with animals bearing tumors that express either a subset or all of the biomarkers required for trans complementation. The proposed career development plan will offer the candidate protected time to further develop her research skills by learning new laboratory techniques, taking selective didactic coursework, and expanding her knowledge and experience in the practical conduct of experimentation both in the laboratory and in the clinic under the close supervision of experienced sponsors with input from consultants, collaborators, colleagues, and other faculty within the University.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01EB006910-03
Application #
7656635
Study Section
Special Emphasis Panel (ZEB1-OSR-D (M1))
Program Officer
Erim, Zeynep
Project Start
2007-08-13
Project End
2012-07-31
Budget Start
2009-08-01
Budget End
2010-07-31
Support Year
3
Fiscal Year
2009
Total Cost
$97,996
Indirect Cost
Name
Case Western Reserve University
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Broome, Ann-Marie; Ramamurthy, Gopal; Lavik, Kari et al. (2015) Optical imaging of targeted ?-galactosidase in brain tumors to detect EGFR levels. Bioconjug Chem 26:660-8
Meyers, Joseph D; Cheng, Yu; Broome, Ann-Marie et al. (2015) Peptide-Targeted Gold Nanoparticles for Photodynamic Therapy of Brain Cancer. Part Part Syst Charact 32:448-457
Shukla, Sourabh; Wen, Amy M; Ayat, Nadia R et al. (2014) Biodistribution and clearance of a filamentous plant virus in healthy and tumor-bearing mice. Nanomedicine (Lond) 9:221-35
Cheng, Yu; Meyers, Joseph D; Agnes, Richard S et al. (2011) Addressing brain tumors with targeted gold nanoparticles: a new gold standard for hydrophobic drug delivery? Small 7:2301-6
Harth, K C; Broome, A-M; Jacobs, M R et al. (2011) Bacterial clearance of biologic grafts used in hernia repair: an experimental study. Surg Endosc 25:2224-9
Cheng, Yu; Meyers, Joseph D; Broome, Ann-Marie et al. (2011) Deep penetration of a PDT drug into tumors by noncovalent drug-gold nanoparticle conjugates. J Am Chem Soc 133:2583-91
Halaweish, Ihab; Harth, Karem; Broome, Ann-Marie et al. (2010) Novel in vitro model for assessing susceptibility of synthetic hernia repair meshes to Staphylococcus aureus infection using green fluorescent protein-labeled bacteria and modern imaging techniques. Surg Infect (Larchmt) 11:449-54
Sandhu, Gurpreet Singh; Solorio, Luis; Broome, Ann-Marie et al. (2010) Whole animal imaging. Wiley Interdiscip Rev Syst Biol Med 2:398-421
Broome, Ann-Marie; Bhavsar, Nihir; Ramamurthy, Gopalakrishnan et al. (2010) Expanding the utility of beta-galactosidase complementation: piece by piece. Mol Pharm 7:60-74