Many human solid tumors reside in environments with an extracellular pH (pHe) that is both sub-physiologic and lower than surrounding healthy tissue. Recent studies have shown that this low pH microenvironment can stimulate in vitro invasion and in vivo metastases. This has led to a great deal of interest in the development of non-invasive imaging strategies for measuring pH in vivo. The overall goal of this proposal is to develop a pH- responsive MR contrast agent that specifically accumulates at sites of low pHe. We hypothesize that this imaging technology will allow for the sensitive detection of 'hostile'microenvironments and will provide an important advance in the specific identification of malignant lesions.
The specific aims for this proposal are (1) to synthesize pH-responsive superparamagnetic iron oxide (SPIO) nanoparticles with various physical and magnetic properties;(2) to characterize the pH-dependent uptake of pH-responsive SPIO in breast cancer cells;and (3) to quantify the size-dependent retention of pH-responsive nanoparticles in tumor xenografts.

Public Health Relevance

We propose to develop a pH-responsive magnetic resonance contrast agent that specifically accumulates at sites of low extracellular pH. We hypothesize that this imaging technology will allow for the sensitive detection of 'hostile'tumor microenvironments and will provide an important advance in the specific identification of malignant lesions.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA140695-02
Application #
7860610
Study Section
Special Emphasis Panel (ZRG1-MEDI-A (09))
Program Officer
Menkens, Anne E
Project Start
2009-06-05
Project End
2011-05-31
Budget Start
2010-06-30
Budget End
2011-05-31
Support Year
2
Fiscal Year
2010
Total Cost
$173,248
Indirect Cost
Name
University of Pennsylvania
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
042250712
City
Philadelphia
State
PA
Country
United States
Zip Code
19104
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Nwe, Kido; Huang, Ching-Hui; Tsourkas, Andrew (2013) Gd-labeled glycol chitosan as a pH-responsive magnetic resonance imaging agent for detecting acidic tumor microenvironments. J Med Chem 56:7862-9
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