This proposal has a technology development component and a basic immunobiological component. It consists of three Specific Aims: (1) development of novel intracellular MRI agents and associated cell labeling protocols, and measurement of the cell labeling efficiency and lifetime; (2) biological characterizations via quantitative cytotoxicity, proliferation, and immunological assays of labeled immune cells, such as dendritic cells (DCs) and macrophages; and (3) in vivo studies where labeled immune cells will be injected into NOD mice and imaged using extremely-high field (11.7 T) MRI. We will visualize the biodistribution of the labeled cells following intravenous inoculation and the time-lapse cell migration following focal injection into specific tissue sites. We will test the hypothesis that different subsets of DCs have different migratory patterns in vivo based on their maturation state. Using the NOD mouse we will test the hypothesis that the ability of mature DCs to prevent diabetes is dependent, in part, on their migratory capacity. A long-term application of this technology is monitoring the trafficking of cellular therapeutics in vivo. The proposed research project is highly interdisciplinary, and we have assembled a diverse team of investigators in the Pittsburgh area with expertise in in vivo magnetic resonance microscopy (Ahrens), immunology (Morel) and biological reagent design (Ernst/Waggoner).

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003453-04
Application #
7367810
Study Section
Medical Imaging Study Section (MEDI)
Program Officer
Zhang, Yantian
Project Start
2005-02-01
Project End
2011-01-31
Budget Start
2008-02-01
Budget End
2011-01-31
Support Year
4
Fiscal Year
2008
Total Cost
$276,653
Indirect Cost
Name
Carnegie-Mellon University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
052184116
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Hitchens, T Kevin; Ye, Qing; Eytan, Danielle F et al. (2011) 19F MRI detection of acute allograft rejection with in vivo perfluorocarbon labeling of immune cells. Magn Reson Med 65:1144-53
Bonetto, Fernando; Srinivas, Mangala; Heerschap, Arend et al. (2011) A novel (19)F agent for detection and quantification of human dendritic cells using magnetic resonance imaging. Int J Cancer 129:365-73
Ahrens, Eric T; Young, Won-Bin; Xu, Hongyan et al. (2011) Rapid quantification of inflammation in tissue samples using perfluorocarbon emulsion and fluorine-19 nuclear magnetic resonance. Biotechniques 50:229-34
Morel, Penelope A; Srinivas, Mangala; Turner, Michael S et al. (2011) Gene expression analysis of dendritic cells that prevent diabetes in NOD mice: analysis of chemokines and costimulatory molecules. J Leukoc Biol 90:539-50
Srinivas, Mangala; Heerschap, Arend; Ahrens, Eric T et al. (2010) (19)F MRI for quantitative in vivo cell tracking. Trends Biotechnol 28:363-70
Kadayakkara, Deepak K; Beatty, Pamela L; Turner, Michael S et al. (2010) Inflammation driven by overexpression of the hypoglycosylated abnormal mucin 1 (MUC1) links inflammatory bowel disease and pancreatitis. Pancreas 39:510-5
Kadayakkara, Deepak K K; Janjic, Jelena M; Pusateri, Lisa K et al. (2010) In vivo observation of intracellular oximetry in perfluorocarbon-labeled glioma cells and chemotherapeutic response in the CNS using fluorine-19 MRI. Magn Reson Med 64:1252-9
Srinivas, Mangala; Turner, Michael S; Janjic, Jelena M et al. (2009) In vivo cytometry of antigen-specific t cells using 19F MRI. Magn Reson Med 62:747-53
Janjic, Jelena M; Ahrens, Eric T (2009) Fluorine-containing nanoemulsions for MRI cell tracking. Wiley Interdiscip Rev Nanomed Nanobiotechnol 1:492-501

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