In recent years, increasing attention has been directed towards the use of B-cell depletion therapy as a treatment option in autoimmune disorders. It appears that the further development of these approaches will depend on a methodology to determine the relation of B-cell depletion to clinical response and how individual patients should be dosed. Thus far, patients have generally been followed by quantification of peripheral blood B cells;however, this measure clearly does not adequately reflect what is happening in the rest of the body. The ability to image B cells in multiple organs in vivo, repeatedly and with good spatial resolution and high sensitivity, would provide an excellent biomarker for this purpose. The overall goal of this proposal is to develop Gd-conjugated dendrimer nanoclusters as B-cell targeted T1 magnetic resonance (MR) imaging contrast agents for the quantification of B cells in lymphoid organs. Using monoclonal antibodies (mAb) to deplete B-cells, we will test these techniques in mice.
Three specific aims are proposed: (1) Synthesize B cell- targeted, Gd-conjugated dendrimer nanoclusters (DNCs) with various physical and magnetic properties;(2) Evaluate the contrast enhancement, circulation time, biodistribution, and elimination of the various DNCs in mice;(3) Evaluate the ability to monitor B-cell depletion in mice.

Public Health Relevance

We propose to develop Gd-conjugated dendrimer nanoclusters as B-cell targeted T1 magnetic resonance (MR) imaging contrast agents for the quantification of B cells in lymphoid organs. MR imaging studies will be used to monitor B cell depletion in the spleen of mice subject to anti-CD20 antibody therapy.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB012065-04
Application #
8523043
Study Section
Clinical Molecular Imaging and Probe Development (CMIP)
Program Officer
Liu, Christina
Project Start
2010-09-15
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$321,968
Indirect Cost
$118,025
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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