? Development of new contrast materials is important to expand the diagnostic capabilities of MR at the cellular and molecular level. In particular, providing information on cell migration, trafficking and homing would be useful for the development of cell therapies using stem cells and progenitors. Previous cell tracking studies have employed agents containing iron oxide, gadolinium or other metals to generate contrast by influencing the relaxation time of water protons. The drawbacks of using these agents for cell tracking include the feature that cells are detected as positive or negative spots which can be difficult to distinguish from imaging artifacts and also the uncertainty about long-term metal toxicity in-vivo. Chemical Exchange Saturation Transfer (CEST) agents are a new class of MR agents which to date haven't been used for cell tracking. Contrast is generated with these agents by applying a saturation pulse on the agent's protons which rapid chemical exchange with water transferring the signal loss, with the speed of the exchange producing a saturation of multiple water protons from a single exchangeable site on the CEST agent. We are proposing developing a new class of molecular probes for use in cell tracking, inserting these into cells and monitoring their effectiveness in-vivo. Two different types of biopolymer CEST agents will be tested, poly-peptides consisting of D-amino acids (instead of L) and poly-peptides consisting of l-amino acids but with appropriate N-terminal groups resistant to degradation. The advantage of these agents is that their contrast is saturation frequency dependent, allowing multiple """"""""colors"""""""" of agent, which would be useful for tracking multiple cell populations independently with MRI (as compared with the simple on/off contrast of metal based agents). We are interested in developing four different """"""""colors"""""""" for MR imaging, analogous to the capabilities of optical/fluorescent imaging. We will also optimize the sensitivity and delivery of these agents. We hypothesize that the detection of these agents is possible in-vivo and to achieve this goal we will synthesize a series of these agents, and detect transfected neural stem cells individually in live animals. These contrast agents should prove to be highly sensitive due to the chemical exchange amplification of the contrast. In addition, because these agents are composed exclusively of polypeptides, new delivery/targeting strategies may be employed. ? ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01EB006394-03
Application #
7448639
Study Section
Special Emphasis Panel (ZEB1-OSR-C (M1))
Program Officer
Erim, Zeynep
Project Start
2006-08-01
Project End
2011-07-31
Budget Start
2008-08-01
Budget End
2009-07-31
Support Year
3
Fiscal Year
2008
Total Cost
$124,459
Indirect Cost
Name
Hugo W. Moser Research Institute Kennedy Krieger
Department
Type
DUNS #
155342439
City
Baltimore
State
MD
Country
United States
Zip Code
21205
Airan, Raag D; Bar-Shir, Amnon; Liu, Guanshu et al. (2012) MRI biosensor for protein kinase A encoded by a single synthetic gene. Magn Reson Med 68:1919-23
Liu, Guanshu; Moake, Matthew; Har-el, Yah-el et al. (2012) In vivo multicolor molecular MR imaging using diamagnetic chemical exchange saturation transfer liposomes. Magn Reson Med 67:1106-13
Liu, Guanshu; Liang, Yajie; Bar-Shir, Amnon et al. (2011) Monitoring enzyme activity using a diamagnetic chemical exchange saturation transfer magnetic resonance imaging contrast agent. J Am Chem Soc 133:16326-9
Choi, Jonghoon; Kim, Kyobum; Kim, Taeho et al. (2011) Multimodal imaging of sustained drug release from 3-D poly(propylene fumarate) (PPF) scaffolds. J Control Release 156:239-45
Fatemi, Ali; Wilson, Mary Ann; Phillips, Andre W et al. (2011) In vivo magnetization transfer MRI shows dysmyelination in an ischemic mouse model of periventricular leukomalacia. J Cereb Blood Flow Metab 31:2009-18
Friedman, Joshua I; McMahon, Michael T; Stivers, James T et al. (2010) Indirect detection of labile solute proton spectra via the water signal using frequency-labeled exchange (FLEX) transfer. J Am Chem Soc 132:1813-5
Liu, Guanshu; Gilad, Assaf A; Bulte, Jeff W M et al. (2010) High-throughput screening of chemical exchange saturation transfer MR contrast agents. Contrast Media Mol Imaging 5:162-70
Gilad, Assaf A; van Laarhoven, Hanneke W M; McMahon, Michael T et al. (2009) Feasibility of concurrent dual contrast enhancement using CEST contrast agents and superparamagnetic iron oxide particles. Magn Reson Med 61:970-4
McMahon, Michael T; Gilad, Assaf A; DeLiso, Marco A et al. (2008) New ""multicolor"" polypeptide diamagnetic chemical exchange saturation transfer (DIACEST) contrast agents for MRI. Magn Reson Med 60:803-12
Gilad, Assaf A; Ziv, Keren; McMahon, Michael T et al. (2008) MRI reporter genes. J Nucl Med 49:1905-8

Showing the most recent 10 out of 13 publications