Paramagnetic chemical exchange saturation transfer (PARACEST) agents offer a potential new paradigm in MR imaging. An advantage to this class of agents is the ability to switch each agent on or off through selective RF irradiation applied at the frequency of either its bound water resonance or an exchanging NH group. In their "off" state, i.e. when not specifically irradiated, PARACEST agents will not interfere with conventional MR imaging sequences, with or without gadolinium. In principle, PARACEST agents can be tailored to each application because their effects depend on their water exchange rates, and these rates can be modified using rational chemical principles. This feature also makes them an attractive platform for the development of responsive agents. The goal of this BRP is to realize the full potential of these compounds as contrast agents in vivo, by systematically addressing a number of basic, theoretical and practical questions. These include establishing the relationships among the magnitude of the effect measured in an imaging experiment and the water exchange lifetime, the magnitude of the chemical shift difference between the bound and bulk water, the strength of the saturating RF field, SAR, concentration, and local environment in vivo. This partnership is made up of two academic institutions and an industrial collaborator. The three main overlapping and interactive areas of focus are: lanthanide chemistry, which will be carried out at UT Dallas (UTD);Pulse sequence implementation, theory, simulations and in vitro validation which will be carried out primarily at the General Electric Global Research Center (GEGRC) and in vivo validation carried out primarily at the BIDMC. Dean Sherry (Project Leader, UTD) is an internationally recognized expert in the synthesis and characterization of lanthanide chelates and has expertise in basic NMR exchange theory. Thomas Dixon and Ileana Hancu (Project Leaders, GEGRC) are both experts in NMR and MR imaging. Robert Lenkinski (PI, BIDMC) is an NMR spectroscopist with expertise both in lanthanide agents and MR imaging. David Alsop (Lead Investigator, BIDMC) has a long track record in optimizing Arterial Spin Labeling perfusion studies, where the detection of small signal intensity changes in the presence of RF irradiation is necessary. Over the past several years, this team has been collaborating on the theoretical and practical aspects of the PARACEST effect. The successful completion of this project will result in three agents (intravascular, pH, and Redox responsive) and MR acquisition strategies for use in human studies.

Public Health Relevance

Paramagnetic chemical exchange saturation transfer (PARACEST) agents offer a potential new paradigm in MR imaging. The goal of this BRP is to realize the full potential of these compounds as contrast agents in vivo, by systematically addressing a number of basic, theoretical and practical questions. The successful completion of this project will result in three agents (intravascular, pH, and Redox responsive) and MR acquisition strategies for use in human studies.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB004582-08
Application #
8651911
Study Section
Special Emphasis Panel (ZRG1-SBIB-U (51))
Program Officer
Liu, Christina
Project Start
2005-01-01
Project End
2015-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
8
Fiscal Year
2014
Total Cost
$845,512
Indirect Cost
$141,129
Name
University of Texas Sw Medical Center Dallas
Department
Radiation-Diagnostic/Oncology
Type
Schools of Medicine
DUNS #
800771545
City
Dallas
State
TX
Country
United States
Zip Code
75390
Evbuomwan, Osasere M; Lee, Joohwan; Woods, Mark et al. (2014) The presence of fast-exchanging proton species in aqueous solutions of paraCEST agents can impact rate constants measured for slower exchanging species when fitting CEST spectra to the Bloch equations. Inorg Chem 53:10012-4
Lin, Chien-Yuan; Yadav, Nirbhay N; Ratnakar, James et al. (2014) In vivo imaging of paraCEST agents using frequency labeled exchange transfer MRI. Magn Reson Med 71:286-93
Do, Quyen N; Ratnakar, James S; Kovács, Zoltán et al. (2014) Redox- and hypoxia-responsive MRI contrast agents. ChemMedChem 9:1116-29
Mani, Tomoyasu; Opina, Ana Christina L; Zhao, Piyu et al. (2014) The stereochemistry of amide side chains containing carboxyl groups influences water exchange rates in EuDOTA-tetraamide complexes. J Biol Inorg Chem 19:161-71
Song, Bo; Wu, Yunkou; Yu, Mengxiao et al. (2013) A europium(III)-based PARACEST agent for sensing singlet oxygen by MRI. Dalton Trans 42:8066-9
Vinogradov, Elena; Sherry, A Dean; Lenkinski, Robert E (2013) CEST: from basic principles to applications, challenges and opportunities. J Magn Reson 229:155-72
Zhang, Shanrong; Zhou, Kejin; Huang, Gang et al. (2013) A novel class of polymeric pH-responsive MRI CEST agents. Chem Commun (Camb) 49:6418-20
Ratnakar, S James; Soesbe, Todd C; Lumata, Lloyd Laporca et al. (2013) Modulation of CEST images in vivo by T1 relaxation: a new approach in the design of responsive PARACEST agents. J Am Chem Soc 135:14904-7
Evbuomwan, Osasere M; Merritt, Matthew E; Kiefer, Garry E et al. (2012) Nanoparticle-based PARACEST agents: the quenching effect of silica nanoparticles on the CEST signal from surface-conjugated chelates. Contrast Media Mol Imaging 7:19-25
Vinogradov, Elena; Soesbe, Todd C; Balschi, James A et al. (2012) pCEST: Positive contrast using Chemical Exchange Saturation Transfer. J Magn Reson 215:64-73

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