The long-range goal of this project is to develop bioactivated magnetic resonance (MR) contrast agents for imaging in vivo process from gene expression to secondary messenger activation. This project is focused on obtaining insights into the interrelated problems of developmental biology and clinical diseases by i. generating MR probes that function as real-time in vivo enzyme reporters, ii. tracking gene expression in whole animals and correlate this information with on going developmental events, and iii. developing biocompatible scaffolds for the efficient delivery of agents in experimental animals, and ultimately humans. It is clear that MR imaging has become one of the most important tools for the diagnosis of a range of clinical problems and in order to maximize the impact of this technique, functional contrast agents must be investigated and developed. Further, the study of developmental biology in whole-animals using a modality that provides temporal resolution, coupled with bioactivated MR contrast agents will result in a deeper understanding of the role of spatial organization with mechanism. Therefore, to create an in vivo MRI assay of enzymatic activities and secondary messengers, MR contrast agents will be designed and synthesized with removable protection groups that largely prevent access of water to a paramagnetic center. By limiting the access of bulk water (q-modulation) the unprocessed agent is designed to be an ineffective contrast agent. Five macrocyclic platforms will be used to generate reversible and irreversible MR reporters of enzymes and secondary messengers that include: sugars, peptides, calcium, phosphorylation. Complexes will be designed, tested and optimized for Beta-galactosidase, Beta-glucoronidase, caspases, MMP's, cathepsin, kinases, and intracellular calcium. We have defined five primary objectives: I. Synthesize and characterize MRI contrast agents with enzyme substrates as water blocking groups of (q-modulation). II. Investigate the relationship between the structure of the agent with observed contrast enhancement, enzyme kinetics, clearance and toxicity. III. Develop intracellular delivery vehicles for MR contrast agents. IV. Synthesize multimodal probes for in vivo validation and co-registration. V. Evaluate the effectiveness of the bioactivated contrast agents in vitro and in vivo.

National Institute of Health (NIH)
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Research Project (R01)
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Metallobiochemistry Study Section (BMT)
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Zhang, Yantian
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Northwestern University at Chicago
Schools of Arts and Sciences
United States
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Rotz, Matthew W; Holbrook, Robert J; MacRenaris, Keith W et al. (2018) A Markedly Improved Synthetic Approach for the Preparation of Multifunctional Au-DNA Nanoparticle Conjugates Modified with Optical and MR Imaging Probes. Bioconjug Chem 29:3544-3549
Rammohan, Nikhil; Holbrook, Robert J; Rotz, Matthew W et al. (2017) Gd(III)-Gold Nanoconjugates Provide Remarkable Cell Labeling for High Field Magnetic Resonance Imaging. Bioconjug Chem 28:153-160
Hung, Andy H; Lilley, Laura M; Hu, Fengqin et al. (2017) Magnetic barcode imaging for contrast agents. Magn Reson Med 77:970-978
Preslar, Adam T; Lilley, Laura M; Sato, Kohei et al. (2017) Calcium-Induced Morphological Transitions in Peptide Amphiphiles Detected by 19F-Magnetic Resonance Imaging. ACS Appl Mater Interfaces 9:39890-39894
Verma, Kirti Dhingra; Massing, Justin O; Kamper, Sarah G et al. (2017) Synthesis and evaluation of MR probes for targeted-reporter imaging. Chem Sci 8:5764-5768
Vistain, Luke F; Rotz, Matthew W; Rathore, Richa et al. (2016) Targeted delivery of gold nanoparticle contrast agents for reporting gene detection by magnetic resonance imaging. Chem Commun (Camb) 52:160-3
Preslar, Adam T; Tantakitti, Faifan; Park, Kitae et al. (2016) (19)F Magnetic Resonance Imaging Signals from Peptide Amphiphile Nanostructures Are Strongly Affected by Their Shape. ACS Nano 10:7376-84
MacRenaris, Keith W; Ma, Zhidong; Krueger, Ruby L et al. (2016) Cell-Permeable Esterase-Activated Ca(II)-Sensitive MRI Contrast Agent. Bioconjug Chem 27:465-73
Rammohan, Nikhil; MacRenaris, Keith W; Moore, Laura K et al. (2016) Nanodiamond-Gadolinium(III) Aggregates for Tracking Cancer Growth In Vivo at High Field. Nano Lett 16:7551-7564
Carney, Christiane E; MacRenaris, Keith W; Meade, Thomas J (2015) Water-soluble lipophilic MR contrast agents for cell membrane labeling. J Biol Inorg Chem 20:971-7

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