| |||||||||||||||||||||
 | |||||||||||||||||||||
Our laboratory is actively developing novel strategies for enzyme-mediated magnetic resonance imaging signal amplification (MRamp). To this end, we have developed a novel class of MR detectable sensing probes, i.e. chemical compounds that respond to the presence of a given molecule (enzymes and various low-molecular weight analytes) with a specific change in relaxation properties. One such imaging probe is di-5-HT-DTPAGd, a di-5-hydroxytryptamide of a commercially available paramagnetic MR contrast agent, DTPA(Gd). In the presence of endogenous oxidoreductase enzymes (which become elevated during the course of certain diseases), individual molecules of di-5-HT-DTPAGd will polymerize and be retained at the site of inflammation. The increase in MR signal (MRamp) which follows results from both an increase in the concentration of the paramagnetic contrast agent at the site of the enzyme, and from an inherent change in the relaxivity of the molecule. di-5-HT-DTPAGd is now available for investigational research on a multigram scale. We have also developed macrocyclic and open-chelate types of oxidoreductase-specific paramagnetic substrates. The use of “enzyme sensing” MR contrast agents is expected to have wide-spread utility for in vitro high throughput screening as well as for in vivo detection of antigen expression patterns. This research is currently funded by NIH (two RO1 grants). Our laboratory is focusing on two major applications: 1. Targeted imaging of cancer-specific molecules. 2. Imaging of myeloperoxidase activity in cardiovascular disease and cancer.
Collaborators: Dr. Matt Gounis, UMASS Dr. Ajay Wakhloo, UMASS Dr. Chris Sotak, Worcester Polytechnic Institute Dr. John W. Chen, Massachusetts General Hospital
Publications: Ronald JA, Chen JW, Chen Y, Hamilton AM, Rodriguez E, Reynolds F, Hegele RA, Rogers KA, Querol M, Bogdanov A, Weissleder R, Rutt BK. Enzyme-sensitive magnetic resonance imaging targeting myeloperoxidase identifies active inflammation in experimental rabbit atherosclerotic plaques. Circulation 2009, 120:592-9. Querol M, Bennett DG, Sotak C, Kang, HW, Bogdanov A Jr. A Paramagnetic Contrast Agent for Detecting Tyrosinase Activity. Chembiochem 2007 8: 1637-41. Chen JW, Querol Sans M, Bogdanov, A Jr, Weissleder R. Imaging inflammation: a multimodality molecular imaging approach targeting myeloperoxidase. Radiology 2006, 240:473-481. Querol M, Chen JW, Bogdanov A Jr. A paramagnetic contrast agent with myeloperoxidase-sensing properties Org Biomol Chem 2006, 4:1887-1895. | |||||||||||||||||||||
| |||||||||||||||||||||
 | |||||||||||||||||||||
 | Royal Society of Chemistry© | ||||||||||||||||||||
 | |||||||||||||||||||||
 | |||||||||||||||||||||
SPECT/CT image of MPO implant obtained using Ga-67 labeled substrate | |||||||||||||||||||||
MRI image of MPO implant using Gd-labeled substrate | |||||||||||||||||||||
 | | | | | | | | | | | | | | ||||||||
