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New Concepts in Molecular Imaging: Non-Invasive MRI Spotting of Proteolysis Using an Overhauser Effect Switch
- Source :
- PLoS ONE, PLoS ONE, Public Library of Science, 2009, 4 (4), pp. 1-9. ⟨10.1371/journal.pone.0005244⟩, PLoS ONE, 2009, 4 (4), pp. 1-9. ⟨10.1371/journal.pone.0005244⟩, PLoS ONE, Vol 4, Iss 4, p e5244 (2009)
- Publication Year :
- 2009
- Publisher :
- HAL CCSD, 2009.
-
Abstract
- 9 pages; International audience; Background: Proteolysis, involved in many processes in living organisms, is tightly regulated in space and time under physiological conditions. However deregulation can occur with local persistent proteolytic activities, e.g. in inflammation, cystic fibrosis, tumors, or pancreatitis. Furthermore, little is known about the role of many proteases, hence there is a need of new imaging methods to visualize specifically normal or disease-related proteolysis in intact bodies. Methodology/Principal Findings: In this paper, a new concept for non invasive proteolysis imaging is proposed. Overhauser-enhanced Magnetic Resonance Imaging (OMRI) at 0.2 Tesla was used to monitor the enzymatic hydrolysis of a nitroxide-labeled protein. In vitro, image intensity switched from 1 to 25 upon proteolysis due to the associated decrease in the motional correlation time of the substrate. The OMRI experimental device used in this study is consistent with protease imaging in mice at 0.2 T without significant heating. Simulations show that this enzymatic-driven OMRI signal switch can be obtained at lower frequencies suitable for larger animals or humans. Conclusions/Significance: The method is highly sensitive and makes possible proteolysis imaging in three dimensions with a good spatial resolution. Any protease could be targeted specifically through the use of taylor-made cleavable macromolecules. At short term OMRI of proteolysis may be applied to basic research as well as to evaluate therapeutic treatments in small animal models of experimental diseases.
- Subjects :
- Diagnostic Imaging
Proteases
Proteolysis
medicine.medical_treatment
[PHYS.PHYS.PHYS-BIO-PH]Physics [physics]/Physics [physics]/Biological Physics [physics.bio-ph]
lcsh:Medicine
Biochemistry/Biocatalysis
Free radicals
Imaging techniques
010402 general chemistry
01 natural sciences
Biochemistry
Models, Biological
Magnetic resonance imaging
Electron spin resonance spectroscopy
medicine
Medical imaging
Animals
Cysteine
Biophysics/Biocatalysis
lcsh:Science
Biochemistry/Experimental Biophysical Methods
Multidisciplinary
Protease
Cysteine proteases
medicine.diagnostic_test
010405 organic chemistry
Hydrolysis
lcsh:R
Radiology and Medical Imaging/Magnetic Resonance Imaging
Proteins
Serum Albumin, Bovine
Mathematical Concepts
In vitro
0104 chemical sciences
In vivo imaging
Biophysics
lcsh:Q
Cattle
Nitrogen Oxides
Molecular imaging
Preclinical imaging
Research Article
Peptide Hydrolases
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Database :
- OpenAIRE
- Journal :
- PLoS ONE, PLoS ONE, Public Library of Science, 2009, 4 (4), pp. 1-9. ⟨10.1371/journal.pone.0005244⟩, PLoS ONE, 2009, 4 (4), pp. 1-9. ⟨10.1371/journal.pone.0005244⟩, PLoS ONE, Vol 4, Iss 4, p e5244 (2009)
- Accession number :
- edsair.doi.dedup.....65e9d9b98d8853e1568520444e50fc50