title: In vivo magnetic resonance imaging of tumor protease activity.
abstract: Increased expression of cathepsins has diagnostic as well as prognostic value in several types of cancer. Here, we demonstrate a novel magnetic resonance imaging (MRI) method, which uses poly-L-glutamate (PLG) as an MRI probe to map cathepsin expression in vivo, in a rat brain tumor model. This noninvasive, high-resolution and non-radioactive method exploits the differences in the CEST signals of PLG in the native form and cathepsin mediated cleaved form. The method was validated in phantoms with known physiological concentrations, in tumor cells and in an animal model of brain tumor along with immunohistochemical analysis. Potential applications in tumor diagnosis and evaluation of therapeutic response are outlined.
authors.affiliation: 1] Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA [2] Research Branch, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Haris
authors.affiliation: 1] Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA [2] Centre for Biomedical Engineering, Indian Institute of Technology Delhi, New Delhi, 110016, India.
authors.forename: Anup
authors.initials: A
authors.lastname: Singh
authors.affiliation: Department of Pharmacology and Institute for Translational Medicine and Therapeutics, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Imran
authors.initials: I
authors.lastname: Mohammed
authors.affiliation: Molecular Imaging, Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ittyerah
authors.affiliation: Molecular Imaging, Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Kavindra
authors.initials: K
authors.lastname: Nath
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Ravi Prakash Reddy
authors.initials: RP
authors.lastname: Nanga
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Debrosse
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Feliks
authors.initials: F
authors.lastname: Kogan
authors.affiliation: 1] Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA [2] CMRR 3T Research Program, Department of Radiology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Kejia
authors.initials: K
authors.lastname: Cai
authors.affiliation: Molecular Imaging, Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Harish
authors.initials: H
authors.lastname: Poptani
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Damodar
authors.initials: D
authors.lastname: Reddy
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Hari
authors.initials: H
authors.lastname: Hariharan
authors.affiliation: Center for Magnetic Resonance and Optical Imaging, Department of Radiology, University of Pennsylvania, Philadelphia, PA, 19104, USA.
authors.forename: Ravinder
authors.initials: R
authors.lastname: Reddy
mesh_terms: D000818:Animals; D002403:Cathepsins / Q000032:analysis* / Q000096:biosynthesis; D045744:Cell Line, Tumor; D003287:Contrast Media / Q000737:chemistry*; D005260:Female; D018316:Gliosarcoma / Q000000981:diagnostic imaging*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D019047:Phantoms, Imaging; D011099:Polyglutamic Acid / Q000737:chemistry*; D011859:Radiography; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D003287:Contrast Media; D011099:Polyglutamic Acid; D002403:Cathepsins