In vivo magnetic resonance imaging of tumor protease activity

肿瘤蛋白酶活性的体内磁共振成像

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作者:Mohammad Haris, Anup Singh, Imran Mohammed, Ranjit Ittyerah, Kavindra Nath, Ravi Prakash Reddy Nanga, Catherine Debrosse, Feliks Kogan, Kejia Cai, Harish Poptani, Damodar Reddy, Hari Hariharan, Ravinder Reddy

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.

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