Imaging of enzymatic activity

US6737247B2 · kind B2 · utility

Assignee

• The General Hospital Corporation · US

Inventors

• Alexei Bogdanov · Arlington, US
• Ralph Weissleder · Peabody, US

Key dates

• Filing date: Oct 19, 2001
• Grant date: May 18, 2004
• Expiry date: Oct 19, 2021

Classification

• Technology area (CPC G): Physics
• CPC primary: G01R33/465
• WIPO field: Measurement
• WIPO sector: Instruments

Abstract

The invention features methods of detecting enzymatic activity (e.g., in a magnetic resonance image). In general, the methods include: (1) providing a monomeric substrate (e.g., a substrate that is polymerizable in the presence of an enzyme or as a result of an enzyme-catalyzed reaction), having the generic structure X-Y-Z, where X includes a chelator moiety having a chelated paramagnetic or superparamagnetic metal atom or ion, Y includes a linker moiety (e.g., to provide a covalent or non-covalent chemical bond or bonds between X and Z), and Z includes a polymerizing moiety; (2) contacting the substrate with a target tissue, wherein the substrate undergoes polymerization to form a paramagnetic or superparamagnetic polymer, the polymerization being catalyzed by an enzyme in an extracellular matrix or bound to the surfaces of cells of the target tissue; and (3) detecting an increase in relaxivity for the polymer relative to an equivalent amount of unpolymerized substrate. The invention also features substrate compositions.