A Secreted Enzyme Reporter System for MRI

Abstract

An important goal in modern biology is to understand how molecular processes commonly studied at the cellular level give rise to physiological functions in complex tissues and organisms. Non-invasive imaging of gene-expression patterns in whole animals could provide information critical to this end, but current methods lack sensitivity and spatiotemporal precision. Enzymatic reporter systems detectable by magnetic resonance imaging (MRI) address these limitations by combining the relatively high spatial and temporal resolution of MRI with the ability of each genetically expressed enzyme to generate many MRI-detectable product molecules.1, 2 A challenge with the imaging-based detection of some of the most popular reporter enzymes is the need to deliver MRI probes to their sites of action within cells. Herein we describe a new reporter-gene system for MRI that relieves this problem by harnessing an extracellular enzyme, the mammalian secreted alkaline phosphatase (SEAP).