In vivo visualization of gene expression using magnetic resonance imaging

Abstract

High-resolution in vivo imaging of gene expression is not possible in opaque animals by existing techniques. Here we present a new approach for obtaining such images by magnetic resonance imaging (MRI) using an MRI contrast agent that can indicate reporter gene expression in living animals. We have prepared MRI contrast agents in which the access of water to the first coordination sphere of a chelated paramagnetic ion is blocked with a substrate that can be removed by enzymatic cleavage. Following cleavage, the paramagnetic ion can interact directly with water protons to increase the MR signal. Here, we report an agent where galactopyranose is the blocking group. This group renders the MRI contrast agent sensitive to expression of the commonly used marker gene, beta-galactosidase. To cellular resolution, regions of higher intensity in the MR image correlate with regions expressing marker enzyme. These results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a family of MRI contrast agents that respond to biological activity.

Superparamagnetic Iron Oxide Nanoparticle Probes for Molecular Imaging

“…While other embodiments for MR contrast agents exist, including different transition metal systems such as cobalt-ferrite 97 or soluble paramagnetic chelates, such as gadolinium, 40,84 they are outside the scope of this review and will not be discussed in depth. Rather, this review will focus specifically on the use of SPIO as a molecular imaging agent.…”

An Enzymatically Activated Fluorescence Probe for Targeted Tumor Imaging

“…A range of substrates has been developed including colorimetric, 12,13 fluororescence, 14-19 chemluminescence, 20,21 and paramagnetic probes, 22 though they have mostly been used in in vitro systems, with only a few successful applications in vivo. [23][24][25] In our previous work, we focused on simple, rapid, and sensitive detection of β-galactosidase activity, and developed a highly sensitive fluorescence probe for β-galactosidase, TG-βGal (Scheme 1a). 26 This probe was rationally designed to show a dramatic fluorescence activation (up to 440-fold) upon reaction with β-galactosidase, and was successfully used to visualize β-galactosidase activity in living cells.…”

Multimodal imaging of mouse development: Tools for the postgenomic era

“…Because of the noninvasive properties of MRI imaging and the ease of manipulating the mouse genome, it would be highly beneficial to have genetically encoded reporters for MRI imaging. The expression of gene products that can enhance iron uptake, such as tyrosinase (Weissleder et al, 1997) and transferrin receptor (Hogemann et al, 2000;Weissleder et al, 2000) have both been used successfully to label cells for MRI and substrates for existing reporters such as ␤-galactosidase have also been reported (Louie et al, 2000). Despite these encouraging advances, issues with toxicity, delivery, and cellular uptake have limited the use of these strategies (see Louie, 2006), but the quest continues for innocuous, genetically encoded MR contrast agents.…”