In vivo visualization of gene expression using magnetic resonance imaging

High-resolution in vivo imaging of gene expression is not possible in opaqu e animals by existing techniques. Here we present a new approach for obtain ing such images by magnetic resonance imaging (MRI) using an MRI contrast a gent that can indicate reporter gene expression in living animals. We have prepared MRI contrast agents in which the access of water to the first coor dination sphere of a chelated paramagnetic ion is blocked with a substrate that can be removed by enzymatic cleavage. Following cleavage, the paramagn etic ion can interact directly with water protons to increase the MR signal . Here, we report an agent where galactopyranose is the blocking group. Thi s group renders the MRI contrast agent sensitive to expression of the commo nly used marker gene, P-galactosidase. To cellular resolution, regions of h igher intensity in the MR image correlate with regions expressing marker en zyme. These results offer the promise of in vivo mapping of gene expression in transgenic animals and validate a general approach for constructing a f amily of MRI contrast agents that respond to biological activity.