Novel Fe-Based H MRI -Galactosidase Reporter Molecules**.

There is increasing interest in the development of reporter agents to reveal enzyme activity using small animal imaging. We have previously demonstrated the feasibility of detecting gene activity using the commercially available 3,4-cyclohexenoesculetin-β--galactopyranoside (S-Gal™) as a H MRI reporter. Specifically, β-galactosidase (β-gal) releases the aglycone, which forms an MR contrast-inducing paramagnetic precipitate in the presence of Fe. Contrast was primarily T-weighted signal loss, but T effects were also observed. Since T-contrast generally provides signal enhancement as opposed to loss, it appeared attractive to explore whether analogues could be generated with enhanced characteristics. We now report the design and successful synthesis of novel analogues together with characterization of H MRI contrast based on both and response to β-gal activity for the lead agent.