Because of the importance of lacZ gene in various applications ranging from molecular biology to clinical trials, the development of non-invasive bimodal techniques for improving precision and accuracy to assay gene expression has attracted much attention. In this paper, we propose a dual-function probe for synergistic combination of ¹⁹F-MRS/¹H-MRI to simultaneously detect β-gal activity. Based on this strategy, we have designed, synthesized and characterized a series of ¹⁹F-MRS/¹H-MRI reporters, and demonstrated the feasibility of 1-O-(β-D-galactopyranosyl)-3-fluorocatechol MGD-3-FCAT for assessing β-gal activity in solution and in vitro with lacZ transfected tumor cells as well, by the characterization of β-gal responsive ¹⁹F-chemical shift changes Δδ_F, hydrolytic kinetics, and T₁, T₂ relaxation mapping.