Novel Molecular Platform Integrated Iron Chelation Therapy for ¹H‑MRI Detection of β‑Galactosidase Activity

Targeting the increased Fe³⁺ content in tumors, we propose a novel molecular platform integrated cancer iron chelation therapy for ¹H-magnetic resonance imaging (MRI) detection of β-galactosidase (β-gal) activity. Following this idea, we have designed, synthesized, and characterized a series of β-d-galactosides conjugated with various chelators and demonstrated the feasibility of this concept for assessing β-gal activity in solution by ¹H-MRI <i>T</i>₁ and <i>T</i>₂ relaxation mapping

Dual ¹⁹F/¹H MR Gene Reporter Molecules for <i>in Vivo</i> Detection of β-Galactosidase

Increased emphasis on personalized medicine and novel therapies requires the development of noninvasive strategies for assessing biochemistry <i>in vivo</i>. The detection of enzyme activity and gene expression <i>in vivo</i> is potentially important for the characterization of diseases and gene therapy. Magnetic resonance imaging (MRI) is a particularly promising tool, since it is noninvasive and has no associated radioactivity, yet penetrates deep tissue. We now demonstrate a novel class of dual ¹H/¹⁹F nuclear magnetic resonance (NMR) <i>lacZ</i> gene reporter molecule to specifically reveal enzyme activity in human tumor xenografts growing in mice. We report the design, synthesis, and characterization of six novel molecules and evaluation of the most effective reporter in mice <i>in vivo</i>. Substrates show a single ¹⁹F NMR signal and exposure to β-galactosidase induces a large ¹⁹F NMR chemical shift response. In the presence of ferric ions, the liberated aglycone generates intense proton MRI T₂ contrast. The dual modality approach allows both the detection of substrate and the imaging of product enhancing the confidence in enzyme detection