MOLECULAR ENGINEERING OF ¹⁹F-BIOSENSORS FOR MR IMAGING

In MRI, information is most commonly obtained by enhancing the contrast between the target and its surrounding tissue. This contrast can be enhanced by either manipulating the imaging acquisition parameters or by introducing chemical or biological entities also known as contrast agents. For many years, gadolinium (Gd³⁺)-based probes and superparamagnetic iron oxide (SPIO)-based particles have been used to affect water relaxation properties (T₁ and T₂ or T₂*) and, consequently, the localized MR image contrast. Contrary to conventional contrast agents that affect water relaxation properties, ¹⁹F-based sensors may be used as imaging tracers. Due to the fact that ¹⁹F nuclei do not exist in biological tissues, the signal obtained from introduced ¹⁹F-biosensors can be overlaid on ¹H MRI anatomical information and be presented as a “hot-spot” map. Our lab aims to develop, optimize, and implement novel ¹⁹F-molecular tracers for molecular and cellular MR imaging applications. Here we show that the combination of two methodologies for molecular MRI, i.e., CEST-MRI (chemical exchange saturation transfer) and ¹⁹F-MRI (non-¹H), opened a new avenue for the design of MRI sensors, since it exploits the benefits of both methodologies. By understanding both the binding kinetics of ¹⁹F-based molecular systems and their NMR characteristics, novel platforms for ¹⁹F-CEST were designed and used. Specifically, we demonstrate (i) the use of such imaging platforms for spatially monitoring of metal ions with biological importance and (ii) a new concept for applying supramolecular systems for molecular MR imaging.