Hydrophilic fluorinated molecules for spectral 19F MRI

Abstract

Fluorine-19 (¹⁹F) Magnetic Resonance Imaging (MRI) is an emerging modality for molecular imaging and cell tracking. The hydrophobicity of current exogenous probes, perfluorocarbons (PFCs) and perfluoropolyethers (PFPEs), limits the formulation options available for in vivo applications. Hydrophilic probes permit more formulation flexibility. Further, the broad Nuclear Magnetic Resonance (NMR) chemical shift range of organofluorine species enables multiple probes with unique ¹⁹F MR signatures for simultaneous interrogation of distinct molecular targets in vivo. We report herein a flexible approach to stable liposomal formulations of hydrophilic fluorinated molecules (each bearing numerous magnetically equivalent ¹⁹F atoms), with ¹⁹F encapsulation of up to 22.7 mg/mL and a per particle load of 3.6 × 10^{6 19}F atoms. Using a combination of such probes, we demonstrate, with no chemical shift artifacts, the simultaneous imaging of multiple targets within a given target volume by spectral ¹⁹F MRI.