19 F MRI signal-enhancement by photo-chemically induced dynamic nuclear polarization enables spatially-resolved detection of sub-nmol amount of the antiviral drug favipiravir

Abstract

In biological tissues, 19F magnetic resonance (MR) enables the non-invasive, background-free detection of 19F-containing biomarkers. However, the signal-to-noise ratio (SNR) is usually low because biomarkers are typically present at low concentrations. Measurements at low magnetic fields further reduce the SNR. We therefore applied LED-based photo-chemically induced dynamic nuclear polarization (photo-CIDNP) to amplify the 19F signal at 0.6 T. For the first time, 19F MR imaging (MRI) and spectroscopy (MRS) of a fully biocompatible model system containing the antiviral drug favipiravir has been successfully performed. This fluorinated drug has been used to treat Ebola and COVID-19. Because the partially cyclic reaction scheme for photo-CIDNP allows for multiple data acquisitions, averaging further improved the SNR. The mean signal gain factor for 19F has been estimated to be around 1700. An in-plane resolution of 0.39 x 0.39 mm2 enabled the analysis of spatially varying degrees of hyperpolarization. The minimal detectable amount of favipiravir per voxel was about 500 pmol. The results show that 19F photo-CIDNP is a promising method for the non-invasive detection of suitable 19F-containing drugs and other compounds with very low levels of the substance, even when measured in low magnetic fields.