Molecular oxygen loading in candidate theranostic droplets stabilized with biocompatible fluorinated surfactants: Particle size effect and application to in situ19F MRI mapping of oxygen partial pressure.

OBJECTIVE: Perfluorocarbon nano- and micron-sized emulsions are a new field of investigation in cancer treatment due to their ability to be used as imaging contrast agents, or as delivery vectors for pharmaceuticals. They also demonstrated capability to enhance the efficiency of high intensity focused ultrasound thermo-therapy. In the context of new biomedical applications we investigated perfluorooctyl bromide (PFOB) theranostic droplets using 19F NMR. Each droplet contains biocompatible fluorinated surfactants composed of a polar Tris(hydroxymethyl)aminomethane head unit and hydrophobic perfluorinated tail (abbreviated as F-TAC). The influence of the droplet size on the oxygen loading capacity was determined from longitudinal relaxation (T1) data of 19F NMR signal. MATERIAL AND METHODS: Liquid PFOB and five samples of PFOB droplets of average diameter 0.177, 0.259, 1.43, 3.12 and 4.53 µm were tested with different oxygen levels. A dedicated gas exchange system was validated to maintain steady state oxygen concentrations, including a spatial gradient of oxygen concentration. A prototyped transmit-receive switchable 19F/1H quadrature coil was integrated on a 3 T clinical scanner. The coil is compatible with focused ultrasound sonication for future application. A spectroscopy FID inversion-recovery (IR) sequence was used to measure the T1 value per sample and per value of equilibrium oxygen pressure. Pixel wise, spatial T1 mapping was performed with magnetization prepared 2D gradient echo sequences in tissue mimicking gels doped with theranostic droplets. RESULTS: Experimental data indicated that the longitudinal relaxation rate of 19F signal of the investigated theranostic droplets depended approximately linearly on the oxygen level and its slope decreased with the particle size according to a second order polynomial over the investigated range. This semi-empirical model was derived from general thermodynamics and weak electrostatic forces theory and fitted the experimental data within 0.75% precision. The capacity of oxygen transportation for the described theranostic droplets tended to that of pure PFOB, while micron-sized droplets lost up to 50% of this capacity. In a specific setup producing a steady state gradient of oxygen concentration, we demonstrated spatial mapping of oxygen pressure gradient of 6 kPa/mm with 1 mm in-plane resolution. CONCLUSION: The size-tunable PFOB theranostic droplets stabilized with F-TAC surfactants could be characterized by 19F MRI in a clinical setup readily compatible with interventional in vivo studies under MR guidance. Current precision and spatial resolution of T1 mapping are promising. A potential challenge for further in vivo studies is the reduction of the imaging time.