Development of a Highly Responsive Organofluorine Temperature Sensor for ¹⁹F Magnetic Resonance Applications

Temperature can affect many biological and chemical processes within a body. During in vivo measurements, varied temperature can impact the accurate quantification of additional abiotic factors such as oxygen. During magnetic resonance imaging (MRI) measurements, the temperature of the sample can increase with the absorption of radiofrequency energy, which needs to be well-regulated for thermal therapies and long exposure. To address this potentially confounding effect, temperature can be probed intentionally using reporter molecules to determine the temperature in vivo. This work describes a combined experimental and computational approach for the design of fluorinated molecular temperature sensors with the potential to improve the accuracy and sensitivity of 19F MRI-based temperature monitoring. These fluorinated sensors are being developed to overcome the temperature sensitivity and tissue limitations of the proton resonance frequency (10 × 10-3 ppm °C-1), a standard parameter used for temperature mapping in MRI. Here, we develop (perfluoro-[1,1′-biphenyl]-4,4′-diyl)bis((heptadecafluorodecyl)sulfane), which has a nearly 2-fold increase in temperature responsiveness, compared to the proton resonance frequency and the 19F MRI temperature sensor perfluorotributylamine, when tested under identical NMR conditions. While 19F MRI is in the early stages of translation into clinical practice, development of alternative sensors with improved diagnostic abilities will help advance the development and incorporation of fluorine magnetic resonance techniques for clinical use.