Symmetry‐Guided Design and Fluorous Synthesis of a Stable and Rapidly Excreted Imaging Tracer for ¹⁹F MRI

Abstract

Getting FIT: A bispherical (19)F imaging tracer, (19)FIT, was designed and synthesized. (19)FIT is advantageous over perfluorocarbon-based (19)F imaging agents, as it is not retained in the organs and does not require complex formulation procedures. Imaging agents such as (19)FIT can lead to (19)F magnetic resonance imaging (MRI) playing an important role in drug therapy, analogous to the role played by (1)H MRI in disease diagnosis.

In Vivo Magnetic Resonance Imaging to Detect Biliary Excretion of 19F-Labeled Drug in Mice

“…19 F is second only to 1 H in sensitivity for MRI, and background 19 F signals in animals and humans are negligible (Jiang et al, 2009). Positron emission tomography was considered but rejected for this purpose because positron emission tomography probes are radioactive (e.g., 18 F), are more costly (a cyclotron is needed to create 18 F for each use), and have short radiation half-lives (109 min for 18 F).…”

“…Positron emission tomography was considered but rejected for this purpose because positron emission tomography probes are radioactive (e.g., 18 F), are more costly (a cyclotron is needed to create 18 F for each use), and have short radiation half-lives (109 min for 18 F). In mice, stable nonradioactive 19 F-labeled tracers can be imaged for days (Jiang et al, 2009). …”

19F MRI Probes with Tunable Switches and Highly Sensitive 19F MRI Nanoprobes

“…To overcome this low sensitivity, increasing the number of 19 F is one solution. 9 However, if the number of 19 F is simply multiplied, due to the increase of hydrophobicity the interaction with serum protein or lipid also increases, and from this interaction both molecular motility and the delivery efficiency to the place of interest is hindered. 10 Among these, inhibition of molecular motility results in the shortening of T 2 and in the decrease of sensitivity.…”

Fluorine is Flourishing in Pharmaceuticals

“…In the field of pharmaceuticals, introducing a fluorine atom or fluorinated group into drugs or drug leads is often accompanied with higher binding affinity, enhanced metabolic stability, improved bioavailability, and sometimes, increased selective activity. Additionally, the development and therapeutic monitoring of fluorinated drugs can be facilitated by additional techniques, such as F MRI/S and fluorous technology [9][10][11][12], fluorine is playing an ever more important role in pharmaceuticals. First, fluorination has become an established strategy to modify physical properties, binding characteristics and metabolic disposition during drug leads development.…”

“…F MRI has recently been used successfully in tracing therapeutic cells [11] and drug delivery systems [12] with high spatial and temporal resolution. Such proof of concept research indicates 19 F MRI is a valuable tool for imaging-guided drug delivery and personalized drug therapy.…”