Bench to Bedside: Chemistry of Health Care

Non-canonical Approaches to 18F-labeling: New Frontiers in Stable Non-carbon-fluorine Bonds (#337)

Positron Emission Tomography (PET) Imaging is a powerful technique for imaging specific pathologies, most prominently, cancer. Most tracers are large, water-soluble peptidic species that exhibit high selectivity yet clear rapidly to ensure high contrast tumor images. For PET imaging, one needs a robust labeling strategy to provide high yields and high specific activity. 18F-fluoride is often the isotope of choice owing to its excellent nuclear properties and on-demand production. Yet the low chemical reactivity of 18F-fluoride in water along with its 110 min half-life challenges production of 18F-labeled peptides. For two decades, most radiosynthetic efforts have focused on generating carbon-18F-fluorine bonds for radioprosthetics. In the past 8 years, new approaches recognize the strengths of non-carbon captors of fluoride that afford bonds nearly as stable as a C-F bond but which permit direct aqueous 18F-labeling. This emerging class of captors comprise boron, silicon, aluminum, phosphorus, sulfur and lanthanides as fluorophiles. These noncanonical fluorophiles provide exciting new avenues for developing PET radiotracers and interface subdisciplines of bioconjugate chemistry, radiochemistry, nanoscience, and inorganic chemistry. New captors raise the profile of bio-inorganic chemistry where interests in PET biology is amalgamated with other fields to address a long-standing challenge in 18F-radiosynthesis - namely a one-step high yielding and rapid 18F-labeling of biologically important ligands.
Last update: Dec 28, 2015