By providing high spatial and temporal resolution in vivo images, PET imaging helps us realize the promise of personalized molecular medicine. Whereas the various nuclear properties make F18 a choice PET isotope, the chemical properties of fluoride complicate its use in biomolecular labelling such that 2-4 "hot" steps are required. Given the relatively short half-life of F18 (110 minutes), a rapid 1-step, reproducible, clean, and high yielding aqueous labelling of an intact biomolecule represents a long-standing challenge in the world of PET imaging. We hypothesized that biomolecules could be labelled via a pendent boronic ester in a single aqueous step whereby chemoselective F18-capture gives an in vivo stable F18-labeled trifluoroborate. While the B-F bond is considered to be one of the strongest single bonds on the periodic table, we used 19F-NMR and radioactive 18F-19F isotopic exchange assays to demonstrate that the B-F bond can be surprisingly labile, yet tuneable through chemical synthesis for applications in PET. Our findings have mechanistic implications for metal-mediated cross couplings and provide a rubric for developing a new class of boron reagents for expeditious PET 18F-labeling. Hence, we labelled several peptides, RGD, bisRGD, fluorescent peptide dimers, octreotate and other biomolecules, all of which are important imaging agents. Click reactions are also possible and taken together these results suggests that boron represents a viable platform for labelling most if not all biomolecules.

In search of kinetically stable aryltrifluoroborates: B-18F bond formation for one-step 18F-labeling of peptides for PET imaging

249th National Meeting (2015)

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