Designing kinetically stable aryltrifluoroborates as 18F‐capture agents for PET imaging

Abstract

One‐step 18F‐radiolabeling of peptides and other large biomolecules has been challenged by a critical gap in chemical compatibility between fluoride anion, which is unreactive as a nucleophile in water, and large biomolecules such as peptides that are insoluble in dry solvents. Traditionally, this disparity has been overcome through the preliminary synthesis of an 18F‐labeled radioprosthetic group that is appended to peptides following at least one additional step. Ideally, however, peptides should be labeled in a single aqueous step. Hence, we proposed the use of arylboronic acids as captors of aqueous 18F‐fluoride ion to simplify the radiosynthesis of 18F‐aryltrifluoroborate bioconjugates. Yet, the use of aryltrifluoroborates as radioprosthetic groups can only be considered if kinetically stable ones can be designed. Herein, we discuss the kinetic and thermodynamic parameters review our previous use of a Hammett analysis that can inform the design of kinetically stable 18F‐labeled aryltrifluoroborates for use as novel radioprosthetic groups. Copyright © 2014 John Wiley & Sons, Ltd.