Strained tricyclic ring systems such as epoxides are rarely used as precursors for the introduction of anionic fluorine-18 into organic compounds intended for positron emission tomography (PET). Here we report the alpha selective ring opening of epoxides for the introduction of fluorine-18 into small as well as larger biomolecules via 1- and 2-step protocols. [ 18F]fluoromisonidazole ([ 18F]MISO), a tracer for hypoxia imaging, and the tumor targeting peptide Tyr 3-octreotate (TATE) were radiolabeled using epoxide opening reactions. In the latter case, the new prosthetic labeling synthon 4-(3-[ 18F]fluoro-2-hydroxypropoxy)benzaldehyde ([ 18F]FPB) has been used for 18F-introduction.