One-step 18F labeling of biomolecules using organotrifluoroborates

Herein we present a general protocol for the functionalization of biomolecules with an organotrifluoroborate moiety so that they can be radiolabeled with aqueous F-18 fluoride (F-18-) and used for positron emission tomography (PETPETPET) imaging. Among the beta+-emitting radionuclides, fluorine-18 (F-18) is the isotope of choice for PETPETPET, and it is produced, on-demand, in many hospitals worldwide. Organotrifluoroborates can be F-18-labeled in one step in aqueous conditions via F-18-F-19 isotope exchange. This protocol features a recently designed ammoniomethyltrifluoroborate, and it describes the following: (i) a synthetic strategy that affords modular synthesis of radiolabeling precursors via a copper-catalyzed 'click' reaction; and (ii) a one-step F-18-labeling method that obviates the need for HPLCPLCPLC purification. Within 30 min, F-18-labeled PETPETPET imaging probes, such as peptides, can be synthesized in good chemical and radiochemical purity (> 98%), satisfactory radiochemical yield of 20-35% (n > 20, non-decay corrected) and high specific activity of 40-111 GBq/mmol (1.1-3.0 Ci/mu mol). The entire procedure, including the precursor preparation and F-18 radiolabeling, takes 7-10 d.