One-Pot Multi-Tracer Synthesis of Novel 18F-Labeled PET Imaging Agents

F-18 labeled phosphonium salts are increasingly important molecular probes for targeting the mitochondrial membrane potential depletion during apoptosis and for detecting myocardial perfusion deficit. Here, we introduce three new tracers, [F-18]MitoPhos_04, [F-18]MitoPhos_05, and [F-18]MitoPhos_07, that have the potential to act as mitochondrial imaging agents. Moreover, they have the added advantage of being synthesized in the same reaction vial from one radiolabeled synthon, demonstrating a new approach to synthesizing multiple tracers in one-pot, which is a highly useful means for increasing the throughput of radiotracer development. The radiosynthesis of the tracers was carried out on a fully automated system via a facile two-step reaction. Utilizing the radiolabeling of an ethyl azide, a copper-mediated 1,3-cycloaddition reaction and isolation via semiprep high-performance liquid chromatography (HPLC) allowed for the simultaneous synthesis of two or three tracers with a total synthesis time of less than 1 h.