Radiobromine-labeled compounds can be used for positron emission tomography (PET) imaging (ie, <
sup>
76<
/sup>
Br) and for radiation therapy (ie, <
sup>
77<
/sup>
Br). However, the commonly used electrophilic substitution reaction using no-carrier-added radiobromide does not always afford the desired product due to the high reactivity of the brominating intermediate. A nucleophilic substitution by bromide, such as radiobromination of iodonium precursors, provides an alternative route for the synthesis of bromo-radiopharmaceuticals. The applicability of aromatic radiobromination by nucleophilic substitution using diaryliodonium salt precursors was evaluated using iodonium model compounds and [<
sup>
76<
/sup>
Br]/[<
sup>
77<
/sup>
Br]bromide. Radiobromination was observed under all conditions tested, in up to quantitative yields. A QMA cartridge treatment method and a base-free method have been developed, and no extra base is needed for either methods. The base-free conditions are mild and afford much cleaner reactions. Up to 20% water is tolerated in the reactions without reducing the radiochemical yields. No-carrier-added and carrier-added reactions afforded similar results. 4-Bromobenzaldehyde and 4-bromobenzoate have been radiosynthesized reliably and in good yields. Finally, these results indicate that this method is robust and efficient and thus will provide a route for radiobromination of electron-deficient arenes and an alternative route for the synthesis of bromo-radiopharmaceuticals for biological evaluations.