Nucleophilic copper‐mediated radioiodination (CMRI) of organoboronic precursors with radioiodides is a promising method of radioiodination. The previously reported CMRI has demonstrated its great potential and scope of labeling for the radiosynthesis of radioiodine‐labeled compounds. However, the reported protocols (using a small amount/volume of radioactivity) are practically not reproducible in large‐scale CMRI, in which the radioactivity was usually provided in a bulk alkaline solution. A large amount of water and a strong base are incompatible with CMRI. To overcome these issues in large‐scale CMRI, we have developed a simple protocol for large‐scale CMRI. The bulk water was removed under a flow of inert gas at 110°C, and the strong base (i.e., NaOH) was neutralized with an acid, pyridinium p‐toluenesulfonate or p‐toluenesulfonic acid. In the model reactions of [123I]KX‐1, a PARP‐1 radioligand for Auger radiotherapy, radiochemical conversions were significantly improved after neutralization of the base, and the addition of additional acids was tolerated and favorable for the reactions. Using this protocol, [123I]KX‐1 was radiosynthesized from 20 mCi (0.74 GBq) of [123I]iodide in high radiochemical yields, high radiochemical purity, and high molar activity. This protocol should be applicable to the radiosynthesis of other compounds with radioiodine via CMRI.