A practical protocol for large-scale copper-mediated radioiodination of organoboronic precursors: Radiosynthesis of [ I]KX-1 for Auger radiotherapy.

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 [ I]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, [ I]KX-1 was radiosynthesized from 20 mCi (0.74 GBq) of [ I]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.