A practical protocol for large-scale copper-mediated radioiodination of organoboronic precursors: Radiosynthesis of [123 I]KX-1 for Auger radiotherapy.
A practical protocol for large-scale copper-mediated radioiodination of organoboronic precursors: Radiosynthesis of [123 I]KX-1 for Auger radiotherapy.
复制标题
有机硼前体大规模铜介导放射性碘化的实用方案：用于俄歇放射治疗的 [123 I]KX-1 的放射合成。
DOI：
10.1002/jlcr.4065
复制
发表时间：
2023
影响因子：
1.8
通讯作者：
Xu,Jinbin
中科院分区：
文献类型：
--
作者：
Zhou,Dong;Chu,Wenhua;Xu,Jinbin
亲核铜介导的放射性碘化（CMRI）是一种很有前途的放射性碘化方法。先前报道的CMRI已经证明了其在放射性碘标记化合物的放射合成中的巨大潜力和标记范围。然而，报告的方案（使用少量/体积的放射性）在大规模CMRI中几乎不可重现，其中放射性通常以散装碱性溶液提供。大量的水和强碱与CMRI不相容。为了克服大规模CMRI中的这些问题，我们为大规模CMRI开发了一个简单的协议。在110°C下在惰性气体流下除去大部分水，并将强碱（即，用酸、吡啶钥对甲苯磺酸盐或对甲苯磺酸中和反应混合物（用NaOH中和）。在[123 I]KX-1（一种用于俄歇放射治疗的PARP-1放射性配体）的模型反应中，碱中和后放射化学转化率显著提高，并且添加额外的酸是耐受的，有利于反应。使用该方案，从20 mCi（0.74 GBq）的[123 I]碘化物以高放射化学产率、高放射化学纯度和高摩尔活性放射合成[123 I]KX-1。该方案应适用于通过CMRI与放射性碘放射合成其他化合物。
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, pyridiniump‐toluenesulfonate orp‐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.