Pretargeted imaging of nanomedicines have attracted considerable interest because it has the potential to increase imaging contrast while reducing radiation burden to healthy tissue. Currently, the tetrazine ligation is the fastest bioorthogonal reaction for this strategy and, consequently, the state-of-art choice for in vivo chemistry. We have recently identified key properties for tetrazines in pretargeting. We have also developed a method to ¹⁸F-label reactive tetrazines using an aliphatic nucleophilic substitution strategy. Here, we combined this knowledge and developed an ¹⁸F-labeled tetrazine for pretargeted imaging. In order to develop this ligand, a small SAR study was performed. The most promising compound was selected for labeling and subsequent positron-emission-tomography in vivo imaging. Radiolabeling was achieved in satisfactory yields, molar activities, and high radiochemical purities. [¹⁸F]15 displayed favorable pharmacokinetics and remarkable target-to-background ratios—as early as 1 h post injection. We believe that this agent could be a promising candidate for translation into clinical studies.

中文翻译：

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开发第一个适用于预靶向 PET 成像的脂肪族 18F 标记四嗪 - 扩展生物正交工具箱

纳米药物的预定位成像引起了相当大的兴趣，因为它有可能增加成像对比度，同时减少对健康组织的辐射负担。目前，四嗪连接是该策略最快的生物正交反应，因此是体内化学的最新选择。我们最近确定了四嗪在预靶向中的关键特性。我们还开发了一种使用脂肪族亲核取代策略对¹⁸ F 标记反应性四嗪进行的方法。在这里，我们结合这些知识并开发了一个¹⁸用于预靶向成像的 F 标记四嗪。为了开发这种配体，进行了一项小型 SAR 研究。最有前途的化合物被选择用于标记和随后的正电子发射断层扫描体内成像。以令人满意的产率、摩尔活性和高放射化学纯度实现了放射性标记。[ ¹⁸ F] 15显示出良好的药代动力学和显着的靶点与背景比——早在注射后 1 小时。我们相信这种药物可能是转化为临床研究的有希望的候选者。