Candesartan is a clinically approved angiotensin II type 1 receptor (AT₁R)‐blocker that selectively binds AT₁Rs in high affinity. We report here the radiosynthesis and automation of the novel [¹⁸F]fluorobenzyl derivative of Candesartan using the Sonogashira cross‐coupling reaction. [¹⁸F]Fluorobenzyl‐Candesartan ([¹⁸F]7) was developed from 4‐[¹⁸F]fluoroiodobenzene ([¹⁸F]FIB) that was conjugated with alkyne‐trityl‐candesartan with the assistance of a Pd (PPh₃)₄/CuI catalyst followed by acid deprotection. The three‐step two‐reactor 2‐HPLC purification process was automated resulting in >90% pure [¹⁸F]7 in a RCY of 4.6 ± 1.1% (decay corrected from EOB) and molar activities of 1,406‐5,513 GBq/mmol. [¹⁸F]FIB was reproducibly obtained by direct radiofluorination of the mono‐iodinated triphenylsulfonium salt in the presence of K222/K₂CO₃ in an ~30% yield (decay‐corrected). [¹⁸F]7 was stable (>97%) up to 4 h in solution and up to 1 h in rat plasma at 37°C. However, the use of Sonogashira cross‐coupling reaction to produce [¹⁸F]7 in high yields and molar activities was found to be challenging for routine use in radiochemistry labs.

中文翻译：

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AT1受体拮抗剂坎地沙坦的新型[18F]氟苄基衍生物的开发

坎地沙坦是一种临床批准的血管紧张素 II 1 型受体 (AT ₁ R) 阻滞剂，可选择性地以高亲和力结合 AT ₁ Rs。我们在此报告了使用 Sonogashira 交叉偶联反应的新型坎地沙坦 [ ^{18 F] 氟苄基衍生物的放射合成和自动化。}[ ¹⁸ F]氟苄基-坎地沙坦 ([ ¹⁸ F] 7 ) 由 4-[ ¹⁸ F]氟碘苯 ([ ^{18 F]FIB) 在 Pd (PPh} ₃ )的辅助下与炔烃-三苯甲基-坎地沙坦偶联而成₄/CuI 催化剂，然后进行酸脱保护。三步双反应器 2-HPLC 纯化过程是自动化的，产生 >90% 纯度的 [ ¹⁸ F] 7，RCY 为 4.6 ± 1.1%（从 EOB 校正的衰减）和 1,406-5,513 GBq/mmol 的摩尔活性。[ ¹⁸ F]FIB 是通过在 K222/K ₂ CO ₃存在下直接放射性氟化单碘化三苯基锍盐以约 30% 的产率（衰减校正）获得的。[ ¹⁸ F] 7在溶液中稳定 (>97%) 长达 4 小时，在 37°C 的大鼠血浆中长达 1 小时。然而，使用 Sonogashira 交叉偶联反应产生 [ ¹⁸ F] 7发现高产率和摩尔活性对于放射化学实验室的常规使用具有挑战性。