Development Of A Novel [F-18]Fluorobenzyl Derivative Of The At(1) Receptor Antagonist Candesartan

Candesartan is a clinically approved angiotensin II type 1 receptor (AT(1)R)-blocker that selectively binds AT(1)Rs in high affinity. We report here the radiosynthesis and automation of the novel [F-18]fluorobenzyl derivative of Candesartan using the Sonogashira cross-coupling reaction. [F-18]Fluorobenzyl-Candesartan ([F-18]7) was developed from 4-[F-18]fluoroiodobenzene ([F-18]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 [F-18]7 in a RCY of 4.6 +/- 1.1% (decay corrected from EOB) and molar activities of 1,406-5,513 GBq/mmol. [F-18]FIB was reproducibly obtained by direct radiofluorination of the mono-iodinated triphenylsulfonium salt in the presence of K222/K2CO3 in an similar to 30% yield (decay-corrected). [F-18]7 was stable (>97%) up to 4 h in solution and up to 1 h in rat plasma at 37 degrees C. However, the use of Sonogashira cross-coupling reaction to produce [F-18]7 in high yields and molar activities was found to be challenging for routine use in radiochemistry labs.