Development of a novel [ F]fluorobenzyl derivative of the AT receptor antagonist Candesartan.

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