Synthesis and biological evaluation of [ carboxyl ‐ 11 C]eprosartan

Essential hypertension occurs in approximately 25% of the adult population and one cause of hypertension is primary aldosteronism. Targeting the angiotensin II AT 1 receptor using PET and an appropriate tracer may offer a diagnostic method for adrenocortical tissue. This report describes the synthesis of the selective AT 1 receptor antagonist [ carboxyl ‐ 11 C]eprosartan 10, 4‐[2‐butyl‐5‐(( E )‐2‐carboxy‐3‐thiophen‐2‐yl‐propenyl)‐imidazol‐1‐ylmethyl]‐[ carboxyl ‐ 11 C]benzoic acid, and its precursor ( E )‐3‐[2‐butyl‐3‐(4‐iodo‐benzyl)‐3 H ‐imidazol‐4‐yl]‐2‐thiophen‐2‐ylmethyl‐acrylic acid 9. 11 C‐carboxylation of the iodobenzyl moiety was performed using a palladium‐mediated reaction with [ 11 C]carbon monoxide in the presence of tetra‐ n ‐butyl‐ammonium hydroxide in a micro‐autoclave using a temperature gradient from 25 to 140°C over 5 min. After purification by semipreparative HPLC, [ carboxyl ‐ 11 C]eprosartan 10 was obtained in 37–54% decay‐corrected radiochemical yield (from [ 11 C]carbon monoxide) with a radiochemical purity >95% within 35 min of the end of bombardment (EOB). A 5‐µAh bombardment gave 2.04 GBq of 10 (50% rcy from [ 11 C]carbon monoxide) with a specific activity of 160 GBq µmol −1 at 34 min after EOB. Frozen‐section autoradiography shows specific binding in kidney, lung and adrenal cortex. In vivo experiments in rats demonstrate a high accumulation in kidney, liver and intestinal wall. Copyright © 2009 John Wiley & Sons, Ltd.