Synthesis and biological evaluation of [carboxyl-¹¹C]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-C-11]eprosartan 10, 4-[2-butyl-5-((E)-2-carboxy-3-thiophen-2-yl-propenyl)-imidazol-1-ylmethyl]-[carboxyl-C-11]benzoic acid, and its precursor (E)-3-[2-butyl-3-(4-iodo-benzyl)-3H-imidazol-4-yl]-2-thiophen-2-ylmethyl-acrylic acid 9. C-11-carboxylation of the iodobenzyl moiety was performed using a palladium-mediated reaction with [C-11]carbon monoxide in the presence of tetra-n-butyl-ammonium hydroxide in a micro-autoclave using a temperature gradient from 25 to 140 degrees C over 5 min. After purification by semipreparative HPLC, [carboxyl-C-11]eprosartan 10 was obtained in 37-54% decay-corrected radiochemical yield (from [C-11]carbon monoxide) with a radiochemical purity >95% within 35 min of the end of bombardment (EOB). A 5-mu Ah bombardment gave 2.04 GBq of 10 (50% rcy from [C-11]carbon monoxide) with a specific activity of 160 GBq mu pmol(-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.