Synthesis and evaluation of a ¹¹C‐labelled angiotensin II AT₂ receptor ligand

Three 11 C‐radiolabelled high‐affinity nonpeptide AT 2 receptor‐selective ligands were synthesized and one of these was evaluated as positron emission tomography (PET) tracer. The labelling reaction was performed via palladium(0)‐mediated aminocarbonylation of the aryl iodide substrate using [ 11 C]carbon monoxide as the labelled precursor. As an example, starting with 10.0 GBq [ 11 C]carbon monoxide, 1.10 GBq of the product N ‐butoxycarbonyl‐3‐[4‐( N ‐benzyl‐[ 11 C]carbamoyl)‐phenyl]‐5‐isobutylthiophene‐2‐sulphonamide [ 11 C]4d was obtained in 36% decay‐corrected radiochemical yield (from [ 11 C]carbon monoxide), 42 min from end of bombardment with a specific activity of 110 GBq·µmol −1 . The N ‐isopropyl‐[ 11 C]carbamoyl‐analogue [ 11 C]4c (radiochemical purity >95%) was studied employing autoradiography, organ distribution, and small animal PET. In vitro autoradiography showed specific binding in the pancreas and kidney. Organ distribution in six rats revealed a high uptake in the liver, intestine, kidney, and adrenals. Small animal PET showed rapid and reversible uptake in the kidneys followed by accumulation in the urinary bladder suggesting fast renal excretion of the tracer. In addition, high accumulation was also seen in the liver. For future studies, more metabolically stable tracers will need to be developed. To the best of our knowledge, this is the first attempt of the use of PET imaging for the detection of expressed, fully functional AT 2 receptors in living subjects.