Novel O-[11C]methylated derivatives of candesartan as angiotensin II AT1 receptor imaging ligands: Radiosynthesis and ex vivo evaluation in rats

[11C]Methyl-candesartan and its desethyl derivative ([11C]TH4) were developed as potential radiotracers for imaging angiotensin II (Ang II) type 1 (AT1) receptors. These compounds were synthesized via methylation of tetrazole-protected candesartan using [11C]methyl iodide followed by deprotection through HCl hydrolysis at 65 °C to produce [11C]methyl-candesartan, and 90 °C for [11C]TH4. Ex vivo biodistribution and competition studies were carried out for both [11C]methyl-candesartan and [11C]TH4 to assess tissue retention time course and binding selectivity. Besides the liver, [11C]methyl-candesartan and [11C]TH4 displayed highest tissue retention in the AT1 receptor-rich renal cortex and outer medulla. At tracer doses 15 min post-injection, [11C]methyl-candesartan demonstrated higher specific binding proportion for AT1 receptors, and selectivity for AT1 over Ang II AT2, Mas, β-adrenergic, and α2-adrenergic receptors in rat kidneys compared to [11C]TH4. This study indicates that [11C]methyl-candesartan has potential for in vivo imaging renal AT1 receptors selectively using positron emission tomography.

Two novel radiotracers ([11C]methyl-candesartan and its desethyl derivative ([11C]TH4)) were synthesized via 11C-methylation of the tetrazole-protected candesartan as potential imaging agents for angiotensin II AT1 receptors.Figure optionsDownload as PowerPoint slide