Evaluation of [11C]methyl-losartan and [11C]methyl-EXP3174 for PET imaging of renal AT1receptor in rats

IntroductionThe angiotensin II type 1 receptor (AT1R) is responsible for the main effects of the renin–angiotensin system (RAS), and its expression pattern is altered in several diseases. The [11C]methylated derivatives of the clinically used AT1R blocker (ARB) losartan and its active metabolite EXP3174, that binds with higher affinity to AT1R, were evaluated as potential PET imaging tracers in rat kidneys.Methods[11C]Methyl-losartan and [11C]methyl-EXP3174 were synthesized by [11C]methylation of the tetrazole-protected analogs using [11C]methyl iodide. Tissue uptake and binding selectivity of [11C]methyl-losartan were assessed by ex-vivo biodistribution and in-vitro autoradiography. Radiolabeled metabolites in rat plasma and kidneys were analysed by column-switch HPLC. Both tracers were evaluated with small animal PET imaging. Due to better pharmacokineti