PET Imaging of the AT1 receptor with [11C]KR31173

The goal of this study was to investigate the binding characteristics of [(11)C]KR31173 and its applicability for PET studies of the AT(1) receptor (AT(1)R).

Ex vivo biodistribution and pharmacology were tested in mice. PET imaging was performed in mice, beagle dogs and a baboon. To assess nonspecific binding, PET imaging was performed both before and after pretreatment with a potent AT(1)R antagonist. In the baboon, PET imaging was also performed with the previously developed radioligand [(11)C]L-159,884 for comparison.

Ex vivo biodistribution studies in mice showed specific binding rates of 80-90% in the adrenals, kidneys, lungs and heart. Specific binding was confirmed in mice using small animal PET. In dogs, renal cortex tissue concentration at 75-95 min postinjection (pi) was 63 nCi/ml per millicurie at a specific binding rate of 95%. In the baboon renal cortex, tissue activity at 55-75 min pi was 345 nCi/ml per millicurie. In the baboon the specific binding of [(11)C]KR31173 was higher (81%) than the specific binding of [(11)C]L-159,884 (34%).

[(11)C]KR31173 shows accumulation and significant specific binding to the AT(1)R in the kidneys of mice, dogs and baboon. These findings suggest that this radioligand is suited for imaging the renal cortical AT(1)R in multiple species.