Investigation of angiotensin II/AT₁ receptors with carbon-11-L-159,884: A selective antagonist

Antagonists of the angiotensin II AT₁ receptor subtype have been recently introduced for treatment of arterial hypertension and for pharmacological studies of these receptors. The purpose of this work was to label such an antagonist with ¹¹C and test the applicability of the radioligand for PET studies. Methods: The potent and selective nonpeptide AT₁ antagonist L-159,884 was labeled with ¹¹C and injected intravenously into six dogs. Renal accumulation and kinetics of the radioligand were imaged with PET at baseline and after receptor blockade with 1 mg/kg MK-996. Time- activity curves were derived from the renal cortex and were analyzed by the Gjedde-Patlak plot to obtain the influx rate constant of the radioligand. Results: There was selective radioligand binding in the kidneys, mainly located in the Cortex. Within the time interval between 95 and 115 min postinjection, the radioactivity retained in the kidneys was 109 ± 27 and 42 ± 4 nCi/ml/mCi of the injected dose for the control and inhibition studies, respectively. The influx rate constant of the radioligand decreased from a baseline of 0.0298 ± 0.0156 to a post-MK-996 value of 0.0098 ± 0.0052. Conclusion: These results demonstrate distinct binding of ¹¹C-L-159,884 in the renal cortex with a specific binding component suitable for quantitative PET imaging of angiotensin II/AT1 receptors.