In Vivo Labeling of Angiotensin II Receptors with a Carbon-11-Labeled Selective Nonpeptide Antagonist

• Published in: The Journal of nuclear medicine (1978) Vol. 37; no. 2; pp. 307 - 311
• Main Authors: Kim, Sang Eun, Scheffel, Ursula, Szabo, Zsolt, Burns, H. Donald, Gibson, Raymond E, Ravert, Hayden T, Mathews, William B, Hamill, Terence G, Dannals, Robert
• Format: Journal Article
• Language: English
• Published: Reston, VA Soc Nuclear Med 01.02.1996; Society of Nuclear Medicine
• Subjects: Angiotensin Receptor Antagonists; Animals; Biological and medical sciences; Carbon Radioisotopes; Contrast media. Radiopharmaceuticals; Evaluation Studies as Topic; Heart - diagnostic imaging; Imidazoles - pharmacokinetics; Kidney - diagnostic imaging; Lung - diagnostic imaging; Male; Medical sciences; Mice; Mice, Inbred Strains; Pharmacology. Drug treatments; Pyridines - pharmacokinetics; Receptors, Angiotensin - analysis; Tissue Distribution; Tomography, Emission-Computed; Radionuclide study; Peptides; Rodentia; Experimental study; In vivo; Vertebrata; Biological fixation; Mammalia; Mouse; Animal; Kinetics; Angiotensin II; Positron; Hormonal receptor; Emission tomography
• ISSN: 0161-5505; 1535-5667

Angiotensin II (ANG II) initiates a variety of physiological effects by binding to high affinity receptors. Two ANG II receptor subtypes, AT1 and AT2, have recently been identified. This study was undertaken to evaluate [11C]L-159,884, an AT1 subtype selective nonpeptide antagonist, as a potential PET tracer. Carbon-11-L-159,884 was prepared by alkylation of the nor precursor with [11C]methyliodide and was studied for its in vivo binding characteristics, biodistribution and kinetics in mice. The effects of PD-123319, an AT2-selective ANGII antagonist, as well as those of alpha- and beta-adrenergic drugs on [11C]L-159,884 binding were investigated also. Administration of the AT1 antagonists resulted in dose-dependent inhibition of [11C]L-159,884 binding in the kidneys, the organ with the highest density of AT1 receptors. Inhibition was also observed in the lungs and the heart. Adrenergic drugs did not influence [11C]L-159,884 binding to AT1 receptors. Kinetic studies showed rapid tracer uptake in the liver, kidneys, lungs and heart. Excretion of the radioactivity occurred primarily through the intestinal tract (> 20% in 90 min), with less than 8% excreted through the urine. The results suggest that [11C]L-159,884 binds in vivo to AT1 receptors in mouse kidneys, lungs and heart. This radiotracer appears to be a promising candidate for studying ANG II receptors in vivo by PET.