title: In vivo labeling of angiotensin II receptors with a carbon-11-labeled selective nonpeptide antagonist.
abstract: 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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Kim
authors.forename: U
authors.initials: U
authors.lastname: Scheffel
authors.forename: Z
authors.initials: Z
authors.lastname: Szabo
authors.forename: H D
authors.initials: HD
authors.lastname: Burns
authors.forename: R E
authors.initials: RE
authors.lastname: Gibson
authors.forename: H T
authors.initials: HT
authors.lastname: Ravert
authors.forename: W B
authors.initials: WB
authors.lastname: Mathews
authors.forename: T G
authors.initials: TG
authors.lastname: Hamill
authors.forename: R F
authors.initials: RF
authors.lastname: Dannals
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000818:Animals; D002250:Carbon Radioisotopes; D005069:Evaluation Studies as Topic; D006321:Heart / Q000000981:diagnostic imaging; D007093:Imidazoles / Q000493:pharmacokinetics; D007668:Kidney / Q000000981:diagnostic imaging; D008168:Lung / Q000000981:diagnostic imaging; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D011725:Pyridines / Q000493:pharmacokinetics; D011945:Receptors, Angiotensin / Q000032:analysis; D014018:Tissue Distribution; D014055:Tomography, Emission-Computed
chemical_list: D057911:Angiotensin Receptor Antagonists; D002250:Carbon Radioisotopes; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; C099071:L 159884