In vivo labeling of angiotensin II receptors with a carbon-11-labeled selective nonpeptide antagonist.
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.
Kim
S E
SE
Division of Nuclear Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
Scheffel
U
U
Szabo
Z
Z
Burns
H D
HD
Gibson
R E
RE
Ravert
H T
HT
Mathews
W B
WB
Hamill
T G
TG
Dannals
R F
RF
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
D057911:Angiotensin Receptor Antagonists; D002250:Carbon Radioisotopes; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; C099071:L 159884