In vivo labeling of angiotensin II receptors with a carbon-11-labeled selective nonpeptide antagonist

Sang Eun Kim, Ursula Scheffel, Zsolt Szabo, H. Donald Burns, Raymond E. Gibson, Hayden T. Ravert, William B. Mathews, Terence G. Hamill, Robert F. Dannals

Research output: Contribution to journalArticlepeer-review

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 (>29% in 90 min), with less than 8% excreted through the urine. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)307-311
Number of pages5
JournalJournal of Nuclear Medicine
Volume37
Issue number2
StatePublished - Feb 1 1996

Keywords

  • PET
  • angiotensin II receptors
  • carbon-11-L-159,884

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

Fingerprint

Dive into the research topics of 'In vivo labeling of angiotensin II receptors with a carbon-11-labeled selective nonpeptide antagonist'. Together they form a unique fingerprint.

Cite this