European Journal of Nuclear Medicine

, Volume 22, Issue 4, pp 339–345

Iodine-123N- methyl-4-iododexetimide: a new radioligand for single-photon emission tomographic imaging of myocardial muscarinic receptors

Authors

  • Rodney J. Hicks
    • Heidelberg Hospital
  • Michael Kassiou
    • Biomedicine and Health DivisionAustralian Nuclear Science and Technology Organisation
  • Peter Eu
    • Heidelberg Hospital
  • Andrew G. Katsifis
    • Biomedicine and Health DivisionAustralian Nuclear Science and Technology Organisation
  • Maria Garra
    • Heidelberg Hospital
  • John Power
    • Heidelberg Hospital
  • Ljubco Najdovski
    • Biomedicine and Health DivisionAustralian Nuclear Science and Technology Organisation
  • Richard M. Lambrecht
    • Biomedicine and Health DivisionAustralian Nuclear Science and Technology Organisation
Original article

DOI: 10.1007/BF00941851

Cite this article as:
Hicks, R.J., Kassiou, M., Eu, P. et al. Eur J Nucl Med (1995) 22: 339. doi:10.1007/BF00941851

Abstract

Cardiac muscarinic receptor ligands suitable for positron emission tomography have previously been characterised. Attempts to develop radioligands of these receptors suitable for single-photon emission tomographic (SPET) imaging have not been successful due to high lung retention and high non-specific binding of previously investigated potential tracers. The purpose of this study was to evaluate the biodistribution and in vivo imaging characteristics of a new radiopharmaceutical, [123I]N-methyl-4-iododexetimide. Biodistribution studies performed in rats showed high cardiac uptake (2.4% ID/g) 10 min after injection with a heart to lung activity ratio of 5:1. Specificity and stereo selectivity of cardiac binding were demonstrated using blocking experiments in rats. Dynamic imaging studies in anaesthetised greyhounds demonstrated rapid and high myocardial uptake and low lung binding with stable heart to lung activity ratios of >2.5:1 between 10 and 30 min, making SPET imaging feasible. Administration of an excess of an unlabelled muscarinic antagonist, methyl-quinuclidinyl benzylate rapidly displaced myocardial activity to background levels and the pharmacologically inactive enantiomer, [123I]N-methyl-4-iodolevetimide, had no detectable cardiac uptake, indicating specific and stereoselective muscarinic receptor binding. SPET revealed higher activity in the inferior than in the anterior wall, this being consistent with previously described regional variation of cardiac parasympathetic innervation. [123I]N-methyl-4-iododexetimide shows promise as an imaging agent for muscarinic receptor distribution in the heart and may be helpful in evaluating diverse cardiac diseases associated with altered muscarinic receptor function, including heart failure and diabetic heart disease.

Key words

Muscarinic receptorParasympathetic nervous systemSingle-photon emission tomographyCardiac uptake

Copyright information

© Springer-Verlag 1995