PET imaging of human cardiac opioid receptors

Abstract

The presence of opioid peptides and receptors and their role in the regulation of cardiovascular function has been previously demonstrated in the mammalian heart. The aim of this study was to image micro and delta opioid receptors in the human heart using positron emission tomography (PET). Five subjects (three females, two males, 65+/-8 years old) underwent PET scanning of the chest with [(11)C]carfentanil ([(11)C]CFN) and [(11)C]- N-methyl-naltrindole ([(11)C]MeNTI) and the images were analyzed for evidence of opioid receptor binding in the heart. Either [(11)C]CFN or [(11)C]MeNTI (20 mCi) was injected i.v. with subsequent dynamic acquisitions over 90 min. For the blocking studies, either 0.2 mg/kg or 1 mg/kg of naloxone was injected i.v. 5 min prior to the injection of [(11)C]CFN and [(11)C]MeNTI, respectively. Regions of interest were placed over the left ventricle, left ventricular chamber, lung and skeletal muscle. Graphical analysis demonstrated average baseline myocardial binding potentials (BP) of 4.37+/-0.91 with [(11)C]CFN and 3.86+/-0.60 with [(11)C]MeNTI. Administration of 0.2 mg/kg naloxone prior to [(11)C]CFN produced a 25% reduction in BP in one subject in comparison with baseline values, and a 19% decrease in myocardial distribution volume (DV). Administration of 1 mg/kg of naloxone before [(11)C]MeNTI in another subject produced a 14% decrease in BP and a 21% decrease in the myocardial DV. These results demonstrate the ability to image these receptors in vivo by PET. PET imaging of cardiac opioid receptors may help to better understand their role in cardiovascular pathophysiology and the effect of abuse of opioids and drugs on heart function.

Effect and Safety of Morphine Use in Acute Anterior ST‐Segment Elevation Myocardial Infarction

“…In experimental models of ischemia reperfusion injury, morphine inhibits the mitochondrial permeability transition pore24 opening through μ and κ myocardial opioid receptors,25, 26 and induced a significant cardioprotective effect 27. Morphine also stimulates the reperfusion injury salvage kinase pathway 24.…”

Mediating δ-opioid-initiated heart protection via the β2-adrenergic receptor: role of the intrinsic cardiac adrenergic cell

“…Although ␦-opioid agonists exert potent cardioprotection, it is unclear which type of cardiac cells actually express ␦-opioid receptor (DOR). Despite the receptor-binding study of DOR (11,27,33) and its gene expression in human and animal hearts (2, 28), no clear immunohistochemical evidence has demonstrated in situ DOR expression in cardiac myocytes. The intrinsic cardiac adrenergic (ICA) cell is a neuroendocrine cell that expresses genes and enzyme proteins for epinephrine biosynthesis (5, 9, 10).…”

Synthesis of a Potent and Selective 18F-Labeled δ-Opioid Receptor Antagonist Derived from the Dmt-Tic Pharmacophore for Positron Emission Tomography Imaging

“…At present, there is an increasing demand of radioligands for in vivo imaging studies of peripheral opioid receptors to help assess the roles they may play in cancer, cardiovascular disease, gastrointestinal disorders, and pain relief. 24 The feasibility of imaging δ-opioid receptors in normal human heart, 25 , fluorescamine (Hoffman-La Roche) and chlorine spray reagents. Melting points were determined on a Kofler apparatus and are uncorrected.…”