Positron Emission Tomography (PET) Imaging of Opioid Receptors

Abstract

The opioid system consists of opioid receptors (which mediate the actions of opium), their endogenous ligands (the enkephalins, endorphins, endomorphins, dynorphin, and nociceptin), and the proteins involved in opioid production, transport, and degradation. PET tracers for the various opioid receptor subtypes are available, and changes in regional opioidergic activity have been assessed during both sensory and affective processing in healthy individuals and in various disease conditions such as chronic pain, neurodegeneration, epilepsy, eating disorders, behavioral addiction, and substance abuse. It is not always clear whether observed changes of tracer binding reflect altered release of endogenous opioids or altered opioid receptor expression. This issue may be resolved by studies in experimental animals that combine in vivo PET imaging with ex vivo immunohistochemistry. Some radioligands for opioid receptors have suboptimal kinetics (i.e., slow dissociation from their target protein) or can induce undesired side effects even at low administered doses (sedation, respiratory arrest). Yet, PET offers the unique opportunity of quantifying opioid receptor-mediated signaling in the living human brain. PET imaging has provided evidence for a link between opioid neurotransmission and peripheral immune activation.

Radiosynthesis of [11C]LY2795050 for Preclinical and Clinical PET Imaging Using Cu(II)-Mediated Cyanation

“…1 These receptors were first imaged in humans using positron emission tomography (PET) in the 1980s. 2 Since these early studies, significant work has been undertaken to develop radiotracers for quantifying the major opioid receptor subtypes (mu, delta, kappa, ORL-1). 3 Given that popular opioid pain killers such as morphine, codeine, and fentanyl all act preferentially at mu opioid receptors (MORs), 4,5 significant work has been undertaken to understand the pharmacology of this receptor.…”

“…Opioid receptors are involved in a variety of neuropsychiatric diseases and remain popular targets for imaging and drug development . These receptors were first imaged in humans using positron emission tomography (PET) in the 1980s . Since these early studies, significant work has been undertaken to develop radiotracers for quantifying the major opioid receptor subtypes (mu, delta, kappa, ORL-1) .…”