Opioids such as morphine are analgesics commonly used in clinical practice. Three opioid receptors (mu, µ; delta, δ; and kappa, κ) that mediate opioid effects have been identified by molecular cloning: δ (enkephalin-preferring), κ (dynorphin-preferring), and µ (ß-endorphin-preferring) (1). Pharmacological studies suggest that each type of opioid receptor consists of subtypes of receptors (2, 3). Their specificity and ubiquitous location are present in both the central and peripheral nervous system. The opioid receptors (G-protein-coupled, resulting in decrease in adenylyl cyclase activity) play an important role in the regulation of analgesia, shock, appetite, thermoregulation, and cardiovascular, mental and endocrine function (2-5). Although the µ opioid receptor is the major receptor to mediate the analgesic effects of opioids, δ and κ receptors are also important in antinociception. Opioids have been found to protect cells from ischemic injury in the heart and brain via the δ receptors. On the other hand, κ antagonists prevent neurodegeneration.
In humans, the κ opioid receptors (κ1 and κ2 ) are the most abundant brain opioid receptors and are widely distributed in deeper layers of the neocortex (particularly the temporal, parietal, and frontal cortices), striatum, and thalamus, with lower levels in the amygdala, hippocampus, occipital cortex, and cerebellum (6-8). The κ opioid receptors have been implicated in several clinical brain disorders, including drug abuse (9), epilepsy (10), Tourette’s syndrome (11), and Alzheimer’s disease (12).
Diprenorphine is a highly potent and nonselective opioid receptors antagonist with subnanomolar affinity (13). Diprenorphine has been labeled as [6-O-methyl-11C]diprenorphine ([11C]DPN) (14, 15). [11C]DPN is being developed as a positron emission tomography (PET) agent for the non-invasive study of opioid receptors in the brain. However, [11C]DPN PET studies are complicated by the 20.4 min short half-life (t1/2) of 11C. 6-O-(2-[18F]Fluoroethyl)-6-O-desmethyldiprenorphine ([18F]FDPN) has been synthesized as a 18F (t1/2 = 110 min) labeled analog of DPN to improve signal intensity, accuracy, and sensitivity of PET studies of opioid receptors in the brain.