First-in-man Imaging of a New PET Radiotracer for Oxytocin Receptors

Overview

The investigators will test a new positron-emitting radiotracer to determine whether it is suitable for studying the oxytocin receptor by positron emission tomography (PET) in humans. If suitable, the radiotracer will be used to study the brain and trigeminal nerve in several disorders.

The nine amino acid peptide oxytocin was first isolated in 1927 and is primarily recognised for its hormonal role in uterine contractions, lactation, and social bonding. It has been used to induce labour via infusion since the 1950s and was previously approved for nasal application to aid lactation, although its effectiveness for this purpose has since been questioned. Oxytocin is also involved in the modulation of pain within the body. It has been localised to the human dorsal root and trigeminal ganglia, and the terminals of hypothalamic neurons containing oxytocin-specific carrier proteins have been found in the dorsal horn of the spinal trigeminal nucleus. Oxytocin receptors have been identified in regions of the spinal cord associated with pain transmission in both non-human primates and rodents. Animal studies have provided evidence of oxytocin's analgesic effects, particularly following direct administration into the spinal canal or brain cavities. Intrathecal administration of oxytocin, as opposed to intravenous delivery, has shown effectiveness in reducing chronic low back pain in humans, potentially involving the body's own opioid system. While direct access to the trigeminal system is challenging due to the skull's structure, a promising alternative is the nasocerebral pathway. This pathway enables certain substances administered nasally to reach central nervous system structures and has been explored as a method for delivering treatments to regions affected by neurodegenerative conditions. Preliminary research suggests that intranasal delivery of oxytocin leads to pain relief restricted to areas supplied by the trigeminal nerve in both animals and humans. This effect appears to result from the nasal route enabling oxytocin to reach trigeminal receptors directly. In preclinical models, nasal but not systemic administration produced a significant analgesic effect in the face. Similar outcomes were observed in individuals with chronic migraine, where nasal oxytocin administration led to a strong reduction in facial pain. These findings suggest that intranasal oxytocin may work by concentrating in the trigeminal nerve via the nasocerebral route. The current study aims to evaluate how oxytocin distributed via nasal administration spreads in the body, using positron emission tomography (PET). This imaging technique will allow visualisation of how the compound moves through the body and whether it reaches relevant structures such as the trigeminal nerve. The goal is to better understand how intranasal oxytocin might enable targeted pain relief and potentially support its use in treating conditions related to the trigeminal system.

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