First-in-Human PET Imaging of Intranasal Oxytocin: Does the Peptide Actually Reach the Brain?

Six healthy volunteers received intranasal [13N]oxytocin (a radioactively labeled version of oxytocin) and underwent whole-body or head PET/MRI scans. Researchers tracked the peptide's distribution over time using time-activity curves, evaluated uptake in the nasal cavity, trigeminal ganglia, and brain regions, and performed radiation dosimetry analysis. The study was registered on ClinicalTrials.gov (NCT06954650).

Intranasal delivery is widely promoted as a way to get peptides past the blood-brain barrier and into the brain. However, until this study, there was limited direct evidence showing where intranasal oxytocin actually goes in humans. The finding that brain uptake is low and variable challenges assumptions underlying many oxytocin nasal spray studies and highlights the need for better delivery methods.

Intranasal peptide delivery is a hot topic in neuroscience and drug development, with oxytocin being one of the most studied candidates. This first-in-human imaging study provides crucial reality-checking data: while the concept of nose-to-brain delivery is appealing, the actual amount reaching the brain may be far less than assumed. This has implications not only for oxytocin therapeutics but for the entire field of intranasal peptide drug delivery.

The sample size of six participants is very small, limiting generalizability. The short half-life of the 13N radiotracer (approximately 10 minutes) restricted the imaging window and complicated brain uptake assessment. High nasal cavity radioactivity created spillover effects that made precise brain region quantification difficult. Image co-registration between PET and MRI was challenged by these technical limitations. The study only assessed healthy volunteers, not patients with neuropsychiatric conditions.