A first‑in‑human PET study showed that when you spray oxytocin into the nose, most of it stays in the nasal cavity and only a small, inconsistent amount reaches the brain. The amount that does get into the brain varies a lot between people and can be affected by things like a stuffy nose.

Oxytocin is a neuropeptide with therapeutic potential for several neuropsychiatric and pain-related disorders. Intranasal delivery is proposed to enable access to the central nervous system via the trigeminal nerve and olfactory nerves, thereby bypassing the blood-brain barrier. However, direct evidence of biodistribution following intranasal administration in humans is limited. This study evaluated the feasibility of imaging oxytocin uptake using a novel PET tracer, [¹³N]oxytocin, in healthy volunteers. Six participants received intranasal [¹³N]oxytocin and underwent whole-body or head PET/MRI scans. High tracer uptake was observed in the nasal cavity within the first 5 min, followed by a decline and systemic absorption. Tracer uptake in the trigeminal ganglia and brain varied between individuals, with no clear dose-dependency. One participant with rhinitis showed altered uptake and clearance patterns. Time-activity curves indicated tracer presence in brain regions 25-45 min post-administration, but image co-registration was challenged by high nasal activity and spillover effects. Radiation dosimetry analysis identified the nasal cavity as the critical organ, limiting allowable doses. Despite detectable presence in some brain regions, [¹³N]oxytocin uptake was low and variable. Intranasal [¹³N]oxytocin administration results in rapid and substantial nasal cavity uptake and detectable, but variable, tracer distribution to trigeminal and brain regions. While this technique offers insight into intranasal peptide delivery, limitations related to variable absorption, short half-life, and image co-registration must be addressed. Accordingly, [¹³N]oxytocin is not presently well suited for central nervous system receptor imaging via intranasal administration. Peripheral receptor imaging after intravenous administration may still be feasible, and further optimisation of tracer chemistry, administration protocols, and imaging strategies is warranted. ClinicalTrials.gov identifier: NCT06955650 (registered May 5, 2025).