# Development and characterisation of novel oxytocin analogues for PET imaging

## TL;DR

This paper introduces a new PET imaging tool to study the oxytocin receptor system, which could help develop therapies for socioemotional disorders.

## Contribution

The authors developed and validated a novel PET radiotracer, [18F]dOTK8[SFB], for in vivo imaging of the oxytocin receptor system.

## Key findings

- [18F]dOTK8[SFB] showed specific accumulation in oxytocin receptor-rich tissues in preclinical studies.
- The radiotracer was successfully produced using a microfluidic reaction approach.
- The tracer demonstrated OTR-specificity and potential for human use in mapping oxytocin receptor distribution.

## Abstract

The oxytocin/oxytocin receptor (OT/OTR) signalling system is involved in socioemotional behaviours, garnering interest as a therapeutic target across multiple clinical conditions. Despite its potential, our limited understanding of how to optimally target it and the scarcity of molecular tools for in vivo studies hinder therapeutic development. Molecular imaging techniques, such as Positron Emission Tomography (PET), can bridge this gap by furnishing direct insights into ligand biodistribution, receptor visualisation and ligand-receptor engagement. Here, we report the design, synthesis and biochemical and pharmacological characterisation of five OT-like peptides as novel PET tracers for investigating the OT/OTR signalling system. dOTK8[SFB] emerged as the most promising OT-like lead. The radioactive version [18F]dOTK8[SFB] was produced using a microfluidic reaction approach and validated by preclinical PET imaging of healthy rats after intravenous ligand administration. [18F]dOTK8[SFB] exhibited specific accumulation in OTR-rich tissues, affirming OTR-specificity and suitability as a new OT-like PET radiotracer for investigating OT/OTR biodistribution in humans.

The oxytocin/oxytocin receptor (OT/OTR) signalling system is a promising therapeutic target for socioemotional disorders, yet its clinical potential is limited by a lack of in vivo molecular tools. Here, the authors develop and validate [18F]dOTK8[SFB] as a PET radiotracer, demonstrating its specificity and potential for in vivo mapping OT/OTR biodistribution.