Synthesis and Characterization of Novel Radioiodinated Triazole-Pyrolidine Derivative to Detect Orexin 2 Receptor in the Brain

Abstract

It is generally accepted that the orexin 2 receptor (OX₂R) plays a critical role in the arousal-promoting function, and in vivo imaging of OX₂R is expected to contribute to elucidation of orexin systems and the development of drugs to treat sleep disorder. In this study, we newly synthesized and characterized a radioiodinated triazole-pyrolidine derivative ([¹²⁵I]TPI) to detect OX₂R in the brain. In vitro studies using OX₁R or OX₂R expression cells showed selective binding of [¹²⁵I]TPI to OX₂R. In addition, in vitro autoradiography using rat brain sections showed high accumulation of radioactivity in the OX₂R expression region. However, [¹²⁵I]TPI showed low brain uptake in normal mice. These results suggest that [¹²⁵I]TPI has a fundamental character to detect OX₂R in vitro, but further structural modification to improve brain pharmacokinetics is required to use it for in vivo detection of OX₂R.