Molecular Imaging of Alzheimer’s Disease-Related Sigma-1 Receptor in the Brain <b><i>via</i></b> a Novel Ru-Mediated Aromatic ^<b>18</b>F-deoxyfluorination Probe

Abstract

Sigma-1 receptor (σ 1 R) is an intracellular protein implicated in a spectrum of neurodegenerative conditions, notably Alzheimer’s disease (AD). Positron emission tomography (PET) imaging of brain σ 1 R could provide a powerful tool for better understanding the underlying pathomechanism of σ 1 R in AD. In this study, we successfully developed a 18 F-labeled σ 1 R radiotracer [ 18 F]CNY-05 via an innovative ruthenium (Ru)-mediated 18 F-deoxyfluorination method. [ 18 F]CNY-05 exhibited preferable brain uptake, high specific binding, and slightly reversible pharmacokinetics within the PET scanning time window. PET imaging of [ 18 F]CNY-05 in nonhuman primates (NHP) indicated brain permeability, metabolic stability, and safety. Moreover, autoradiography and PET studies of [ 18 F]CNY-05 in the AD mouse model found a significantly decreased brain uptake compared to that in wild-type mice. Collectively, we have provided a novel 18 F-radiolabeled σ 1 R PET probe, which enables visualizing brain σ 1 R in health and neurological diseases.