Molecular Imaging of Alzheimer’s Disease-Related Sigma-1 Receptor in the Brain <b><i>via</i></b> a Novel Ru-Mediated Aromatic <sup><b>18</b></sup>F-deoxyfluorination Probe
Ping Bai, Frederick A. Bagdasarian, Yulong Xu, Yanli Wang, Yongle Wang, Ashley Gomm, Yanting Zhou, Rui Wu, Hsiao‐Ying Wey, Rudolph E. Tanzi, Can Zhang, Yu Lan, Changning Wang
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.