Delving into the Latest Updates on [18F]-F0502B with Synapse

Overview

Basic Info

Drug Type

Diagnostic radiopharmaceuticals

Synonyms

Target

α-synuclein

Mechanism

α-synuclein modulators(Synuclein alpha modulators)

Therapeutic Areas

Nervous System DiseasesEndocrinology and Metabolic Disease

Active Indication

Parkinson Disease

Inactive Indication-

Originator Organization

The Shenzhen Institutes of Advanced Technology

Active Organization

The Shenzhen Institutes of Advanced Technology

Inactive Organization-

Drug Highest PhasePreclinical

First Approval Date-

Regulation-

Author: Li, Bowei ; Li, Dan ; Liu, Xia ; Xia, Yiyuan ; Bu, Lihong ; Xie, Fang ; Sun, Yunpeng ; Yang, Jenny J ; Liu, Cong ; Xia, Wencheng ; Tao, Youqi ; Zhang, Zhentao ; Kang, Seong Su ; Ye, Keqiang ; Xiang, Jie ; Wang, Xiaochuan ; Guan, Yihui ; Zhang, Mingming ; Luo, Shilin ; Zhao, Qinyue ; Zhang, Xiaoqian ; Cao, Xuebing ; Ahn, Eun-Hee ; Wu, Shengxi

Synucleinopathies are characterized by the accumulation of α-synuclein (α-Syn) aggregates in the brain. Positron emission tomography (PET) imaging of synucleinopathies requires radiopharmaceuticals that selectively bind α-Syn deposits. We report the identification of a brain permeable and rapid washout PET tracer [¹⁸F]-F0502B, which shows high binding affinity for α-Syn, but not for Aβ or Tau fibrils, and preferential binding to α-Syn aggregates in the brain sections. Employing several cycles of counter screenings with in vitro fibrils, intraneuronal aggregates, and neurodegenerative disease brain sections from several mice models and human subjects, [¹⁸F]-F0502B images α-Syn deposits in the brains of mouse and non-human primate PD models. We further determined the atomic structure of the α-Syn fibril-F0502B complex by cryo-EM and revealed parallel diagonal stacking of F0502B on the fibril surface through an intense noncovalent bonding network via inter-ligand interactions. Therefore, [¹⁸F]-F0502B is a promising lead compound for imaging aggregated α-Syn in synucleinopathies.

100 Deals associated with [18F]-F0502B

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