Synthesis and Bioevaluation of 2-Styrylquinoxaline Derivatives as Tau-PET Tracers. Academic Article uri icon

Overview

abstract

  • This study focused on designing and evaluating Tau-PET tracers for noninvasive positron emission computed tomography (PET) imaging of neurofibrillary tangles (NFTs), a hallmark pathology of Alzheimer's disease (AD). The tracers were synthesized with a 2-styrylquinoxaline scaffold and varying lengths of FPEG chains. The compound [18F]15, which had two ethoxy units, showed high affinity for recombinant K18-Tau aggregates (Ki = 41.48 nM) and the highest selectivity versus Aβ1-42 aggregates (8.83-fold). In vitro autoradiography and fluorescent staining profiles further validated the binding of [18F]15 or 15 toward NFTs in brain sections from AD patients and Tau-transgenic mice. In normal ICR mice, [18F]15 exhibited an ideal initial brain uptake (11.21% ID/g at 2 min) and moderate washout ratio (2.29), and micro-PET studies in rats confirmed its ability to penetrate the blood-brain barrier with the peak SUV value of 1.94 in the cortex. These results suggest that [18F]15 has the potential to be developed into a useful Tau-PET tracer for early AD diagnosis and evaluation of anti-Tau therapeutics.

publication date

  • October 18, 2023

Research

keywords

  • Alzheimer Disease
  • tau Proteins

Identity

Scopus Document Identifier

  • 85176495241

Digital Object Identifier (DOI)

  • 10.1021/acs.molpharmaceut.3c00717

PubMed ID

  • 37852240

Additional Document Info

volume

  • 20

issue

  • 11