Preferred Features of a Fluorine-19 MRI Probe for Amyloid Detection in the Brain

Abstract

Fluorine-19 magnetic resonance imaging (¹⁹F MRI) could be a promising approach for imaging amyloid deposition in the brain. However, the required features of a ¹⁹F MRI probe for amyloid detection remain unclear. In the present study, we investigated a series of compounds as potent ¹⁹F probes that could prevent the reduction in MR signal when bound to amyloid plaques in the brain. Each compound consists of styrylbenzoxazole as a core structure linked by a different length of polyethylene glycol (PEG) chain to one of three types of fluorine-labeled group: a trifluoroethoxy group, a hexafluoroisopropoxy group, or a 3′,5′-bis(trifluoromethyl)benzylamino group. Among these compounds, 6-(3′,6′,9′,15′,18′,21′-heptaoxa-23′,23′,23′-trifluoro tricosanyloxy)-2-(4′-dimethylaminostyryl)benzoxazole [compound 3b (m = 6)], which has a trifluoroethoxy group with seven ethylene glycol groups in the PEG chain, showed significant ¹⁹F MR signals in the brains of AβPPswe/PS1dE9 double-transgenic mice, but not wild-type mice. This suggested that compound 3b (m = 6) could be a useful ¹⁹F MRI probe for amyloid detection. Furthermore, this study identified the most effective length of PEG chain between the fluorine-labeled group and the core structure to ensure a strong MR signal when the probe is bound to amyloid plaques.