Showing papers by "F. Van Leuven published in 2009"

Synthesis and evaluation of two fluorine-18 labelled phenylbenzothiazoles as potential in vivo tracers for amyloid plaque imaging

Abstract: Uncharged derivatives of thioflavin-T have known in vitro and in vivo affinity for amyloid β. We synthesized and evaluated two derivatives with a fluorine-18 labelled fluoropropoxy substituent either at the 6-position or at the 2′-position of the 2-(4′-aminophenyl)-1,3-benzothiazole core with the aim to get suitable radiotracers to perform amyloid plaque imaging. The fluorine-18 labelled compounds were obtained by nucleophilic substitution of the corresponding tosyl precursors with [18F]fluoride with a radiochemical yield of 50%, yielding 6-(3′′-[18F]fluoropropoxy)-2-(4′-aminophenyl)-1,3-benzothiazole ([18F]2) and 2-[2′-(3′′-[18F]fluoropropoxy)-4′-aminophenyl]-1,3-benzothiazole ([18F]3) with a specific activity between 33 and 51 GBq/µmol. The identity of the radiolabelled compounds was confirmed using radio-LC-MS and by comparing retention times on RP-HPLC. Biodistribution studies in healthy mice showed for both compounds a relatively high initial brain uptake, which was significantly higher for [18F]2 than for [18F]3 (4.5% ID/g versus 3.0% ID/g, p<0.05). Wash-out from control brain was faster for [18F]3. In vitro binding affinity tests using human AD brain homogenates revealed that only compound 2 has affinity for fibrillar amyloid β (Ki=14.5 nM). This was confirmed by the incubation of transgenic APP mouse brain sections with the cold compounds, where 3 did not stain any structure whereas 2 stained amyloid plaques present in APP mouse brain. These data suggest that [18F]2 may be a useful tracer for in vivo visualization of fibrillar amyloid β. Copyright © 2009 John Wiley & Sons, Ltd.