99mTc-labeled-2-arylbenzoxazole derivatives as potential Aβ imaging probes for single-photon emission computed tomography

• Four 99mTc/Re-labeled 2-arylbenzoxazoles displayed affinity to Aβ1–42 aggregates.
• [99mTc]20 displayed excellent plaque labeling on the brain sections of APP/PS1 mice.
• [99mTc]20 displayed moderate uptake and rapid washout from the normal mice brain.

Four neutral 99mTc/Re-labeled 2-arylbenzoxazole derivatives conjugated to bis (aminoethanethiol) (BAT) chelating ligand via a short propoxy spacer were synthesized and evaluated. In vitro binding assay showed that they displayed binding affinities to Aβ1–42 aggregates (Ki = 15.86–393.18 nM). In vitro autoradiography studies further confirmed the high and specific binding of [99mTc]20 to β-amyloid plaques on brain sections of transgenic mice. Biodistribution study of [99mTc]17–20 in normal mice displayed moderate initial brain uptake (0.96–1.55%ID/g at 2 min), and fast washed out from the brain (0.14–0.40%ID/g at 60 min), especially for [99mTc]20 with a brain2min/brain60min ratio of 8.86. Taken together, these preliminary data suggested that [99mTc]20 may be a potential imaging probe for detecting amyloid plaques in the brain.

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