Add time:07/12/2019         Source:sciencedirect.com

3-[18F]Fluoro-2-hydroxypropyl substituted compounds were synthesized and evaluated as novel 18F-labeled PET tracers for imaging Aβ plaque in a living brain. All compounds exhibited high binding affinities toward the synthetic Aβ1–42 aggregate and/or Alzheimer’s disease brain homogenate. In the microPET study with normal mice, the 3-[18F]fluoro-2-hydroxypropyl substituted compounds resulted in fast brain washout by reducing the lipophilicities of the compounds. Intriguingly, (S)-configured PET tracers, (S)-[18F]1b and (S)-[18F]1c, exhibited a 2.8 and 4.0-fold faster brain washout rate at a peak/30 min in the mouse brain than the corresponding (R)-configured PET tracers despite there being no meaningful difference in binding affinities toward Aβ plaque. A further evaluation of (S)-[18F]1c with healthy rhesus monkeys also revealed excellent clearance from the frontal cortex with ratios of 7.0, 16.0, 30.0 and 49.0 at a peak/30, 60, 90, and 120 min, respectively. These results suggest that (S)-[18F]1c may be a potential PET tracer for imaging Aβ plaque in a living brain.

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