Novel ¹⁸F-labeled benzoxazole derivatives as potential positron emission tomography probes for imaging of cerebral β-amyloid plaques in alzheimers disease

Two radiofluoro-pegylated phenylbenzoxazole derivatives, 4-(5-(2-(2-(2-[ ¹⁸F]fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N- methylaniline ([ ¹⁸F]24) and 4-(5-(2-(2-(2-[ ¹⁸F] fluoroethoxy)ethoxy)ethoxy)benzo[d]oxazol-2-yl)-N,N-dimethylaniline ([ ¹⁸F]32), were synthesized and evaluated as probes for imaging cerebral β-amyloid (Aβ) plaques in living brain tissue by PET. [ ¹⁸F]24 and [ ¹⁸F]32 displayed high affinity for Aβ _1-42 aggregates (K _i = 9.3 and 3.9 nM, respectively). In vitro autoradiography with sections of post-mortem AD brain and transgenic mouse brain confirmed the affinity of these tracers. Initial high uptake into and rapid washout from the brain in normal mice were observed. [ ¹⁸F]24 also displayed excellent binding to Aβ plaques in ex vivo autoradiographic experiments with Tg2576 mice. Furthermore, small-animal PET studies demonstrated significant differences in the clearance profile after the administration of [ ¹⁸F]24 between Tg2576 and wild-type mice. The results suggest [ ¹⁸F]24 to be a useful PET agent for detecting Aβ plaques in the living human brain.