New diphenylacetylenes as probes for positron emission tomographic imaging of amyloid plaques

A series of F-18 fluoropegylated diphenylacetylenes as probes for binding to A beta plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b, 14a, and 14b, displayed high binding affinities in postmortem AD brain homogenates (K-i ranging from 1.2 to 2.9 nM). In vivo biodistribution in normal mice exhibited excellent initial brain penetrations (4.42, 4.55, 5.41, and 6.78% dose/g at 2 min for [F-18]12a, 12b, 14a, and 14b, respectively). [F-18]12b and [F-18]14b, with a longer fluoropegylated unit, that is, n = 3, showed faster brain washout at 30 min postinjection (0.42 and 1.57% dose/g) as compared to the shorter fluoropegylated chain ligands, that is, [F-18]12a and [F-18]14a(1.03 and 3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding signal due to A beta plaques. These preliminary results suggest that the novel diphenylacetylenes may be potentially useful for imaging of A beta plaques in the brain of patients with Alzheimer's disease.