New diphenylacetylenes as probes for positron emission tomographic imaging of amyloid plaques.
A series of 18F fluoropegylated diphenylacetylenes as probes for binding to Abeta plaques were successfully prepared. These relatively rigid acetylenes, 12a, 12b, 14a, and 14b, displayed high binding affinities in postmortem AD brain homogenates (Ki 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 [18F]12a, 12b, 14a, and 14b, respectively). [18F]12b and [18F]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, [18F]12a and [18F]14a (1.03 and 3.69% dose/g). Autoradiography and homogenate binding confirmed the high binding signal due to Abeta plaques. These preliminary results suggest that the novel diphenylacetylenes may be potentially useful for imaging of Abeta plaques in the brain of patients with Alzheimer's disease.
Chandra
Rajesh
R
Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Oya
Shunichi
S
Kung
Mei-Ping
MP
Hou
Catherine
C
Jin
Lee-Way
LW
Kung
Hank F
HF
D000114:Acetylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D005462:Fluorine Radioisotopes; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D058225:Plaque, Amyloid / Q000378:metabolism*; D049268:Positron-Emission Tomography; D011869:Radioligand Assay; D019275:Radiopharmaceuticals / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D014018:Tissue Distribution
D005462:Fluorine Radioisotopes; D019275:Radiopharmaceuticals; D000114:Acetylene