Radioiodinated aza-diphenylacetylenes as potential SPECT imaging agents for beta-amyloid plaque detection.
Two new iodinated fluoro- and hydroxy-pegylated aza-diphenylacetylene derivatives, 1 and 2, targeting beta-amyloid (Abeta) plaques have been successfully prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [(125)I]IMPY (6-iodo-2-(4'-dimethylamino)phenyl-imidazo[1,2-a]pyridine) as the radioligand indicated good binding affinities (K(i)=9.2 and 16.8 nM for 1 and 2, respectively). Brain penetrations of the corresponding radioiodinated ligands, evaluated in the normal mice, showed good initial brain penetrations (3.55% and 5.67% ID/g for [(125)I]1 and [(125)I]2 at 2 min post-injection). The washout from normal mice brain was relatively fast (0.33% and 0.91% ID/g at 2h post-injection). The specific binding of these radioiodinated ligands to beta-amyloid plaques was clearly demonstrated using film autoradiography of AD brain sections. Taken together, these preliminary results strongly suggest that these novel iodinated aza-diphenylacetylenes may be potentially useful for imaging Abeta plaques in the living human brain.
Qu
Wenchao
W
Department of Radiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
Kung
Mei-Ping
MP
Hou
Catherine
C
Jin
Lee-Way
LW
Kung
Hank F
HF
D000114:Acetylene / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D006801:Humans; D007457:Iodine Radioisotopes / Q000494:pharmacology*; D007700:Kinetics; D008024:Ligands; D051379:Mice; D008956:Models, Chemical; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon / Q000295:instrumentation* / Q000379:methods
D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D008024:Ligands; C044735:biphenylacetylene; D000114:Acetylene