Characterization of radioiodinated ligand binding to amyloid beta plaques.
Several novel series of iodinated compounds based on the thioflavin backbone structure have been developed and characterized. These iodinated compounds showed high specific binding to amyloid beta (Abeta) aggregates with subnanomolar to nanomolar affinities. Probes like IMPY and MIPA display high brain uptakes and fast washout in normal mice, resulting in low background signals (presumably no amyloid plaques present in normal mouse brain), whereas TZDM shows long brain retention in normal mice suggesting high nonspecific in vivo binding. It is likely that tracers, that is, IMPY or MIPA, with desirable in vivo properties, will provide the highest target to non-target ratio; therefore, they are most likely to be successful as imaging agents targeting Abeta plaques in the brain.
D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D052160:Benzothiazoles; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism; D008024:Ligands; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000187:drug effects / Q000378:metabolism; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000473:pathology; D011720:Pyrazoles / Q000378:metabolism; D011725:Pyridines / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
C475859:2-(4'-dimethylaminophenyl)-6-iodobenzothiazole; C473191:6-iodo-2-(4'-dimethylamino-)phenyl-imidazo(1,2-a)pyridine; D016229:Amyloid beta-Peptides; D052160:Benzothiazoles; D007457:Iodine Radioisotopes; D008024:Ligands; C479800:MIPA compound; D010446:Peptide Fragments; D011720:Pyrazoles; D011725:Pyridines; D013844:Thiazoles; C078592:amyloid beta-protein (1-40); C009462:thioflavin T