title: Iodinated tracers for imaging amyloid plaques in the brain.
abstract: Excessive amounts of protein deposits, beta-amyloid (Abeta) plaques, are commonly detected in the postmortem brains of Alzheimer's disease (AD) patients. These Abeta plaques are believed to play an important role in the pathogenesis of the disease. Development of Abeta plaque-specific imaging agents for detecting and monitoring the changes of Abeta plaque deposition in living brains are reported. These agents, if successfully developed, may serve as potential biomarkers for the disease. Several iodinated derivatives based on variety of core structures are labeled with radioiodine as single photon emission computed tomography (SPECT) imaging agents. Thioflavin (or benzothiazole) derivatives displayed excellent in vitro characteristics with high binding affinities for Abeta aggregates (in subnanomolar to nanomolar range) and excellent plaque labeling of AD brain sections. However, the in vivo kinetic properties appeared unfavorable for further development. A novel series of imidazo-pyridine derivative, such as 2-(4'-dimethylaminophenyl)-6-iodo-imidazo[1,2-a]pyridine (IMPY), exhibited highly desirable in vivo properties. Additional structural modification resulting in stilbene derivatives displayed good binding affinities for Abeta aggregates. In addition, fluorene compounds with a rigid tricyclic structure showed in vitro and in vivo characteristics as potential SPECT imaging agents. Criteria for selection of radioiodinated tracers with suitable in vivo properties to detect amyloid plaques are discussed.
authors.affiliation: Departments of Radiology, Pathology and Laboratory Medicine, and Pharmacology, University of Pennsylvania, Philadelphia, PA 19104, USA. kunghf@sunmac.spect.upenn.edu
authors.forename: Hang F
authors.initials: HF
authors.lastname: Kung
authors.forename: Mei Ping
authors.initials: MP
authors.lastname: Kung
authors.forename: Zhi Ping
authors.initials: ZP
authors.lastname: Zhuang
authors.forename: Catherine
authors.initials: C
authors.lastname: Hou
authors.forename: Chi-Wan
authors.initials: CW
authors.lastname: Lee
authors.forename: Karl
authors.initials: K
authors.lastname: Plössl
authors.forename: Bing
authors.initials: B
authors.lastname: Zhuang
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Skovronsky
authors.forename: Virginia M-Y
authors.initials: VM
authors.lastname: Lee
authors.forename: John Q
authors.initials: JQ
authors.lastname: Trojanowski
mesh_terms: D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D058225:Plaque, Amyloid / Q000000981:diagnostic imaging* / Q000378:metabolism; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D016229:Amyloid beta-Peptides; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals