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.