Radioisotopes Research Today is a free monthly online journal that collates and summarizes the latest research about Radioisotopes, including details on radioimmunotherapy, radionuclides, procedures, hazards. | ||||||||
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Radioiodinated clioquinol as a biomarker for beta-amyloid: Zn complexes in Alzheimer's disease.Opazo C, Luza S, Villemagne VL, Volitakis I, Rowe C, Barnham KJ, Strozyk D, Masters CL, Cherny RA, Bush AI Oxidation Disorders Laboratory, Mental Health Research Institute of Victoria, and Department of Pathology, the University of Melbourne, Parkville, Victoria, Australia. Neocortical beta-amyloid (Abeta) aggregates in Alzheimer's disease (AD) are enriched in transition metals that mediate assembly. Clioquinol (CQ) targets metal interaction with Abeta and inhibits amyloid pathology in transgenic mice. Here, we investigated the binding properties of radioiodinated CQ ([(125)I]CQ) to different in vitro and in vivo Alzheimer models. We observed saturable binding of [(125)I]CQ to synthetic Abeta precipitated by Zn(2+) (K(d)=0.45 and 1.40 nm for Abeta(1-42) and Abeta(1-40), respectively), which was fully displaced by free Zn(2+), Cu(2+), the chelator DTPA (diethylene triamine pentaacetic acid) and partially by Congo red. Sucrose density gradient of post-mortem AD brain indicated that [(125)I]CQ concentrated in a fraction enriched for both Abeta and Zn, which was modulated by exogenous addition of Zn(2+) or DTPA. APP transgenic (Tg2576) mice injected with [(125)I]CQ exhibited higher brain retention of tracer compared to non-Tg mice. Autoradiography of brain sections of these animals confirmed selective [(125)I]CQ enrichment in the neocortex. Histologically, both thioflavine-S (ThS)-positive and negative structures were labeled by [(125)I]CQ. A pilot SPECT study of [(123)I]CQ showed limited uptake of the tracer into the brain, which did however, appear to be more rapid in AD patients compared to age-matched controls. These data support metallated Abeta species as the neuropharmacological target of CQ and indicate that this drug class may have potential as in vivo imaging agents for Alzheimer neuropathology. Published 30 January 2006 in Aging Cell, 5(1): 69-79.
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