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  • Title: Radioiodinated styrylbenzene derivatives as potential SPECT imaging agents for amyloid plaque detection in Alzheimer's disease.
    Author: Kung MP, Hou C, Zhuang ZP, Skovronsky DM, Zhang B, Gur TL, Trojanowski JQ, Lee VM, Kung HF.
    Journal: J Mol Neurosci; 2002; 19(1-2):7-10. PubMed ID: 12212796.
    Abstract:
    Development of probes for beta-amyloid (A beta) plaques, a critical factor associated with Alzheimer's disease (AD), provides important tools for studying their role in AD. Previously, we reported [125I]IMSB and [125I]ISB as excellent probes for A beta plaque labeling. Despite their exquisite in vitro binding characteristics, low brain uptakes (likely due to two ionizable carboxylic acid groups) limited their potential as in vivo imaging agents. To improve brain penetration, we have successfully prepared a neutral radioiodinated probe [125I]3. The improved probe displayed good binding affinity for A beta aggregates (Ki = 2.0 +/- 0.2 using A beta40 aggregates). In addition, the brominated counterpart displayed fluorescent-staining properties of A beta plaques in postmortem AD brain sections similar to BSB, a fluoroscent probe reported previously. [125I]3 gave excellent plaque labeling by film autoradiography of AD brain sections. Unlike [125I]IMSB (which preferentially detects A beta40 plaques), the improved radioioinated probe, [125I]3, can readily detect plaques containing aggregates of both A beta40 and A beta42. The initial brain uptake of [125I]3 in normal mice at 2 min p.i. was moderate (0.18% ID) and displayed a very slow washout from the brain (0.11%.ID at 4 h p.i). Taken together, these data suggest that [125I]3 is useful for in vitro plaque detection, it may not be suitable for in vivo monitoring of A beta progression and deposition.
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