PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of 尾-Amyloid Plaques

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• 作者：Andr茅 F. Martins ; Jean-Fran莽ois Morfin ; Anna Kub铆膷kov谩 ; Vojt臎ch Kub铆膷ek ; Fr茅d茅ric Buron ; Franck Suzenet ; Milena Salerno ; Adina N. Lazar ; Charles Duyckaerts ; Nicolas Arlicot ; Denis Guilloteau ; Carlos F. G. C. Geraldes ; 脡va T贸th
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2013
• 出版时间：May 9, 2013
• 年：2013
• 卷：4
• 期：5
• 页码：436-440
• 全文大小：289K
• 年卷期：v.4,no.5(May 9, 2013)
• ISSN：1948-5875

文摘

In an effort toward the visualization of 尾-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of A尾 plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd³⁺ for MRI and ¹¹¹In³⁺ for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide A尾_1鈥?0 and to human serum albumin, resulting in a two- and four-fold relaxivity increase, respectively. Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target A尾 plaques on Alzheimer鈥檚 disease human brain tissue. Ex vivo biodistribution data obtained for the ¹¹¹In-analogue pointed to a moderate blood鈥揵rain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.

Keywords:

imaging agents; Gd³⁺; ¹¹¹In³⁺; amyloid plaques; Alzheimer鈥檚 disease; Pittsburgh compound B