Camelid single-domain antibodies: A versatile tool for in vivo imaging of extracellular and intracellular brain targets

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• 作者：Tengfei Li^a ; ^b ; ^c ; ^d ; ^e ; ^f ; ¹ ; ¹ ; Matthias Vandesquille^g ; ^h ; ⁱ ; ^j ; ¹ ; Fani Koukouli^k ; Clé ; mence Dudeffant^b ; ^c ; ^d ; ^e ; ⁱ ; ^j ; Ihsen Youssef^b ; ^c ; ^d ; ^e ; Pascal Lenormand^a ; Christelle Ganneau^g ; ^h ; Uwe Maskos^k ; Christian Czech^l ; Fiona Grueninger^l ; Charles Duyckaerts^b ; ^c ; ^d ; ^e ; Marc Dhenainⁱ ; ^j ; Sylvie Bay^g ; ^h ; Benoî ; t Delatour^b ; ^c ; ^d ; ^e ; Pierre Lafaye^a ; ^{pierre.lafaye@pasteur.fr}
• 关键词：VHH ; Blood-brain barrier ; In vivo imaging ; Alzheimer's disease ; Tau ; Abeta
• 刊名：Journal of Controlled Release
• 出版年：2016
• 出版时间：10 December 2016
• 年：2016
• 卷：243
• 期：Complete
• 页码：1-10
• 全文大小：2444 K
• 卷排序：243

文摘

Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). The present work describes two novel single-domain antibodies (VHHs or nanobodies) that specifically recognize extracellular amyloid deposits and intracellular tau neurofibrillary tangles, the two core lesions of Alzheimer's disease (AD). Following intravenous administration in transgenic mouse models of AD, in vivo real-time two-photon microscopy showed gradual extravasation of the VHHs across the BBB, diffusion in the parenchyma and labeling of amyloid deposits and neurofibrillary tangles. Our results demonstrate that VHHs can be used as specific BBB-permeable probes for both extracellular and intracellular brain targets and suggest new avenues for therapeutic and diagnostic applications in neurology.