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Abstract #3041

Camelid single-domain antibodies bioconjugate for the magnetic resonance imaging of Alzheimer’s disease.

Clémence Dudeffant 1, Matthias Vandesquille2, Tengfei Li3, Christelle Ganneau2, Ihsen Youssef3, Benoît Delatour3, Pierre Lafaye4, Sylvie Bay2, and Marc Dhenain1

1Molecular Imaging Research Center (MIRCen), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Fontenay aux Roses, France, 2Unité de Chimie des Biomolécules, Institut Pasteur, Paris, France, 3Institut du cerveau et de la moelle épinière (ICM), Paris, France, 4Plateforme d’Ingénierie des Anticorps, Institut Pasteur, Paris, France

Detection of intracerebral targets with imaging probes is challenging due to the non-permissive nature of blood-brain barrier (BBB). Camelid single-domain antibody-fragments (VHH) are small and stable antibodies able to potentially cross the BBB. Here, we selected VHH specifically targeting amyloid-beta deposits, one of the main lesions of Alzheimer’s disease and labeled them with the contrastophore gadolinium. These innovative contrast agents allowed MRI detection of amyloid deposits in postmortem brain tissues of a mouse model of amyloidosis. The ability to produce VHH conjugates that cross the BBB opens the way for future development of tailored imaging probes targeting intracerebral antigens.

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