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Martins A.F., Morfin J.F., Kubíčková A., Kubíček V., Buron F., Suzenet F., Salerno M., Lazar A.N., Duyckaerts V., Arlicot N., Guilloteau D., Geraldes C.F.G.C. and Tóth E.

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

ACS Medicinal Chemistry Letters 4 (5) 436-440

par Frapart - publié le , mis à jour le

Abstract :

In an effort toward the visualization of β-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a ell-established marker of Aβ 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 d(DO3A-PiB) to the amyloid peptide Aβ1−40 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 Aβ plaques on zheimer’s disease human brain tissue. Ex vivo biodistribution data obtained for the 111In-analogue pointed to a moderate blood−brain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.