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.
ACS Medicinal Chemistry Letters 4 (5) 436-440
publié le , mis à jour le
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.