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

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 well-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 Gd­(DO3A-PiB) to the amyloid peptide Aβ_1–40 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 Alzheimer’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