PiB-Conjugated, Metal-Based Imaging Probes: Multimodal
Approaches for the Visualization of β‑Amyloid Plaques
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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 well-established marker of Aβ
plaques, to DO3A-monoamide that is capable of forming stable, noncharged
complexes with different trivalent metal ions including Gd<sup>3+</sup> for MRI and <sup>111</sup>In<sup>3+</sup> for SPECT applications.
Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to
the amyloid peptide Aβ<sub>1–40</sub> 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 <sup>111</sup>In-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