PiB-Conjugated, Metal-Based Imaging Probes: Multimodal Approaches for the Visualization of beta-Amyloid Plaques
Abstract
In an effort toward the visualization of beta-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of Afi plaques, to DO3A-monoamide that is capable of forming stable, noncharged complexes with different trivalent metal ions including Gd3+ for MRI and In-111(3+). for SPECT applications. Proton relaxivity measurements evidenced binding of Gd(DO3A-PiB) to the amyloid peptide A beta(1-40) and to human serum albumin, resulting in a two- and four-fold relaidvity increase, respectively.
Ex vivo immunohistochemical studies showed that the DO3A-PiB complexes selectively target A beta plaques on Alzheimer's disease human brain tissue. Ex vivo biodistribution data obtained for the In-111-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.