文摘
In an effort toward the visualization of 尾-amyloid plaques by in vivo imaging techniques, we have conjugated an optimized derivative of the Pittsburgh compound B (PiB), a well-established marker of A尾 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 A尾1鈥?0 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 A尾 plaques on Alzheimer鈥檚 disease human brain tissue. Ex vivo biodistribution data obtained for the 111In-analogue pointed to a moderate blood鈥揵rain barrier (BBB) penetration in adult male Swiss mice (without amyloid deposits) with 0.36% ID/g in the cortex at 2 min postinjection.
Keywords:
imaging agents; Gd3+; 111In3+; amyloid plaques; Alzheimer鈥檚 disease; Pittsburgh compound B