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Oxorhenium(V) and Oxotechnetium(V) Complexes of NS Tetradentate Ligands with a Styrylpyridyl Functional Group: Toward Imaging Agents to Assist in the Diagnosis of Alzheimer's Disease. | LitMetric

AI Article Synopsis

  • - Alzheimer's disease is characterized by amyloid plaques in the brain, primarily made up of aggregated amyloid-β (Aβ), which can potentially be diagnosed using technetium-99m labeled molecules that target these plaques and cross the blood-brain barrier (BBB).
  • - The study involved creating new ligands that bind to amyloid plaques and forming stable complexes with technetium and rhenium, with some having their structures confirmed through X-ray crystallography.
  • - While these complexes could cross the BBB, the research indicated that the brain uptake was insufficient for effective diagnosis of Alzheimer's, leading to the conclusion that further investigation of these specific complexes may not be warranted.

Article Abstract

Alzheimer's disease (AD) is associated with the presence of amyloid plaques in the brain mainly comprised of aggregated forms of amyloid-β (Aβ). Molecules radiolabeled with technetium-99m that cross the blood-brain barrier (BBB) and selectively bind to Aβ plaques have the potential to assist in the diagnosis of AD using single-photon emission computed tomography imaging. In this work, three new tetradentate ligands of pyridyl, amide, amine and thiol donors, featuring a styrylpyridyl group that is known to interact with amyloid plaques, were prepared. The new ligands formed charge-neutral and lipophilic complexes with the [Tc═O] and [Re═O] motifs, and two rhenium complexes were characterized by X-ray crystallography. The rhenium(V) complexes interact with synthetic Aβ and amyloid plaques on human brain tissue. Two of the new ligands were radiolabeled with Tc using a kit-based approach, and their biodistribution in wild-type mice was evaluated. The presence of amide donors in the tetradentate ligand increased the stability of the respective [Tc═O] complexes but reduced brain uptake. While the complexes were able to cross the BBB, the degree of uptake in the brain was not sufficient to justify further investigation of these complexes.

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Source
http://dx.doi.org/10.1021/acs.inorgchem.1c01992DOI Listing

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