Synthesis and amyloid binding properties of rhenium complexes: preliminary progress toward a reagent for SPECT imaging of Alzheimer's disease brain.
The definitive diagnosis of Alzheimer's disease (AD) requires the detection of amyloid plaques in postmortem brain. Although the amount of fibrillar amyloid roughly correlates with the severity of symptoms at the time of death, the temporal relationship between amyloid deposition, neuronal loss, and cognitive decline is unclear. To elucidate this relationship, a noninvasive, practical method for the quantitation of brain amyloid deposition is required. We describe herein the initial stages of a strategy to accomplish this goal by single photon computed tomographic imaging. The amyloid-binding dye Congo Red was modified to allow its conjugation to the monoamine-monoamide bis(thiol) ligand. This ligand complexes technetium(V) in its neutral oxo form. A biphenyl-containing building block was conjugated to the protected ligand, and the product was coupled to the relevant aromatic compounds. Rhenium oxo complexes, which are isosteric, but nonradioactive, analogues of the potential imaging agent technetium oxo complexes, were synthesized. These complexes bound to Abeta amyloid fibrils produced in vitro and stained amyloid plaques and vascular amyloid in AD brain sections.
Zhen
W
W
Center for Neurologic Diseases, Brigham and Women's Hospital and Harvard Medical School, Harvard Institutes of Medicine, Room 754, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Han
H
H
Anguiano
M
M
Lemere
C A
CA
Cho
C G
CG
Lansbury
P T
PT
D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D004396:Coloring Agents / Q000378:metabolism; D003224:Congo Red / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000378:metabolism; D015609:Organotechnetium Compounds / Q000138:chemical synthesis / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism*; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000378:metabolism; D012211:Rhenium; D013194:Staining and Labeling; D015899:Tomography, Emission-Computed, Single-Photon
D016229:Amyloid beta-Peptides; D004396:Coloring Agents; D009942:Organometallic Compounds; D015609:Organotechnetium Compounds; D010446:Peptide Fragments; D019275:Radiopharmaceuticals; C078592:amyloid beta-protein (1-40); D003224:Congo Red; D012211:Rhenium