Article

Advances in molecular imaging for the diagnosis of dementia.

Tohoku University, Pharmacology, Sendai, Japan.
Expert Opinion on Medical Diagnostics 11/2009; 3(6):705-16. DOI: 10.1517/17530050903133790
Source: PubMed

ABSTRACT Background: There is an urgent need for early diagnosis and treatment of dementia to ease caregiver burden and medical costs associated with the increasing number of affected patients. Molecular imaging with target-specific ligands is contributing to the early diagnosis of dementia and the evaluation of anti-dementia therapy. Objective: This article reviews recent advances in the molecular imaging field applied to dementia. To illustrate the utility of molecular imaging in the clinical management of dementia, results from recently published papers using new imaging probes are compared with those from conventional imaging strategies. Conclusion: The recent development of β-sheet binding agents including FDDNP, PIB, SB-13, BF-227 and BAY94-9172 enables the non-invasive detection of amyloid deposition in the brain. These agents would be useful for the early and accurate diagnosis of Alzheimer's disease, patient selection for disease-modifying therapeutic trials and monitoring the effect of anti-amyloid therapy. Also, monitoring neurotransmitter function contributes to the differential diagnosis of dementia and refinement of treatment protocols. New targets for molecular imaging are focusing on protein misfolding diseases associated with the neurotoxic deposition of aggregated tau, α-synuclein and prion proteins.

0 Bookmarks
 · 
49 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Hereditary frontotemporal dementia (FTD) associated with mutations in the Microtubule Associated Protein Tau gene (MAPT) is a protean disorder. Three neuropathologic subtypes can be recognized, based on the presence of inclusions made of tau isoforms with 3 and 4 repeats, predominantly 3 repeats and mostly 4 repeats. This is relevant for establishing a correlation between structural magnetic resonance imaging and positron emission tomography using tracers specific for aggregated tau. Longitudinal studies will be essential to determine the evolution of anatomical alterations from the asymptomatic stage to the various phases of disease following the onset of symptoms.
    Neuropathology and Applied Neurobiology 12/2014; DOI:10.1111/nan.12213 · 4.84 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Alzheimer's disease is the most common form of age-related neurodegenerative dementia. The disease is characterised by the presence of plaques in the cerebral cortex. The major constituent of these plaques is aggregated amyloid-β peptide. This review focuses on the molecular aspects of metal complexes designed to bind to amyloid-β. The development of radioactive metal-based complexes of copper and technetium designed as diagnostic imaging agents to detect amyloid burden in the brain is discussed. Separate sections of the review discuss the use of luminescent metal complexes to act as non-conventional probes of amyloid formation and recent research into the use of metal complexes as inhibitors of amyloid formation and toxicity.
    Chemical Society Reviews 03/2014; 43(19). DOI:10.1039/c4cs00026a · 30.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: The aims of this study were to evaluate the binding and pharmacokinetics of novel (18)F-labeled ethenyl-benzoxazole derivatives (i.e., [(18)F] fluorinated amyloid imaging compound of Tohoku university ([(18)F]FACT)) as amyloid positron emission tomography (PET) tracers and to assess [(18)F]FACT efficacy in imaging of Alzheimer's disease (AD). PROCEDURES: Binding assay was conducted using synthetic amyloid-β (Aβ) fibrils, fluorescence microscopy, and autoradiogram in three postmortem AD brains. Pharmacokinetics of [(18)F]FACT was assessed using 12 Crj:CD-1 (ICR) mice. In vivo binding ability with brain amyloid was investigated using amyloid precursor protein (APP) transgenic mouse. Clinical PET scanning using [(18)F]FACT was performed in ten healthy controls and ten mild cognitive impairment and ten AD patients. RESULTS: [(18)F]FACT showed high binding affinity for synthetic Aβ fibrils, preferential binding to dense cored plaques in brain sections, and excellent brain uptake and rapid clearance in mice. Injection in APP mice resulted in specific in vivo labeling of amyloid deposits in the brain. PET scans of AD patients showed significantly higher [(18)F]FACT uptake in the neocortex compared to controls (P < 0.05, Kruskal-Wallis test). CONCLUSION: [(18)F]FACT is a promising agent for imaging dense Aβ plaques in AD.
    Molecular imaging and biology: MIB: the official publication of the Academy of Molecular Imaging 01/2013; DOI:10.1007/s11307-012-0608-5 · 2.47 Impact Factor