Imaging technology for Neurodegenerative diseases - Progress toward detection of specific pathologies
ABSTRACT Advances in neuroimaging over the past 2 decades are products of breakthroughs in imaging technology, developments of more powerful computers and image-processing software, and expanding knowledge in basic and clinical neuroscience. In addition to the insights into normal brain structure and function that such methods provide and the information that can be gained from disease-related changes in structure and function, the promise of achieving diagnostic specificity through neuroimaging lies with the potential identification of pathognomonic proteins. Recent advances in imaging beta-amyloid plaques, one of the hallmarks of Alzheimer disease, offer such a technological breakthrough and the possibility for more efficient assessment of antiamyloid interventions as well as specific noninvasive diagnostic capabilities.
- SourceAvailable from: Ricardo Maccioni
When Things Go Wrong - Diseases and Disorders of the Human Brain, 02/2012; , ISBN: 978-953-51-0111-6
- "So far, the most successful molecules have been those with a relatively low molecular weight (Figure 2) (Mathis et al., 2005). It has been shown that some benzimidazole and quinoline derivatives tag aggregated forms of tau in vitro and in the context of human brain (Mathis et al., 2005; Okamura et al., 2004; Okamura et al., 2005; Rojo et al., 2007a). This could serve as the milestone for developing neuroimaging technologies to visualize NFTs in the brain of AD patients and those affected with mild cognitive impairments (MCI). "
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- "In this context , several publications have demonstrated that cerebral amyloid aggregates, may not continue to accumulate during AD progress, and thus the amount of SP observed at any time point (including the autopsy) may reflect a competing processes of deposition and resolution of amyloid aggregates . These finding could explain why the PIB-compound and other similar PS-selective technologies are not been widely accepted in the clinical setting as radiotracers for AD, even after almost seven years of its pioneer clinical trial . According to a recent clinical study on PIB imaging , AD diagnosis would be "…possible" but not "probable" and certainly not "definite..." if it is based on SP-selective radiotracers , such as PIB compound and others Fig. (1). "
ABSTRACT: A major limitation in finding therapeutic solutions for Alzheimer's disease (AD) has been the lack of a reliable method for early diagnosis of this devastating disease. Besides the development of biomarkers in biological fluids of patients, the search for a pathology-specific neuroimaging tools is critical at the present stage in which almost 30 million people suffer this disease worldwide. Several interesting approaches have been developed, however their clinical impact has been low. One of the difficulties has been to find the proper molecular tracers to specifically tag pathognomonic lesions in AD brain, including not only amyloid aggregates but also filaments of the modified microtubule-associated protein tau. In this review, we analyze the evidence towards developing pathology-specific diagnostic tools for AD. We analyze the current evidence and clinical implications of new imaging technologies for AD, and how tau hypothesis and the amyloid cascade hypothesis will impact on these scientific efforts in the near future.Current Alzheimer research 05/2011; 8(6):652-8. DOI:10.2174/156720511796717203 · 3.80 Impact Factor
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- "Recent success in developing radionuclide-labeled agents targeting the Ab aggregates provides a window of opportunity to improve the diagnosis of AD (Klunk et al., 2004; Mathis et al., 2005). Positron emission tomography (PET), a common nuclear imaging modality, can provide functional information on the pathophysiological processes of AD. "
ABSTRACT: We report herein the Good Manufacturing Practice (GMP)-compliant automated synthesis of (18)F-labeled styrylpyridine, AV-45 (Florbetapir), a novel tracer for positron emission tomography (PET) imaging of beta-amyloid (Abeta) plaques in the brain of Alzheimer's disease patients. [(18)F]AV-45 was prepared in 105 min using a tosylate precursor with Sumitomo modules for radiosynthesis under GMP-compliant conditions. The overall yield was 25.4+/-7.7% with a final radiochemical purity of 95.3+/-2.2% (n=19). The specific activity of [(18)F]AV-45 reached as high as 470+/-135 TBq/mmol (n=19). The present studies show that [(18)F]AV-45 can be manufactured under GMP-compliant conditions and could be widely available for routine clinical use.Applied radiation and isotopes: including data, instrumentation and methods for use in agriculture, industry and medicine 12/2010; 68(12):2293-7. DOI:10.1016/j.apradiso.2010.07.001 · 1.06 Impact Factor