Chien, D. T. et al. Early clinical PET imaging results with the novel PHF-tau radioligand [F-18]-T807. J. Alzheimers Dis. 34, 457-468
Siemens Molecular Imaging, Inc., Culver City, CA, USA.Journal of Alzheimer's disease: JAD (Impact Factor: 4.15). 12/2012; 34(2). DOI: 10.3233/JAD-122059
Aggregates of hyperphosphorylated tau (PHF-tau), such as neurofibrillary tangles, are linked to the degree of cognitive impairment in Alzheimer's disease. We have developed a novel PHF-tau targeting positron emission tomography imaging agent, [F-18]-T807, which may be useful for imaging Alzheimer's disease and other tauopathies. Here, we describe the first human brain images with [F-18]-T807.
- "Imaging of tau pathology has lagged behind, but that is changing, with the development of long-awaited PET ligands for in vivo detection of tau deposition. At the symposium , K.A.J. described a work using a newly developed tau- PET ligand [(18)F]-T807  . "
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- "As mentioned before, in AD, there are higher cortical concentrations of Ab than PHF tau. Although in vitro reports have already shown that based on affinity alone, a 3-to 30-fold selectivity for PHF tau is attainable      , simulation studies estimate that a 20-to 50-fold selectivity for PHF tau over Ab will be required to image PHF tau in vivo . In addition to the initial assessment of safety, brain kinetics, and tracer metabolism, the evaluation of tau tracer selectivity in vivo poses some challenges. "
ABSTRACT: The military conflicts of the last decade have highlighted the growing problem of traumatic brain injury in combatants returning from the battlefield. The considerable evidence pointing at the accumulation of tau aggregates and its recognition as a risk factor in neurodegenerative conditions such as Alzheimer's disease have led to a major effort to develop selective tau ligands that would allow research into the physiopathologic underpinnings of traumatic brain injury and chronic traumatic encephalopathy in military personnel and the civilian population. These tracers will allow new insights into tau pathology in the human brain, facilitating research into causes, diagnosis, and treatment of traumatic encephalopathy and major neurodegenerative dementias, such as Alzheimer's disease and some variants of frontotemporal lobar degeneration, in which tau plays a role. The field of selective tau imaging has to overcome several obstacles, some of them associated with the idiosyncrasies of tau aggregation and others related to radiotracer design. A worldwide effort has focused on the development of imaging agents that will allow selective tau imaging in vivo. Recent progress in the development of these tracers is enabling the noninvasive assessment of the extent of tau pathology in the brain, eventually allowing the quantification of changes in tau pathology over time and its relation to cognitive performance, brain volumetrics, and other biomarkers, as well as assessment of efficacy and patient recruitment for antitau therapeutic trials.
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- "[18 F]T807 and [18 F]T808 probes show promising results for tracking tau pathology in early clinical studies. In addition, post-mortem autoradiography followed by immunohistochemistry shows co-localization between these radiopharmaceuticals and phospo-tau antibodies [30,31]. "
ABSTRACT: Hypherphosphorylation of the tau protein leading to the formation of neurofibrillary tangles (NFTs) is a common feature in a wide range of neurodegenerative diseases known as tauopathies, which include Alzheimer's disease (AD) and the frontotemporal dementias (FTDs). Although heavily investigated, the mechanisms underlying the pathogenesis and progression of tauopathies has yet to be fully understood. In this context, several rodent models have been developed that successfully recapitulate the behavioral and neurochemical features of tau pathology, aiming to achieve a better understanding of the link between tau and neurodegeneration. To date, behavioral and biochemical parameters assessed using these models have been conducted using a combination of memory tasks and invasive methods such as cerebrospinal fluid (CSF) sampling or post-mortem analysis. Recently, several novel positron emission tomography (PET) radiopharmaceuticals targeting tau tangles have been developed, allowing for non-invasive in vivo quantification of tau pathology. Combined with tau transgenic models and microPET, these tracers hold the promise of advancing the development of theoretical models and advancing our understanding of the natural history of AD and non-AD tauopathies. In this review, we briefly describe some of the most important insights for understanding the biological basis of tau pathology, and shed light on the opportunity for improved modeling of tau pathology using a combination of tau-radiopharmaceuticals and animal models.
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