[18F]GTP1 (Genentech Tau Probe 1), a radioligand for detecting neurofibrillary tangle tau pathology in Alzheimer’s disease

Bohórquez, Sandra Sanabria; Mařı́k, Jan; Ogasawara, Annie; Tinianow, Jeff N.; Gill, Herman; Barret, Olivier; Tamagnan, Gilles; Alagille, David; Ayalon, Gai; Manser, Paul T.; Bengtsson, Thomas; Ward, Michael E.; Williams, Simon‐Peter; Kerchner, Geoffrey A.; Seibyl, John; Marek, Kenneth; Weimer, Robby M.

doi:10.1007/s00259-019-04399-0

Cited by 95 publications

(88 citation statements)

References 31 publications

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“…First-generation tau PET ligands all seem to bind mixed 3R/4R paired helical filament (PHF) formations of tau [46][47][48][49][50] [51][52][53]. As these "first-generation" tracers face challenges such as off-target binding, novel tau compounds have been developed, though their relationship with clinical outcome measures has yet to be established in larger cohorts [54,55] [54,[56][57][58][59][60], which have shown reduced off-target binding with similar ontarget signal response [61,62]. As currently available tau PET ligands bind AD-like mixed 3R/4R tau pathology, the utility of tau PET in pure 3R or 4R tauopathies, such as progressive supranuclear palsy and corticobasal degeneration, has shown to be less persuasive [57].…”

Section: Tau Petmentioning

confidence: 99%

Imaging biomarkers in neurodegeneration: current and future practices

et al. 2020

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There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases". In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.

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Section: Tau Petmentioning

confidence: 99%

Imaging biomarkers in neurodegeneration: current and future practices

et al. 2020

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“…For this reason, it was deuterated to improve its in vivo stability to defluorination, which resulted in the development of [ 18 F]GTP1 ( Figure 5). This modification prevented the accumulation of free 18 F-flouride in the skull in clinical PET study, in which it also distinctly differentiated AD subjects from healthy controls [189,192,193].…”

Section: Optimized First Generation Tau Tracersmentioning

confidence: 94%

“…Both preclinical and clinical in vivo kinetic studies showed that the tracer has a good pharmacokinetic profile which allows imaging some minutes earlier than flortaucipir [190,194]. Further investigations however still need to be carried out to properly compare these two tracers [193].…”

Section: Optimized First Generation Tau Tracersmentioning

confidence: 99%

PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape

2020

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Ironically, population aging which is considered a public health success has been accompanied by a myriad of new health challenges, which include neurodegenerative disorders (NDDs), the incidence of which increases proportionally to age. Among them, Alzheimer’s disease (AD) and Parkinson’s disease (PD) are the most common, with the misfolding and the aggregation of proteins being common and causal in the pathogenesis of both diseases. AD is characterized by the presence of hyperphosphorylated τ protein (tau), which is the main component of neurofibrillary tangles (NFTs), and senile plaques the main component of which is β-amyloid peptide aggregates (Aβ). The neuropathological hallmark of PD is α-synuclein aggregates (α-syn), which are present as insoluble fibrils, the primary structural component of Lewy body (LB) and neurites (LN). An increasing number of non-invasive PET examinations have been used for AD, to monitor the pathological progress (hallmarks) of disease. Notwithstanding, still the need for the development of novel detection tools for other proteinopathies still remains. This review, although not exhaustively, looks at the timeline of the development of existing tracers used in the imaging of Aβ and important moments that led to the development of these tracers.

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“…After the development of the initial tau radiotracers discussed above, several pharmaceutical companies started developing and optimizing binding properties, leading to the second-generation of tau radiotracers. Some of these new tracers were based on the structure of existing tracers such as 18F-GTP1 and 18F-PI-2620 [ 75 , 76 ]. 18F-GTP1, a deuterated analog of 18F-T808, was synthesized to reduce the metabolic instability of 18F-T808 by defluorination.…”

Section: 18f-labeled Pet Molecular Probes For Ad Detectionmentioning

confidence: 99%

Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-β Detection

et al. 2020

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Alzheimer’s disease (AD) is the most common form of dementia and results in progressive neurodegeneration. The incidence rate of AD is increasing, creating a major public health issue. AD is characterized by neurofibrillary tangles (NFTs) composed of hyperphosphorylated tau protein and senile plaques composed of amyloid-β (Aβ). Currently, a definitive diagnosis of AD is accomplished post-mortem. Thus, the use of molecular probes that are able to selectively bind to NFTs or Aβ can be valuable tools for the accurate and early diagnosis of AD. The aim of this review is to summarize and highlight fluorinated molecular probes that can be used for molecular imaging to detect either NFTs or Aβ. Specifically, fluorinated molecular probes used in conjunction with 19F MRI, PET, and fluorescence imaging will be explored.

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[18F]GTP1 (Genentech Tau Probe 1), a radioligand for detecting neurofibrillary tangle tau pathology in Alzheimer’s disease

Cited by 95 publications

References 31 publications

Imaging biomarkers in neurodegeneration: current and future practices

Imaging biomarkers in neurodegeneration: current and future practices

PET Radiopharmaceuticals for Alzheimer’s Disease and Parkinson’s Disease Diagnosis, the Current and Future Landscape

Molecular Imaging of Fluorinated Probes for Tau Protein and Amyloid-β Detection

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