Microglial activation in Parkinson’s disease using [18F]-FEPPA

Ghadery, Christine; Koshimori, Yuko; Coakeley, Sarah; Harris, Madeleine; Rusjan, Pablo; Kim, Jinhee; Houle, Sylvain; Strafella, Antonio P.

doi:10.1186/s12974-016-0778-1

Cited by 95 publications

(80 citation statements)

References 44 publications

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“…The recent development of second‐generation radiotracers, such as [ 18 F]‐FEPPA, enables researchers to explore the role of TSPO expression in PD by controlling for genotyping expression. Although Strafella and colleagues could not observe increased tracer uptake in the striatum or in the cortical and subcortical brain regions in patients with PD compared to controls, the combination of the radioligands, [ 18 F] FEPPA and [ 11 C] PIB, a measure of β‐amyloid load, revealed interesting findings. The dual‐tracer PET study detected significantly higher [ 18 F] FEPPA binding in PD patients with cognitive impairment in the frontal and temporal lobe, striatum, precuneus, and dorsolateral prefrontal cortex, when β‐amyloid was present in these brain regions .…”

Section: Molecular Imaging Of Pdmentioning

confidence: 97%

Imaging Markers of Progression in Parkinson's Disease

Strafella

Bohnen

Pavese

et al. 2018

Movement Disord Clin Pract

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Background Parkinson's disease (PD) is the second‐most common neurodegenerative disorder after Alzheimer's disease; however, to date, there is no approved treatment that stops or slows down disease progression. Over the past decades, neuroimaging studies, including molecular imaging and MRI are trying to provide insights into the mechanisms underlying PD. Methods This work utilized a literature review. Results It is now becoming clear that these imaging modalities can provide biomarkers that can objectively detect brain changes related to PD and monitor these changes as the disease progresses, and these biomarkers are required to establish a breakthrough in neuroprotective or disease‐modifying therapeutics. Conclusions Here, we provide a review of recent observations deriving from PET, single‐positron emission tomography, and MRI studies exploring PD and other parkinsonian disorders.

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Section: Molecular Imaging Of Pdmentioning

confidence: 97%

Imaging Markers of Progression in Parkinson's Disease

Strafella

Bohnen

Pavese

et al. 2018

Movement Disord Clin Pract

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“…There was limited success [21][22][23][24], but also failures [25][26][27][28][29][30]. Some failures were due to existing genetic polymorphisms affecting TSPO binding in humans [31][32][33]. While this limitation can be corrected [34][35][36][37], the non-specific role of TSPO in neuroinflammation are more difficult to address [9,38,39], as TSPO is involved in many cellular functions not specific to central inflammation [40][41][42][43][44].…”

Section: Introductionmentioning

confidence: 99%

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

et al. 2019

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Purpose: The P2X7 receptor, an adenosine triphosphate (ATP)-gated purinoreceptor, has emerged as one of the key players in neuroinflammatory processes. Therefore, developing a positron emission tomography (PET) tracer for imaging of P2X7 receptors in vivo presents a promising approach to diagnose, monitor, and study neuroinflammation in a variety of brain disorders. To fulfill the goal of developing a P2X7 PET ligand as a biomarker of neuroinflammation, [ 18 F]JNJ-64413739 has been recently disclosed. Procedures: We evaluated [ 18 F]JNJ-64413739 in a rat model of neuroinflammation induced by an intracerebral injection of lipopolysaccharide (LPS). In vivo brain uptake was determined by PET imaging. Upregulation of neuroinflammatory biomarkers was determined by quantitative polymerase chain reaction (qPCR). Distribution of the tracer in the brain was determined by ex vivo autoradiography (ARG). The specificity of [ 18 F]JNJ-64413739 was confirmed by performing blocking experiments with the P2X7 antagonist JNJ-54175446. Results: Brain regions of rats injected with LPS had a significantly increased uptake (34 % ± 3 % s.e.m., p = 0.036, t test, standardized uptake value measured over the entire scanning period) of [ 18 F]JNJ-64413739 relative to the corresponding brain regions of control animals injected with phosphate-buffered saline (PBS). The uptake in the contralateral regions and cerebellum was not significantly different between the groups of animals. The increase in uptake of [ 18 F]JNJ-64413739 at the LPS-injected site observed by PET imaging was concordant with ex vivo ARG, upregulation of neuroinflammatory biomarkers, and elevated P2X7 expression levels. Conclusions: While further work is needed to study [ 18 F]JNJ-64413739 in other types of neuroinflammation, the current results favorably characterize [ 18 F]JNJ-64413739 as a potential PET tracer of central neuroinflammation.

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“…The amount of activated microglia is proportional to both the number of Lewy bodies found at autopsy (Mackenzie, 2000) and, in transgenic mice, to the amount of α-synuclein and measured loss of dopaminergic neurons (Gao et al, 2011). Prior TSPO PET studies in patients with Parkinson’s disease without dementia have mostly shown positive results (Bartels et al, 2010; Gerhard et al, 2006; Iannaccone et al, 2013; Ouchi et al, 2005), although there have been a small number of negative studies (Bartels et al, 2010; Ghadery et al, 2017). Two studies also found increased TSPO in PDD or DLB (Edison et al, 2013; Iannaccone et al, 2013).…”

Section: Neuroinflammation In Non-alzheimer’s Dementiasmentioning

confidence: 99%

Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

Kreisl

Henter

Innis

2018

Advances in Pharmacology

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Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer’s disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18 kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET). Increased TSPO density has been observed in brain tissue from patients with neurodegenerative diseases and colocalizes to activated microglia and reactive astrocytes. Several radioligands have been developed to measure TSPO density in vivo with PET, and these have been used in clinical studies of different dementia syndromes. However, TSPO radioligands have limitations, including low specific-to-nonspecific signal and differential affinity to a polymorphism on the TSPO gene, which must be taken into consideration in designing and interpreting human PET studies. Nonetheless, most PET studies have shown that increased TSPO binding is associated with various dementias, suggesting that TSPO has potential as a biomarker to further explore the role of neuroinflammation in dementia pathogenesis and may prove useful in monitoring disease progression.

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Microglial activation in Parkinson’s disease using [18F]-FEPPA

Cited by 95 publications

References 44 publications

Imaging Markers of Progression in Parkinson's Disease

Imaging Markers of Progression in Parkinson's Disease

PET Imaging of the P2X7 Ion Channel with a Novel Tracer [18F]JNJ-64413739 in a Rat Model of Neuroinflammation

Imaging Translocator Protein as a Biomarker of Neuroinflammation in Dementia

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