Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine

Gulyás, Balázs; Vas, Ádám; Tóth, Miklós; Takano, Akihiro; Varrone, Andrea; Cselényi, Zsolt; Schain, Martin; Mattsson, Patrik; Halldin, Christer

doi:10.1016/j.neuroimage.2011.02.020

Cited by 83 publications

(71 citation statements)

References 92 publications

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“…In this case, quantification was via V T estimated using a metabolite-corrected arterial plasma input function for which, as in the current study, there was a large interindividual variability. In work by Gulyás et al, 40 the SUV of [ 11 C]vinpocetine was found to increase with age in some brain regions, with similar increases found for healthy controls and patients with Alzheimer's disease.…”

Section: Discussionmentioning

confidence: 61%

[¹¹C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

Walker

Dinelle

Kornelsen

et al. 2015

J Cereb Blood Flow Metab

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Neuroinflammation in the aging rat brain was investigated using [11 C]PBR28 microPET (positron emission tomography) imaging. Normal rats were studied alongside LRRK2 p.G2019S transgenic rats; this mutation increases the risk of Parkinson's disease in humans. Seventy [ 11 C]PBR28 PET scans were acquired. Arterial blood sampling enabled tracer kinetic modeling and estimation of V T . In vitro autoradiography was also performed. PBR28 uptake increased with age, without differences between nontransgenic and transgenic rats. In 12 months of aging (4 to 16 months), standard uptake value (SUV) increased by 56% from 0.44 to 0.69 g/mL, whereas V T increased by 91% from 30 to 57 mL/cm 3 . Standard uptake value and V T were strongly correlated (r = 0.52, 95% confidence interval (CI) = 0.31 to 0.69, n = 37). The plasma free fraction, f p , was 0.21 ± 0.03 (mean ± standard deviation, n = 53). In vitro binding increased by 19% in 16 months of aging (4 to 20 months). The SUV was less variable across rats than V T ; coefficients of variation were 13% (n = 27) and 29% (n = 12). The intraclass correlation coefficient for SUV was 0.53, but was effectively zero for V T . These data show that [11 C]PBR28 brain uptake increases with age, implying increased microglial activation in the aged brain.

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Section: Discussionmentioning

confidence: 61%

[¹¹C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

Walker

Dinelle

Kornelsen

et al. 2015

J Cereb Blood Flow Metab

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“…More recently, Schuitemaker et al [128] reported an increase in the specific binding of [ 11 C]PK-11195 with aging in healthy subjects (19-79 years old) in several cortical and subcortical areas (frontal cortex, anterior and posterior cingulate cortex, medial inferior temporal lobe, insula, hippocampus, entorhinal cortex, thalamus, parietal and occipital cortex and cerebellum) [128]. Gulyas et al [164] used PET with [ 11 C]vinpocetine, another TSPO radioligand, to study microglial activation during normal brain aging (healthy volunteers aged between 25 and 78 years) and reported increased uptake and binding with age in the entire brain and in all the brain regions studied. The significance of the age-related increase in [ 11 C]PK-11195-specific binding remains undetermined.…”

Section: Discussionmentioning

confidence: 99%

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Hommet

Mondon²,

Camus³

et al. 2013

Dement Geriatr Cogn Disord

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Background/Aims: Neuroinflammation plays a crucial role in the pathogenesis of Alzheimer's disease (AD). Its relationship with underlying β amyloid deposition remains unclear. In vivo visualization of microglial activation has become possible with the development of molecular imaging ligands when used with positron emission tomography (PET). The translocator protein (TSPO) is upregulated during neuroinflammation. Consequently, targeting TSPO with radiolabeled ligands for PET is an attractive biomarker for neuroinflammation. Methods: A review of the research literature on PET imaging which studied in vivo neuroinflammation in AD subjects and its relationship with amyloid load was performed, including papers published between 2001 and 2012. Results: Six studies were included using either [¹¹C]PK-11195 or another non-TSPO radioligand that binds to the monoaminooxidase B. All the studies evaluated amyloid load with [¹¹C]PIB. Microglial activation and astrocytosis are potentially early phenomena in AD. However, the individual levels of amyloid deposition and microglial activation were not correlated. Conclusion: Noninvasive in vivo molecular imaging to visualize neuroinflammation in AD may contribute to our understanding of the kinetics of neuroinflammation and its relationship to the hallmarks of the disease. Both are important for the development of future therapeutic modalities and for quantifying the efficacy of future disease-modifying treatments.

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“…However, it has yet to be firmly established whether the microglial activation observed corresponds with amyloid or tau distribution or represents an independent pathologic distribution. Further, other clinical studies have failed to differentiate Alzheimer disease patients from age-matched controls (9,10). This disparity indicates the importance of trialing a variety of radiotracers for appropriate sensitivity and specificity.…”

Section: Second-and Third-generation Tspo Radiotracers In Neurologic mentioning

confidence: 99%

Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?

2015

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Neuroinflammation is implicated in the pathogenesis of a wide range of neurologic and neuropsychiatric diseases. For over 20 years, 11 C-PK11195 PET, which aims to image expression of the translocator protein (TSPO) on activated microglia in the brain, has been used in preclinical and clinical research to investigate neuroinflammation in vivo in patients with brain diseases. However, 11 C-PK11195 suffers from two major limitations: its low brain permeability and high nonspecific and plasma binding results in a low signal-to-noise ratio, and the use of 11 C restricts its use to PET research centers and hospitals with an on-site cyclotron. In recent years, there has been a great deal of work into the development of new TSPO-specific PET radiotracers. This work has focused on fluorinated radiotracers, which would enable wider use and improved signal-to-noise ratios. These radiotracers have been utilized in preclinical and clinical studies of several neurologic diseases with varying degrees of success. Unfortunately, the application of these second-generation TSPO radiotracers has revealed additional problems, including a polymorphism that affects TSPO binding. In this review, the developments in TSPO imaging are discussed, and current limitations and suggestions for future directions are explored.

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Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine

Cited by 83 publications

References 92 publications

[¹¹C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

[¹¹C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?

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Age and disease related changes in the translocator protein (TSPO) system in the human brain: Positron emission tomography measurements with [11C]vinpocetine

Cited by 83 publications

References 92 publications

[11C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

[11C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

Neuroinflammation and β Amyloid Deposition in Alzheimer's Disease: In vivo Quantification with Molecular Imaging

Imaging Microglial Activation with TSPO PET: Lighting Up Neurologic Diseases?

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[¹¹C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat

[¹¹C]PBR28 PET Imaging is Sensitive to Neuroinflammation in the Aged Rat