P.1.f.019 Methodological aspects of translocator protein positron emission tomography for microglial activation in schizophrenia patients

2015 ◽  
Vol 25 ◽  
pp. S234-S235
Author(s):  
L. De Picker ◽  
S. Staelens ◽  
S. Ceyssens ◽  
J. Verhaeghe ◽  
S. Deleye ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Positron Emission ◽  
Methodological Aspects

scholarly journals From positron emission tomography to cell analysis of the 18-kDa Translocator Protein in mild traumatic brain injury

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Clément Delage ◽  
Nicolas Vignal ◽  
Coralie Guerin ◽  
Toufik Taib ◽  
Clément Barboteau ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Positron Emission Tomography ◽  
Flow Cytometry ◽  
Microglial Activation ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Flow Cytometry Analysis ◽  
Positron Emission ◽  
The Brain ◽  
Tspo Expression

AbstractTraumatic brain injury (TBI) leads to a deleterious neuroinflammation, originating from microglial activation. Monitoring microglial activation is an indispensable step to develop therapeutic strategies for TBI. In this study, we evaluated the use of the 18-kDa translocator protein (TSPO) in positron emission tomography (PET) and cellular analysis to monitor microglial activation in a mild TBI mouse model. TBI was induced on male Swiss mice. PET imaging analysis with [18F]FEPPA, a TSPO radiotracer, was performed at 1, 3 and 7 days post-TBI and flow cytometry analysis on brain at 1 and 3 days post-TBI. PET analysis showed no difference in TSPO expression between non-operated, sham-operated and TBI mice. Flow cytometry analysis demonstrated an increase in TSPO expression in ipsilateral brain 3 days post-TBI, especially in microglia, macrophages, lymphocytes and neutrophils. Moreover, microglia represent only 58.3% of TSPO+ cells in the brain. Our results raise the question of the use of TSPO radiotracer to monitor microglial activation after TBI. More broadly, flow cytometry results point the lack of specificity of TSPO for microglia and imply that microglia contribute to the overall increase in TSPO in the brain after TBI, but is not its only contributor.

scholarly journals The methodology of TSPO imaging with positron emission tomography

2015 ◽  
Vol 43 (4) ◽  
pp. 586-592 ◽  
Author(s):  
Federico E. Turkheimer ◽  
Gaia Rizzo ◽  
Peter S. Bloomfield ◽  
Oliver Howes ◽  
Paolo Zanotti-Fregonara ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Cellular Heterogeneity ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Expected Improvement ◽  
Positron Emission ◽  
Distribution In Blood ◽  
Methodological Aspects ◽  
Tspo Imaging

The 18-kDA translocator protein (TSPO) is consistently elevated in activated microglia of the central nervous system (CNS) in response to a variety of insults as well as neurodegenerative and psychiatric conditions. It is therefore a target of interest for molecular strategies aimed at imaging neuroinflammation in vivo. For more than 20 years, positron emission tomography (PET) has allowed the imaging of TSPO density in brain using [11C]-(R)-PK11195, a radiolabelled-specific antagonist of the TSPO that has demonstrated microglial activation in a large number pathological cohorts. The significant clinical interest in brain immunity as a primary or comorbid factor in illness has sparked great interest in the TSPO as a biomarker and a surprising number of second generation TSPO radiotracers have been developed aimed at improving the quality of TSPO imaging through novel radioligands with higher affinity. However, such major investment has not yet resulted in the expected improvement in image quality. We here review the main methodological aspects of TSPO PET imaging with particular attention to TSPO genetics, cellular heterogeneity of TSPO in brain tissue and TSPO distribution in blood and plasma that need to be considered in the quantification of PET data to avoid spurious results as well as ineffective development and use of these radiotracers.

scholarly journals Depiction of microglial activation in aging and dementia: Positron emission tomography with [11C]DPA713 versus [11C](R)PK11195

2016 ◽  
Vol 37 (3) ◽  
pp. 877-889 ◽  
Author(s):  
Masamichi Yokokura ◽  
Tatsuhiro Terada ◽  
Tomoyasu Bunai ◽  
Kyoko Nakaizumi ◽  
Kiyokazu Takebayashi ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Microglial Activation ◽  
Second Generation ◽  
Neuronal Degeneration ◽  
Brain Regions ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Binding Potential ◽  
Healthy Elderly ◽  
Positron Emission

The presence of activated microglia in the brains of healthy elderly people is a matter of debate. We aimed to clarify the degree of microglial activation in aging and dementia as revealed by different tracers by comparing the binding potential (BPND) in various brain regions using a first-generation translocator protein (TSPO) tracer [11C]( R)PK11195 and a second-generation tracer [11C]DPA713. The BPND levels, estimated using simplified reference tissue models, were compared among healthy young and elderly individuals and patients with Alzheimer’s disease (AD) and were correlated with clinical scores. An analysis of variance showed category-dependent elevation in levels of [11C]DPA713 BPND in all brain regions and showed a significant increase in the AD group, whereas no significant changes among groups were found when [11C]( R)PK11195 BPND was used. Cognito-mnemonic scores were significantly correlated with [11C]DPA713 BPND levels in many brain regions, whereas [11C]( R)PK11195 BPND failed to correlate with the scores. As mentioned elsewhere, the present results confirmed that the second-generation TSPO tracer [11C]DPA713 has a greater sensitivity to TSPO in both aging and neuronal degeneration than [11C]( R)PK11195. Positron emission tomography with [11C]DPA713 is suitable for the delineation of in vivo microglial activation occurring globally over the cerebral cortex irrespective of aging and degeneration.

scholarly journals [18F]FEDAC translocator protein positron emission tomography–computed tomography for early detection of mitochondrial dysfunction secondary to myocardial ischemia

2021 ◽  
Author(s):  
Rui Luo ◽  
Lei Wang ◽  
Fei Ye ◽  
Yan-Rong Wang ◽  
Wei Fang ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Positron Emission Tomography ◽  
Early Detection ◽  
Myocardial Ischemia ◽  
Mitochondrial Dysfunction ◽  
High Performance ◽  
Dynamic Imaging ◽  
Translocator Protein ◽  
Emission Tomography ◽  
Positron Emission

Abstract Background This study aimed to evaluate the biodistribution and kinetics of [18F]FEDAC targeting the translocator protein TSPO in the myocardium, and to explore its use for the identification of mitochondrial dysfunction. We also assessed the feasibility of [18F]FEDAC for the early detection of mitochondrial dysfunction associated with myocardial ischemia (MI). Methods The radiochemical purity and stability of [18F]FEDAC were analyzed by radio-high-performance liquid chromatography (radio-HPLC). Its biodistribution and kinetics were evaluated by dissection and dynamic imaging using micro-positron emission tomography–computed tomography (micro-PET–CT) in healthy mice. [18F]FEDAC was also applied in an MI rat model and in sham-operated controls. Mitochondrial changes were observed by immunohistochemical staining and electron microscopy. Results Radioactivity levels (%ID/g) in the myocardium in normal mice, determined by [18F]FEDAC, were 8.32 ± 0.80 at 5 min and 2.40 ± 0.10 at 60 min. PET showed significantly decreased uptake by injured cardiac tissue in MI rats, with maximal normal-to-ischemic uptake ratios of 10.47 ± 3.03 (1.5 min) and 3.92 ± 1.12 (27.5 min) (P = 0.025). Immunohistochemistry confirmed that TSPO expression was decreased in MI rats. Mitochondrial ultrastructure demonstrated significant swelling and permeability. Conclusion [18F]FEDAC uptake is reduced in the injured myocardium, consistent with mitochondrial dysfunction. These results may provide new evidence to aid the early detection of mitochondrial dysfunction associated with myocardial ischemic injury.

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