TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Largeau, Bérenger; Dupont, Anne-Claire; Guilloteau, Denis; Santiago-Ribeiro, Maria-João; Arlicot, Nicolas

doi:10.1155/2017/6592139

Cited by 38 publications

(47 citation statements)

References 137 publications

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“…115 TSPO PET imaging has been employed as a neuroinflammatory biomarker mainly in the assessment of microglial activities in neurologic diseases. 92,116 A majority of studies have found TSPO had no overlap with glial fibrillary acidic protein (GFAP) maker for astrocytes (another critical player in neuroinflammation), despite a few have demonstrated that TSPO protein co-localized with GFAP. 117,118 This data highlighted that TSPO PET may be interpreted as a biomarker for neuroinflammation due to the combination of microglial and astrocyte activities.…”

Section: Spinal Microglia-neuron Interactions In Acute-to-chronic Paimentioning

confidence: 99%

Spinal microglia-neuron interactions in chronic pain

Chan

et al. 2020

Journal of Leukocyte Biology

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Current deficiency in our understanding of acute-to-chronic pain transition remains a hurdle for developing effective treatments against chronic pain. Whereas neurocentric mechanisms alone are insufficient to provide satisfactory explanation for such transition, neuro-immune crosstalk has attracted attention in recent pain research. In contrast to brain microglia, spinal microglia are activated immediately in various pain states. The fast-responsive enrichment and activation of spinal microglia among different pain conditions have highlighted the crucial role of neuroinflammation caused by microglia-neuron crosstalk in pain initiation. Recent studies have revealed spinal microglia-neuron interactions are also involved in chronic pain maintenance, albeit, with different anatomic distribution, cellular and molecular mechanisms, and biologic functions. Delineating the exact temporal discrepancies of spinal microglia distribution and functions along acute-to-chronic pain transition may provide additional mechanistic insights for drug development to prevent deterioration of acute pain into the chronic state. This narrative review summerizes the longitudinal alterations of spinal microglia-neuron interactions in the initiation of pain hypersensitivity, acuteto-chronic pain progression, and chronic pain maintenance, followed by an overview of current clinical translation of preclinical studies on spinal microglia. This review highlights the crucial role of the interaction between spinal microglia and neighboring neurons in the initiation and maintenance of pain hypersensitivity, in relation to the release of cytokines, chemokines, and neuroactive substances, as well as the modulation of synaptic plasticity. Further exploration of the uncharted functions of spinal microglia-neuron crosstalk may lead to the design of novel drugs for preventing acute-to-chronic pain transition.

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Section: Spinal Microglia-neuron Interactions In Acute-to-chronic Paimentioning

confidence: 99%

Spinal microglia-neuron interactions in chronic pain

Chan

et al. 2020

Journal of Leukocyte Biology

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“…(IC 50 : 14.4 pM) features a 750-fold higher in vitro TSPO binding a nity than DPA-714 (IC 50 : 10.9 nM) [30] . VUIIS1009B (IC 50 : 19.4 pM) features a 560-fold higher in vitro TSPO binding a nity than DPA-714.…”

Section: Introductionmentioning

confidence: 93%

18F-VUIIS1009B Features a Superior Imaging Performance to 18F-DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

Huang¹,

Fan²,

Hao³

et al. 2020

Preprint

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Abstract Purpose Translocator protein (TSPO), an out-mitochondrial membrane protein, is regarded as a key biomarker for neuroinflammation in a variety of neurodegenerative diseases. In this study, we aim to evaluate two highly specific TSPO radiotracers 18F-VUIIS1009A and 18F-VUIIS1009B in a mild cerebral ischemic rat model, and to compare their in vivo performance to the well-established TSPO probe 18F-DPA-714 for neuroinflammation imaging. With multiple graphic analytical methods tested and macro parameters determined, we propose to find a suitable and best quantification method to profile neuroinflammation and measure TSPO density with the three TSPO radiotracers. Methods Cerebral ischemia rat model was created and imaged using 18F-VUIIS1009A, 18F-VUIIS1009B and 18F-DPA-714. Displacement studies using cold analogs were performed to evaluate the binding specificities of 18F-VUIIS1009A and 18F-VUIIS1009B individually. Imaging analysis using arterial plasma input functions (AIFs) was employed to generate Logan plots and parametric images of total distribution volume (VT) for each radiotracer. Reference Logan model using healthy brain as a reference region was introduced to generate parametric images for binding potential (BPND). Results When compared to 18F-DPA-714, 18F-VUIIS1009B demonstrated higher in vitro binding specificity, binding potential (BPND) and distribution volume ratio (DVR). Parameter images of BPND and VT also indicate 18F-VUIIS1009B has a superior imaging profile when compared with other two radiotracers in TSPO imaging. Correlation analysis between BPND for 18F-VUIIS1009B and 18F-DPA-714 also indicates 18F-VUIIS1009B is more sensitive than 18F-DPA-714 in TSPO density measurement. Conclusions This study demonstrates the superiority of 18F-VUIIS1009B to 18F-VUIIS1009A and 18F-DPA-714 in the neuroinflammation imaging. It also demonstrates that 18F-VUIIS1009B PET imaging coupled with parameter mapping (VT and BPND) and graphic analysis holds great promise for neuroinflammation characterization and TSPO density measurement.

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“…Considering this, in this study, for the rst time we evaluated the performance of the highly speci c TSPO radiotracers [ 18 F]VUIIS1009A and [ 18 F]VUIIS1009B with directly comparison to the performance of [ 18 F]DPA-714 in a mild neuroin ammation model. As shown in Figure 1, VUIIS1009A (IC 50 : 14.4 pM) features a 750-fold higher in vitro TSPO binding a nity than DPA-714 (IC 50 : 10.9 nM) [27] . VUIIS1009B (IC 50 : 19.4 pM) features a 560-fold higher in vitro TSPO binding a nity than DPA-714.…”

Section: Introductionmentioning

confidence: 94%

[18F]VUIIS1009B Features a Superior Imaging Performance to [18F]DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

Huang

Ding

Hao

et al. 2020

Preprint

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Purpose: Translocator protein (TSPO), an outer mitochondrial membrane protein, is regarded as a key biomarker for neuroinflammation in a variety of neurodegenerative diseases. In this study, we aim to evaluate two highly specific TSPO radiotracers [18F]VUIIS1009A and [18F]VUIIS1009B in a mild cerebral ischemic rat model, and to compare their in vivo performance to the well-established TSPO probe [18F]DPA-714 for neuroinflammation imaging. With multiple graphic analytical methods tested and macro parameters determined, we propose to find a suitable and best quantification method to profile neuroinflammation and measure TSPO density with the three TSPO radiotracers.Methods: Cerebral ischemia rat model was created and imaged using [18F]VUIIS1009A, [18F]VUIIS1009B and [18F]DPA-714. Displacement studies using non-radioactive analogs were performed to evaluate the binding specificities of [18F]VUIIS1009A and [18F]VUIIS1009B individually. Imaging analysis using arterial plasma input functions (AIFs) was employed to generate Logan plots and parametric images of total distribution volume (VT) for each radiotracer. Reference Logan model using contralateral brain as a reference region was introduced to generate parametric images for binding potential (BPND). Results: When compared to [18F]DPA-714, [18F]VUIIS1009B demonstrated higher binding potential (BPND) and distribution volume ratio (DVR). Parameter images of BPND and VT also indicate [18F]VUIIS1009B has a superior imaging profile with higher BPND and DVR when compared with other two radiotracers in TSPO imaging. Correlation analysis between BPND for [18F]VUIIS1009B and [18F]DPA-714 also indicates [18F]VUIIS1009B is more sensitive than [18F]DPA-714 in TSPO density measurement.Conclusions: This study demonstrates the superiority of [18F]VUIIS1009B to [18F]VUIIS1009A and [18F]DPA-714 in the neuroinflammation imaging. It also demonstrates that [18F]VUIIS1009B PET imaging coupled with parameter mapping (VT and BPND) and graphic analysis using Logan analysis and reference Logan analysis holds great promise for neuroinflammation characterization and TSPO density measurement.

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TSPO PET Imaging: From Microglial Activation to Peripheral Sterile Inflammatory Diseases?

Cited by 38 publications

References 137 publications

Spinal microglia-neuron interactions in chronic pain

Spinal microglia-neuron interactions in chronic pain

18F-VUIIS1009B Features a Superior Imaging Performance to 18F-DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

[18F]VUIIS1009B Features a Superior Imaging Performance to [18F]DPA-714 in TSPO Density Characterization for Neuroinflammatory PET Imaging

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