Assessment of Neuroinflammation in Transferred EAE Via a Translocator Protein Ligand

Mattner, Filomena; Staykova, Maria; Callaghan, Paul D.; Berghofer, Paula; Ballantyne, Patrice; Grégoire, Marie Claude; Fordham, Susan A.; Pham, Tien; Rahardjo, Gita; Jackson, Timothy; Liñares, David; Katsifis, Andrew

doi:10.5772/31310

Cited by 3 publications

(6 citation statements)

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“…In vitro and in vivo analyses with the SPECT TSPO ligand 123 I-CLINDE (26)(27)(28) confirmed literature data indicating that the TSPO is expressed during neuroinflammation (14) and indicated that 123 I-CLINDE is a sensitive and specific tracer of astroglial activation.…”

Section: Discussionsupporting

confidence: 56%

“…In previous work, we monitored TSPO expression in rats with monophasic EAE induced by myelin basic protein-CFA (26) and transferred EAE induced by myelin basic protein-specific T lymphoblasts (27) as well as in a model of demyelination induced by cuprizone (28). In vitro and in vivo analyses with the SPECT TSPO ligand 123 I-CLINDE (26)(27)(28) confirmed literature data indicating that the TSPO is expressed during neuroinflammation (14) and indicated that 123 I-CLINDE is a sensitive and specific tracer of astroglial activation.…”

Section: Discussionmentioning

confidence: 99%

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Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

et al. 2013

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Glial neuroinflammation is associated with the development and progression of multiple sclerosis. PET imaging offers a unique opportunity to evaluate neuroinflammatory processes longitudinally in a noninvasive and clinically translational manner. 18 F-PBR111 is a newly developed PET radiopharmaceutical with high affinity and selectivity for the translocator protein (TSPO), expressed on activated glia. This study aimed to investigate neuroinflammation at different phases of relapsing-remitting (RR) experimental autoimmune encephalomyelitis (EAE) in the brains of SJL/J mice by postmortem histologic analysis and in vivo by PET imaging with 18 F-PBR111. Methods: RR EAE was induced by immunization with PLP 139-151 peptide in complete Freund's adjuvant. Naive female SJL/J mice and mice immunized with saline-complete Freund's adjuvant were used as controls. The biodistribution of 18 F-PBR111 was measured in 13 areas of the central nervous system and compared with PET imaging results during different phases of RR EAE. The extents of TSPO expression and glial activation were assessed with immunohistochemistry, immunofluorescence, and a real-time polymerase chain reaction. Results: There was significant TSPO expression in all of the central nervous system areas studied at the peak of the first clinical episode and, importantly, at the preclinical stage. In contrast, only a few TSPO-positive cells were observed at the second episode. At the third episode, there was again an increase in TSPO expression. TSPO expression was associated with microglial cells or macrophages without obvious astrocyte labeling. The dynamics of 18 F-PBR111 uptake in the brain, as measured by in vivo PET imaging and biodistribution, followed the pattern of TSPO expression during RR EAE. Conclusion: PET imaging with the TSPO ligand 18 F-PBR111 clearly reflected the dynamics of microglial activation in the SJL/J mouse model of RR EAE. The results are the first to highlight the discrepancy between the clinical symptoms of EAE and TSPO expression in the brain, as measured by PET imaging at the peaks of various EAE episodes. The results suggest a significant role for PET imaging investigations of neuroinflammation in multiple sclerosis and allow for in vivo follow-up of antiinflammatory treatment strategies.

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Section: Discussionsupporting

confidence: 56%

Section: Discussionmentioning

confidence: 99%

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

et al. 2013

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“…Tracer uptake in the second episode was not significantly higher, but in the third episode, a significant increase was again observed. Uptake in all CNS regions decreased to control values in animals that recovered (regained weight, clinical score = 0) and did not enter a second episode, >10d after the first episode [53].…”

Section: Accepted Manuscriptmentioning

confidence: 88%

“…In order to quantify microglial activation during relapse-remitting EAE, [ [53]. Tracer uptake in the second episode was not significantly higher, but in the third episode, a significant increase was again observed.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Imaging of neuroinflammation in Alzheimer's disease, multiple sclerosis and stroke: Recent developments in positron emission tomography

Janssen

Vugts

Funke

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Neuroinflammation is thought to play a pivotal role in many diseases affecting the brain, including Alzheimer's disease, multiple sclerosis and stroke. Neuroinflammation is characterised predominantly by microglial activation, which can be visualised using positron emission tomography (PET). Traditionally, translocator protein 18kDa (TSPO) is the target for imaging of neuroinflammation using PET. In this review, recent preclinical and clinical research using PET in Alzheimer's disease, multiple sclerosis and stroke is summarised. In addition, new molecular targets for imaging of neuroinflammation, such as monoamine oxidases, adenosine receptors and cannabinoid receptor type 2, are discussed. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger.

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“…Most intriguing are the TSPO's relatively low concentrations in the CNS, particularly in microglia and astrocytes [ 3 , 4 ] that upon insult become activated resulting in significant overexpression in these cell types [ 5 – 7 ]. Consequently, TSPO overexpression has been confirmed in Alzheimer's disease (AD), multiple sclerosis, stroke, Parkinson's disease, HIV encephalitis, and trauma [ 7 – 11 ]. The observation that TSPO are also found in cancer cells [ 12 ] also suggests a role in cell proliferation, malignancy, and modulation of apoptosis [ 13 , 14 ].…”

Section: Introductionmentioning

confidence: 99%

Radiosynthesis,In VivoBiological Evaluation, and Imaging of Brain Lesions with [¹²³I]-CLINME, a New SPECT Tracer for the Translocator Protein

et al. 2015

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The high affinity translocator protein (TSPO) ligand 6-chloro-2-(4′-iodophenyl)-3-(N,N-methylethyl)imidazo[1,2-a]pyridine-3-acetamide (CLINME) was radiolabelled with iodine-123 and assessed for its sensitivity for the TSPO in rodents. Moreover neuroinflammatory changes on a unilateral excitotoxic lesion rat model were detected using SPECT imaging. [123I]-CLINME was prepared in 70–80% radiochemical yield. The uptake of [123I]-CLINME was evaluated in rats by biodistribution, competition, and metabolite studies. The unilateral excitotoxic lesion was performed by injection of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid unilaterally into the striatum. The striatum lesion was confirmed and correlated with TSPO expression in astrocytes and activated microglia by immunohistochemistry and autoradiography. In vivo studies with [123I]-CLINME indicated a biodistribution pattern consistent with TPSO distribution and the competition studies with PK11195 and Ro 5-4864 showed that [123I]-CLINME is selective for this site. The metabolite study showed that the extractable radioactivity was unchanged [123I]-CLINME in organs which expresses TSPO. SPECT/CT imaging on the unilateral excitotoxic lesion indicated that the mean ratio uptake in striatum (lesion : nonlesion) was 2.2. Moreover, TSPO changes observed by SPECT imaging were confirmed by immunofluorescence, immunochemistry, and autoradiography. These results indicated that [123I]-CLINME is a promising candidate for the quantification and visualization of TPSO expression in activated astroglia using SPECT.

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Assessment of Neuroinflammation in Transferred EAE Via a Translocator Protein Ligand

Cited by 3 publications

References 43 publications

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

Imaging of neuroinflammation in Alzheimer's disease, multiple sclerosis and stroke: Recent developments in positron emission tomography

Radiosynthesis,In VivoBiological Evaluation, and Imaging of Brain Lesions with [¹²³I]-CLINME, a New SPECT Tracer for the Translocator Protein

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Assessment of Neuroinflammation in Transferred EAE Via a Translocator Protein Ligand

Cited by 3 publications

References 43 publications

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

Central Nervous System Expression and PET Imaging of the Translocator Protein in Relapsing–Remitting Experimental Autoimmune Encephalomyelitis

Imaging of neuroinflammation in Alzheimer's disease, multiple sclerosis and stroke: Recent developments in positron emission tomography

Radiosynthesis,In VivoBiological Evaluation, and Imaging of Brain Lesions with [123I]-CLINME, a New SPECT Tracer for the Translocator Protein

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Product

Resources

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Radiosynthesis,In VivoBiological Evaluation, and Imaging of Brain Lesions with [¹²³I]-CLINME, a New SPECT Tracer for the Translocator Protein