Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: A PET study with the TSPO molecular imaging biomarker [ C]vinpocetine

Gulyás, Balázs; Tóth, Miklós; Schain, Martin; Airaksinen, Anu J.; Vas, Ádám; Kostulas, Konstantinos; Lindström, Per; Hillert, Jan; Halldin, Christer

doi:10.1016/j.jns.2012.06.026

Cited by 93 publications

(64 citation statements)

References 66 publications

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“…They observed that the binding potential for 11 C-vinpocetine was greater than that obtained for 11 C-PK11195 in all evaluated regions, but the differences did not reach significance. 11 C-vinpocetine binding potential was greater in the peri-infarcted zone than in the ischaemic core, but the difference did not prove to be significant [32,33]. …”

Section: Discussionmentioning

confidence: 99%

Could 18 F-DPA-714 PET imaging be interesting to use in the early post-stroke period?

et al. 2014

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BackgroundCerebral stroke is a severe and frequent condition that requires rapid and reliable diagnosis. If administered shortly after the first symptoms manifest themselves, IV thrombolysis has been shown to increase the functional prognosis by restoring brain reperfusion. However, a better understanding of the pathophysiology of stroke should help to identify potential new therapeutic targets. Stroke is known to induce an inflammatory brain reaction that involves overexpression of the 18-kDa translocator protein (TSPO) in glial cells and infiltrated leukocytes, which can be visualised by positron emission tomography (PET). We aimed to evaluate post-stroke neuroinflammation using the PET TSPO radioligand 18 F-DPA-714.MethodsNine patients underwent 18 F-DPA-714 PET and magnetic resonance imaging (MRI) between 8 and 18 days after the ictus. Co-registration of MRI and PET images was used to define three volumes of interest (VOIs): core infarction, contralateral region, and cerebellum ipsilateral to the stroke lesion. Time activity curves were obtained from each VOI, and ratios of mean and maximum activities between the VOIs were calculated.ResultsWe observed an increased uptake of 18 F-DPA-714 co-localised with the infarct tissue and extension beyond the region corresponding to the damage in the blood brain barrier. No correlation was identified between 18 F-DPA-714 uptake and infarct volume. 18 F-DPA-714 uptake in ischemic lesion (mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood) slowly decreased from 10 min pi to the end of the PET acquisition, remaining higher than that in both contralateral region and ipsilateral cerebellum.ConclusionOur results show that 18 F-DPA-714 uptake after acute ischemia is mainly associated with TSPO expression in the infarct area and in the surrounding neighbourhood. We also demonstrated that the kinetics of 18 F-DPA-714 differs in injured tissue compared to normal tissue. Therefore, 18 F-DPA-714 may be useful in assessing the extent of neuroinflammation associated with acute stroke and could also help to predict clinical outcomes and functional recovery, as well as to assess therapeutic strategies, such as the use of neuroprotective/anti-inflammatory drugs.

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Section: Discussionmentioning

confidence: 99%

Could 18 F-DPA-714 PET imaging be interesting to use in the early post-stroke period?

et al. 2014

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“…Although the TSPO was originally thought to be exclusively upregulated on microglia in disease states, recent studies have also demonstrated increased expression on astrocytes in humans, as well as in rodent models (Cosenza-Nashat et al, 2009; Lavisse et al, 2012), as shown in Figure 2. Consequently, interest has grown in the development and use of radiolabeled compounds against TSPO for imaging neuroinflammation in diverse CNS pathologies, such as multiple sclerosis (Harberts et al, 2012), dementia (Cagnin et al, 2001), Alzheimer's disease (Versijpt et al, 2003) and stroke (Gulyas et al, 2012a,b), as reviewed in (Ching et al, 2012). …”

Section: Imaging Astrocytes In Vivomentioning

confidence: 99%

The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

O’Brien¹,

Howarth²,

Sibson³

2013

Front. Cell. Neurosci.

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Brain metastasis is a significant clinical problem, yet the mechanisms governing tumor cell extravasation across the blood-brain barrier (BBB) and CNS colonization are unclear. Astrocytes are increasingly implicated in the pathogenesis of brain metastasis but in vitro work suggests both tumoricidal and tumor-promoting roles for astrocyte-derived molecules. Also, the involvement of astrogliosis in primary brain tumor progression is under much investigation. However, translation of in vitro findings into in vivo and clinical settings has not been realized. Increasingly sophisticated resources, such as transgenic models and imaging technologies aimed at astrocyte-specific markers, will enable better characterization of astrocyte function in CNS tumors. Techniques such as bioluminescence and in vivo fluorescent cell labeling have potential for understanding the real-time responses of astrocytes to tumor burden. Transgenic models targeting signaling pathways involved in the astrocytic response also hold great promise, allowing translation of in vitro mechanistic findings into pre-clinical models. The challenging nature of in vivo CNS work has slowed progress in this area. Nonetheless, there has been a surge of interest in generating pre-clinical models, yielding insights into cell extravasation across the BBB, as well as immune cell recruitment to the parenchyma. While the function of astrocytes in the tumor microenvironment is still unknown, the relationship between astrogliosis and tumor growth is evident. Here, we review the role of astrogliosis in both primary and secondary brain tumors and outline the potential for the use of novel imaging modalities in research and clinical settings. These imaging approaches have the potential to enhance our understanding of the local host response to tumor progression in the brain, as well as providing new, more sensitive diagnostic imaging methods.

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“…In an AD model, Maeda et al 53 found elevated TSPO levels in tau-rich hippocampus and entorhinal cortex region of the brain by 11 C-AC-5216 microPET, and there was a constant increase of tracer uptake in the brain region with the progression of AD. In a clinical study, Gulyás et al used 11 C-vinpocetine (ethyl apovincaminate) to evaluate the TSPO levels in the brains of stroke patients and found different uptake patterns in ischemic cores and peri-infarct zone over time 54.…”

Section: Biomarkers For Inflammation Imagingmentioning

confidence: 99%

PET Imaging of Inflammation Biomarkers

Wu¹,

Li²,

Niu³

et al. 2013

Theranostics

163

114

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Inflammation plays a significant role in many disease processes. Development in molecular imaging in recent years provides new insight into the diagnosis and treatment evaluation of various inflammatory diseases and diseases involving inflammatory process. Positron emission tomography using 18F-FDG has been successfully applied in clinical oncology and neurology and in the inflammation realm. In addition to glucose metabolism, a variety of targets for inflammation imaging are being discovered and utilized, some of which are considered superior to FDG for imaging inflammation. This review summarizes the potential inflammation imaging targets and corresponding PET tracers, and the applications of PET in major inflammatory diseases and tumor associated inflammation. Also, the current attempt in differentiating inflammation from tumor using PET is also discussed.

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Evolution of microglial activation in ischaemic core and peri-infarct regions after stroke: A PET study with the TSPO molecular imaging biomarker [ C]vinpocetine

Cited by 93 publications

References 66 publications

Could 18 F-DPA-714 PET imaging be interesting to use in the early post-stroke period?

Could 18 F-DPA-714 PET imaging be interesting to use in the early post-stroke period?

The role of astrocytes in CNS tumors: pre-clinical models and novel imaging approaches

PET Imaging of Inflammation Biomarkers

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