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

Abstract

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.

Immune interventions in stroke

“…For example, activated microglia can be visualized in humans by using a PET ligand that binds to microglia translocator protein or by using a PET tracer ( l -deuteriodeprenyl) to reveal reactive astrocytes during brain inflammation. 111,112 Ultrasmall superparamagnetic iron oxide contrast agent-enhanced MRI can be used to study the role of macrophages in the development of ischaemic lesions in experimental ischaemia and human stroke. 113–115 This approach can shed light on the roles of these cells after onset of ischaemia, and could determine when immune status is altered after disease onset by revealing morphological features of the cells.…”

A Facile Radiolabeling of [18F]FDPA via Spirocyclic Iodonium Ylides: Preliminary PET Imaging Studies in Preclinical Models of Neuroinflammation

“…14, 15 Initial evaluation of this radiopharmaceutical in healthy human volunteers validated its biodistribution profile towards TSPO. 16 Clinical PET studies using [ 18 F]1 were further conducted on patients with amyotrophic lateral sclerosis, 17 post-stroke 18 and AD, 19 demonstrating this ligand may be useful in assessing the extent of neuroinflammation.…”

Optimized Quantification of Translocator Protein Radioligand 18F-DPA-714 Uptake in the Brain of Genotyped Healthy Volunteers

“…Recent preclinical studies (7-9) have identified 18 F-DPA-714 as a promising TSPO ligand for in vivo imaging, and 18 F-DPA-714 has been used to quantify TSPOs in healthy subjects (10) and in amyotrophic lateral sclerosis, Alzheimer, or stroke patients (11)(12)(13). In most studies, quantification was performed without arterial samples or metabolite analysis and was based either on a simplified compartmental model (the cerebellum as a reference region (10,12)) or on a cluster analysis (10,11,13).…”

“…In most studies, quantification was performed without arterial samples or metabolite analysis and was based either on a simplified compartmental model (the cerebellum as a reference region (10,12)) or on a cluster analysis (10,11,13).…”