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

Abstract

Background: Cerebral 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.

Methods: Nine 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.

Results: We 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.

Conclusion: Our 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.

Keywords: 18 F-DPA-714; Neuroinflammation; PET; Stroke.

Figure 1

Axial images obtained after vascular injury. The imaging studies were performed 13 days post-stroke. The infarct volume evaluated on MRI was 13 cm³. (A) Flair T2-weighted MR image. Left fronto-insular hypersignal demonstrating infarcted tissue. (B) Post-gadolinium T1-weighted MR image. Enhancement signal in the left fronto-insular cortex corresponding to the breakdown of BBB. (C) Co-registration image obtained between the post-gadolinium T1 MRI and PET. Note the absence of ¹⁸ F-DPA-714 uptake by the multiple bilateral nodular hypersignals within the white matter in connection with leukoaraïosis lesions.

Figure 2

TACs of ¹⁸   F-DPA-714 binding on the injured tissue (IT), contralateral (CL) normal tissue and ipsilateral cerebellum.

Figure 3

Ratio values calculated between injured tissue and two reference regions (contralateral (CL) and ipsilateral cerebellum).