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Published June 6, 2014 | Version v1
Journal article Open

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

  • 1. Université François Rabelais de Tours, UMR-S930 Tours, France; Inserm U930, University of Tours, Tours 37000, France; CHRU Tours, Tours 37000, France; CIC-IT INSERM 806 Ultrasons et Radiopharmaceutiques, Tours, France and Service de Médecine Nucléaire, Hôpital Bretonneau, 2, Boulevard Tonnellé, Tours CEDEX 37044, France.
  • 2. Université François Rabelais de Tours, UMR-S930 Tours, France and Inserm U930, University of Tours, Tours 37000, France.
  • 3. CHRU Tours, Tours 37000, France.
  • 4. Université François Rabelais de Tours, UMR-S930 Tours, France; Inserm U930, University of Tours, Tours 37000, France and CHRU Tours, Tours 37000, France.
  • 5. Université François Rabelais de Tours, UMR-S930 Tours, France; Inserm U930, University of Tours, Tours 37000, France; CHRU Tours, Tours 37000, France and CIC INSERM 202, Tours, France.
  • 6. School of Chemistry, University of Sydney, Sydney, New South Wales 2006, Australia and Brain and Mind Research Institute, Sydney, New South Wales 2050, Australia.
  • 7. School of Chemistry, University of Sydney, Sydney, New South Wales 2006, Australia; Brain and Mind Research Institute, Sydney, New South Wales 2050, Australia and Discipline of Medical Radiation Sciences, University of Sydney, Sydney, New South Wales 2006, Australia.
  • 8. Université François Rabelais de Tours, UMR-S930 Tours, France; Inserm U930, University of Tours, Tours 37000, France; CHRU Tours, Tours 37000, France; CIC-IT INSERM 806 Ultrasons et Radiopharmaceutiques, Tours, France and CIC INSERM 202, Tours, France.

Description

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.

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Additional details

Funding

INMIND – Imaging of Neuroinflammation in Neurodegenerative Diseases 278850
European Commission