Abstract
Neuroinflammation plays a key role in neuronal injury after ischemic stroke. PET imaging of translocator protein 18 kDa (TSPO) permits longitudinal, noninvasive visualization of neuroinflammation in both preclinical and clinical settings. Many TSPO tracers have been developed, however, it is unclear which tracer is the most sensitive and accurate for monitoring the in vivo spatiotemporal dynamics of neuroinflammation across applications. Hence, there is a need for head-to-head comparisons of promising TSPO PET tracers across different disease states. Accordingly, the aim of this study was to directly compare 2 promising second-generation TSPO tracers, 11C-DPA-713 and 18F-GE-180, for the first time at acute and chronic time points after ischemic stroke. Methods: After distal middle cerebral artery occlusion or sham surgery, mice underwent consecutive PET/CT imaging with 11C-DPA-713 and 18F-GE-180 at 2, 6, and 28 d after stroke. T2-weighted MR images were acquired to enable delineation of ipsilateral (infarct) and contralateral brain regions of interest (ROIs). PET/CT images were analyzed by calculating percentage injected dose per gram in MR-guided ROIs. SUV ratios were determined using the contralateral thalamus (SUVTh) as a pseudoreference region. Ex vivo autoradiography and immunohistochemistry were performed to verify in vivo findings. Results: Significantly increased tracer uptake was observed in the ipsilateral compared with contralateral ROI (SUVTh, 50–60 min summed data) at acute and chronic time points using 11C-DPA-713 and 18F-GE-180. Ex vivo autoradiography confirmed in vivo findings demonstrating increased TSPO tracer uptake in infarcted versus contralateral brain tissue. Importantly, a significant correlation was identified between microglial/macrophage activation (cluster of differentiation 68 immunostaining) and 11C-DPA-713- PET signal, which was not evident with 18F-GE-180. No significant correlations were observed between TSPO PET and activated astrocytes (glial fibrillary acidic protein immunostaining). Conclusion: 11C-DPA-713 and 18F-GE-180 PET enable detection of neuroinflammation at acute and chronic time points after cerebral ischemia in mice. 11C-DPA-713 PET reflects the extent of microglial activation in infarcted distal middle cerebral artery occlusion mouse brain tissue more accurately than 18F-GE-180 and appears to be slightly more sensitive. These results highlight the potential of 11C-DPA-713 for tracking microglial activation in vivo after stroke and warrant further investigation in both preclinical and clinical settings.
Highlights
More accurately than 18F-GE-180 and appears to be slightly more sensitive
translocator protein kDa (TSPO) expression is high in peripheral tissues, including kidneys, lungs, and steroid-associated tissues, and low in healthy brain tissue, where it is mainly restricted to microglia, and to a lesser extent astrocytes [8,9]
We investigated the utility of TSPO PET for quantifying alterations in peripheral inflammatory responses in the spleen
Summary
More accurately than 18F-GE-180 and appears to be slightly more sensitive. These results highlight the potential of 11C-DPA-713 for tracking microglial activation in vivo after stroke and warrant further investigation in both preclinical and clinical settings. The connection between neuroinflammation and ischemic stroke is unrefuted, the in vivo spatiotemporal dynamics of specific immune cells, at acute and chronic time points, in individual stroke patients is poorly understood. How these immune signatures relate to clinical outcomes remains unknown. Investigating the multifaceted molecular aspects of the innate and adaptive immune response in the central nervous system after stroke is mostly restricted to in vitro postmortem analyses (e.g., immunologic assays) These techniques continue to provide invaluable insights into the complex neuroimmune interactions after ischemia, they are limited to a single time point of inquiry and cannot provide in vivo longitudinal data needed to elucidate this dynamic process. Animals were administered subcutaneous cefazolin, 25 mg/kg (VWR #89149-888) and buprenorphine SR, 1 mg/kg (Zoopharm) and were monitored until fully ambulatory
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
