RT Journal Article SR Electronic T1 11C-DPA-713 versus 18F-GE-180: A preclinical comparison of TSPO-PET tracers to visualize acute and chronic neuroinflammation in a mouse model of ischemic stroke JF Journal of Nuclear Medicine JO J Nucl Med FD Society of Nuclear Medicine SP jnumed.118.209155 DO 10.2967/jnumed.118.209155 A1 Aisling Chaney A1 Haley C. Cropper A1 Emily M. Johnson A1 Kendra J. Lechtenberg A1 Todd C. Peterson A1 Marc Y. Stevens A1 Marion S. Buckwalter A1 Michelle L. James YR 2018 UL http://jnm.snmjournals.org/content/early/2018/07/05/jnumed.118.209155.abstract AB Neuroinflammation plays a key role in neuronal injury following ischemic stroke. Positron emission tomography (PET) imaging of translocator protein 18 kDa (TSPO) permits longitudinal, non-invasive visualization of neuroinflammation in both pre-clinical 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 two promising second-generation TSPO tracers; 11C-DPA-713 and 18F-GE-180, for the first time at acute and chronic time-points following ischemic stroke. Methods: Following distal middle cerebral artery occlusion (dMCAO) or sham surgery, mice underwent consecutive PET/CT imaging with 11C-DPA-713 and 18F-GE-180 at 2, 6, and 28 days after stroke. T2-weighted magnetic resonance (MR) images were acquired to enable delineation of ipsilateral (infarct) and contralateral brain regions of interest (ROIs). PET images were analyzed by calculating % injected dose per gram (%ID/g) in MR-guided ROIs. Standardized uptake value ratios were determined using the contralateral thalamus as a pseudo-reference region (SUVTh). Ex vivo autoradiography and immunohistochemistry were performed to verify in vivo findings. Results: Significantly increased tracer uptake was observed in the ipsilateral compared to 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 (CD68 immunostaining) and 11C-DPA-713-PET signal, that was not evident with 18F-GE-180. No significant correlations were observed between TSPO-PET and activated astrocytes (GFAP immunostaining). Conclusion: Both 11C-DPA-713 and 18F-GE-180-PET enable detection of neuroinflammation at early and chronic time-points following cerebral ischemia in mice. 11C-DPA-713-PET reflects the extent of microglial activation in infarcted dMCAO mouse brain tissue more accurately compared to 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 warrants further investigation in both pre-clinical and clinical settings.