TY - JOUR
T1 - 11 C-DPA-713 versus 18 F-GE-180
T2 - A preclinical comparison of translocator protein 18 kDa PET tracers to visualize acute and chronic neuroinflammation in a mouse model of ischemic stroke
AU - Chaney, Aisling
AU - Cropper, Haley C.
AU - Johnson, Emily M.
AU - Lechtenberg, Kendra J.
AU - Peterson, Todd C.
AU - Stevens, Marc Y.
AU - Buckwalter, Marion S.
AU - James, Michelle L.
N1 - Funding Information:
We are grateful for the support from the SCi3 small-animal imaging facility at Stanford. We also thank InviCRO for their assistance with VivoQuant software, and the Radiochemistry Facility, especially Dr. Jun Park.
Funding Information:
This project was funded partly by a ‘‘Big Ideas in Neuroscience’’ grant from the Stanford Neurosciences Institute to the Stroke Collaborative Action Network (Buckwalter). No other potential conflict of interest relevant to this article was reported.
Publisher Copyright:
Copyright © 2019 by the Society of Nuclear Medicine and Molecular Imaging.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - 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, 11 C-DPA-713 and 18 F-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 11 C-DPA-713 and 18 F-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 (SUV Th ) 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 (SUV Th , 50-60 min summed data) at acute and chronic time points using 11 C-DPA-713 and 18 F-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 11 C-DPA-713- PET signal, which was not evident with 18 F-GE-180. No significant correlations were observed between TSPO PET and activated astrocytes (glial fibrillary acidic protein immunostaining). Conclusion: 11 C-DPA-713 and 18 F-GE-180 PET enable detection of neuroinflammation at acute and chronic time points after cerebral ischemia in mice. 11 C-DPA-713 PET reflects the extent of microglial activation in infarcted distal middle cerebral artery occlusion mouse brain tissue more accurately than 18 F-GE-180 and appears to be slightly more sensitive. These results highlight the potential of 11 C-DPA-713 for tracking microglial activation in vivo after stroke and warrant further investigation in both preclinical and clinical settings.
AB - 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, 11 C-DPA-713 and 18 F-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 11 C-DPA-713 and 18 F-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 (SUV Th ) 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 (SUV Th , 50-60 min summed data) at acute and chronic time points using 11 C-DPA-713 and 18 F-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 11 C-DPA-713- PET signal, which was not evident with 18 F-GE-180. No significant correlations were observed between TSPO PET and activated astrocytes (glial fibrillary acidic protein immunostaining). Conclusion: 11 C-DPA-713 and 18 F-GE-180 PET enable detection of neuroinflammation at acute and chronic time points after cerebral ischemia in mice. 11 C-DPA-713 PET reflects the extent of microglial activation in infarcted distal middle cerebral artery occlusion mouse brain tissue more accurately than 18 F-GE-180 and appears to be slightly more sensitive. These results highlight the potential of 11 C-DPA-713 for tracking microglial activation in vivo after stroke and warrant further investigation in both preclinical and clinical settings.
KW - Ischemic stroke
KW - Neuroinflammation
KW - PET
KW - TSPO
UR - http://www.scopus.com/inward/record.url?scp=85059501692&partnerID=8YFLogxK
U2 - 10.2967/jnumed.118.209155
DO - 10.2967/jnumed.118.209155
M3 - Article
C2 - 29976695
AN - SCOPUS:85059501692
SN - 0161-5505
VL - 60
SP - 122
EP - 128
JO - Journal of Nuclear Medicine
JF - Journal of Nuclear Medicine
IS - 1
ER -