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European Journal of Nuclear Medicine and Molecular Imaging

Published in:

01-07-2014 | Original Article

PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714

Authors: Yu Wang, Xuyi Yue, Dale O. Kiesewetter, Gang Niu, Gaojun Teng, Xiaoyuan Chen

Published in: European Journal of Nuclear Medicine and Molecular Imaging | Issue 7/2014

Abstract

Purpose

The inflammatory response in injured brain parenchyma after traumatic brain injury (TBI) is crucial in the pathological process. In order to follow microglia activation and neuroinflammation after TBI, we performed PET imaging in a rat model of TBI using ¹⁸F-labeled DPA-714, a ligand of the 18-kDa translocator protein (TSPO).

Methods

TBI was induced in male SD rats by a controlled cortical impact. The success of the TBI model was confirmed by MRI. [¹⁸F]DPA-714 was synthesized using a slightly modified TRACERLab FX-FN module and an automated procedure. In vivo PET imaging was performed at different time points after surgery using an Inveon small-animal PET scanner. The specificity of [¹⁸F]DPA-714 was confirmed by a displacement study with an unlabeled competitive TSPO ligand, PK11195. Ex vivo autoradiography as well as immunofluorescence staining was carried out to confirm the in vivo PET results.

Results

Both in vivo T₂-weighted MR images and ex vivo TTC staining results revealed successful establishment of the TBI model. Compared with the sham-treated group, [¹⁸F]DPA-714 uptake was significantly higher in the injured brain area on PET images. Increased lesion-to-normal ratios of [¹⁸F]DPA-714 were observed in the brain of TBI rats on day 2 after surgery. Ratios peaked around day 6 (2.65 ± 0.36) and then decreased gradually to nearly normal levels on day 28. The displacement study using PK11195 confirmed the specific binding of [¹⁸F]DPA-714 to TSPO. The results of ex vivo autoradiography were consistent with in vivo PET results. Immunofluorescence staining showed the time course of TSPO expression after TBI and the temporal and the spatial distribution of microglia in the damaged brain area.

Conclusion

TSPO-targeted PET using [¹⁸F]DPA-714 as the imaging probe can be used to dynamically monitor the inflammatory response after TBI in a noninvasive manner. This method will not only facilitate a better understanding of the inflammatory process after TBI, but also provide a useful in vivo monitoring strategy for antiinflammation therapy of TBI.

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Title: PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714
Authors: Yu Wang
Xuyi Yue
Dale O. Kiesewetter
Gang Niu
Gaojun Teng
Xiaoyuan Chen
Publication date: 01-07-2014
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nuclear Medicine and Molecular Imaging / Issue 7/2014
Print ISSN: 1619-7070
Electronic ISSN: 1619-7089
DOI: https://doi.org/10.1007/s00259-014-2727-5

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

PET imaging of neuroinflammation in a rat traumatic brain injury model with radiolabeled TSPO ligand DPA-714

Abstract

Purpose

Methods

Results

Conclusion

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

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