PET in vivo imaging of 18kDa TSPO expression in a mouse model of temporal lobe epilepsy using [18F]DPA-714

Objectives Mesial temporal lobe epilepsy (MTLE) is the most common type of epilepsy. Neuroinflammation plays a role in the pathophysiology of the disease. We studied whether 18kDa TSPO was a good neuroinflammatory marker using [18F]DPA-714 PET to monitor the disease processes in a mouse model of MTLE.

Methods The model was induced by unilateral injection of kainic acid (KA) (0,2µg/50nl) into the right dorsal hippocampus of male C57/Bl6 mice. Sham mice were also prepared by injecting 50nl of physiological saline at the same location. PET/CT scanning (60 min duration, Inveon Scanner, Siemens) was performed in 4 independent mice populations: 7 days (KA_7_days population, n=5) and 1 month (KA_1_month population, n=8) after KA injection, 7 days (Sham_7_days population, n=5) and 1 month (Sham_1_month population, n=5) after saline injection. 11 naive mice were also scanned and served as a baseline population to compare with KA and sham populations. About 7.4 MBq [18F]DPA-714 (0.05-1.92 nmol of injected mass) was infused for 1 minute in the lateral tail vein for dynamic PET/CT imaging. Brain PET/CT images were reconstructed using OSEM 2D algorithm with attenuation correction during reconstruction. These images were then coregistered to a MRI template atlas in PMOD 3.6. Right, left hippocampus and cerebellum regions of interest were determined based on the standard regions of interest extracted from this MRI template atlas. The uptake in right and left hippocampus were summed over 60 min and normalized to the cerebellum uptake.

Results An intense and diffuse uptake was observed in both hippocampi 7 days after KA injection, predominant at the side of injection compared to the naive mice (right: 1.06±0.04 vs 0.81±0.04, p<0.0001 and left: 0.96±0.03 vs 0.77±0.05, p<0.0001). A high and diffuse uptake was also observed in both hippocampi in sham mice at 7 days compared to the naive mice (right: 0.88±0.03, p=0.004 and left: 0.83±0.02, p=0.02). Compared to the intense uptake in KA 7 days mice, the sham 7 days diffuse uptakes resulted from the systemic inflammatory reaction after surgery (ventricle system, surgery site). One month after injection, the uptake in right hippocampus in KA mice decreased and was more localized but remained significantly higher than that in the baseline right hippocampus (0.90±0.06, p=0.0011) while the uptake in left hippocampus returned to the baseline signal (0.81±0.03, NS). No increase of uptake was observed in both hippocampi of sham mice at 1 month compared to the baseline mice (right: 0.79±0.03, NS and left: 0.74±0.05, NS).

Conclusions [18F]DPA-714 is a promising radiotracer for imaging the inflammatory process in MTLE during epileptogenesis and ictogenesis, although the interpretation of high uptake signal at early imaging PET is impaired by the local inflammation induced by the needle insertion (sham mice). Tracer quantification in the hippocampus is also largely affected by partial volume effect due to the small size of this structure. Further image processing and more sophisticated quantification should help reduce the partial volume effect and improve quantitative accuracy so that the pattern of TSPO expression in longitudinal studies can be precisely characterized. $$graphic_15C50B5D-0201-4A45-9EE7-1B358E14A395$$ $$graphic_6E333DFB-AE84-4A31-88E2-A780609FD125$$

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