Abstracts

Rationale: Neuroinflammation may play a role in epilepsy. Translocator protein 18kDa (TSPO), a biomarker for neuroinflammation, is overexpressed on activated microglia and reactive astrocytes. TSPO can be imaged quantifiably in vivo using the PET ligand [¹¹C]PBR28. We previously showed that [¹¹C]PBR28 uptake is higher ipsilateral than contralateral to seizure foci in patients with temporal lobe epilepsy (TLE).¹ [¹¹C]DPA-713, another second-generation TSPO radioligand, may have superior imaging characteristics. To date, [¹¹C]DPA-713 has only been studied in healthy subjects. Here, we sought (1) to replicate findings of greater TSPO ipsilateral than contralateral to seizure foci in a larger TLE sample, (2) to determine whether similar results could be obtained with [¹¹C]DPA-713, and (3) to compare [¹¹C]PBR28 and [¹¹C]DPA-713 sensitivities for detecting inflammation in epileptic focus. 1. Hirvonen et al. J Nucl Med. 2012;53(2):234-240. Methods: We scanned 23 TLE patients with [¹¹C]PBR28; eight also had [¹¹C]DPA-713 scans. Six brain regions were delineated using freesurfer and T1-weighted MRI: hippocampus, amygdala, temporal cortex, temporal pole, fusiform gyrus, and entorhinal cortex/parahippocampal gyrus. We compared brain uptake of each radioligand in ipsilateral and contralateral regions, and calculated absolute asymmetry indices [AIs, 200% *(ipsilateral-contralateral)/(ipsilateral+contralateral] to compare the ligands. Results: TLE patients had higher uptake of both [¹¹C]PBR28 (range, 2% to 6%), and [¹¹C]DPA-713 (4 to 9%) in ipsilateral regions (fig 1). Mean differences for both ligands reached statistical significance in most regions. AIs of [¹¹C]DPA-713 were significantly higher than those of [¹¹C]PBR28 in temporal pole (9% vs 4%, p = 0.02) and entorhinal cortex/parahippocampal gyrus (6% vs 3%. p = 0.04; figure 2). Conclusions: We found increased TSPO in ipsilateral relative to contralateral regions, measured by two radioligands - [¹¹C]PBR28 and [¹¹C]DPA-713. In addition, [¹¹C]DPA-713 may have a higher ratio of specific to non-displaceable binding and therefore greater sensitivity to localize inflammation in TLE. In vivo displacement studies are needed to determine the specific and non-displaceable binding of these radioligands. Our study shows that PET can detect neuroinflammation in TLE, and suggests a potential role for new therapeutic approaches.