TSPO PET with [18F]GE-180 sensitively detects focal neuroinflammation in patients with relapsing-remitting multiple sclerosis

Purpose Expression of the translocator protein (TSPO) is upregulated in activated macrophages/microglia and is considered to be a marker of neuroinflammation. We investigated the novel TSPO ligand [F-18]GE-180 in patients with relapsing-remitting multiple sclerosis (RRMS) to determine the feasibility of [F-18]GE-180 PET imaging in RRMS patients and to assess its ability to detect active inflammatory lesions in comparison with the current gold standard, contrast-enhanced magnetic resonance imaging (MRI). Methods Nineteen RRMS patients were prospectively included in this study. All patients underwent TSPO genotyping and were classified as high-affinity, medium-affinity or low-affinity binders (HAB/MAB/LAB). PET scans were performed after administration of 189 +/- 12 MBq [F-18]GE-180, and 60-90 min summation images were used for visual analysis and assessment of standardized uptake values (SUV). The frontal nonaffected cortex served as a pseudoreference region (PRR) for evaluation of SUV ratios (SUVR). PET data were correlated with MRI signal abnormalities, i.e. T2 hyperintensity or contrast enhancement (CE). When available, previous MRI data were used to follow the temporal evolution of individual lesions. Resuts Focal lesions were identified as hot spots by visual inspection. Such lesions were detected in 17 of the 19 patients and overall 89 [F-18]GE-180-positive lesions were found. TSPO genotyping revealed 11 patients with HAB status, 5 with MAB status and 3 with LAB status. There were no associations between underlying binding status (HAB, MAB and LAB) and the signal intensity in either lesions (SUVR 1.87 +/- 0.43, 1.95 +/- 0.48 and 1.86 +/- 0.80, respectively; p = 0.280) or the PRR (SUV 0.36 +/- 0.03, 0.40 +/- 0.06 and 0.37 +/- 0.03, respectively; p = 0.990). Of the 89 [F-18]GE-180-positive lesions, 70 showed CE on MRI, while the remainder presented as T2 lesions without CE. SUVR were significantly higher in lesions with CE than in those without (2.00 +/- 0.53 vs. 1.60 +/- 0.15; p = 0.001). Notably, of 19 [F-18]GE-180-positive lesions without CE, 8 previously showed CE, indicating that [F-18]GE-180 imaging may be able to detect lesional activity that is sustained beyond the blood-brain barrier breakdown. Conclusion [F-18]GE-180 PET can detect areas of focal macrophage/microglia activation in patients with RRMS in lesions with and without CE on MRI. Therefore, [F-18]GE-180 PET imaging is a sensitive and quantitative approach to the detection of active MS lesions. It may provide information beyond contrast-enhanced MRI and is readily applicable to all patients. [F-18]GE-180 PET imaging is therefore a promising new tool for the assessment of focal inflammatory activity in MS.