TSPO imaging using the novel PET ligand [18F]GE-180: quantification approaches in patients with multiple sclerosis

Abstract

BackgroundPET ligands targeting the translocator protein (TSPO) represent promising tools to visualise neuroinflammation. Here, we analysed parameters obtained in dynamic and static PET images using the novel TSPO ligand [18F]GE-180 in patients with relapsing remitting multiple sclerosis (RRMS) and an approach for semi-quantitative assessment of this disease in clinical routine.Seventeen dynamic [18F]GE-180 PET scans of RRMS patients were evaluated (90 min). A pseudo-reference region (PRR) was defined after identification of the least disease-affected brain area by voxel-based comparison with six healthy controls (HC) and upon exclusion of voxels suspected of being affected in static 60–90 min p.i. images. Standardised uptake value ratios (SUVR) obtained from static images normalised to PRR were correlated to the distribution volume ratios (DVR) derived from dynamic data with Logan reference tissue model.ResultsGroup comparison with HC revealed white matter and thalamus as most affected regions. Fewest differences were found in grey matter, and normalisation to frontal cortex (FC) yielded the greatest reduction in variability of healthy grey and white matter. Hence, FC corrected for affected voxels was chosen as PRR, leading to time-activity curves of FC which were congruent to HC data (SUV60–90 0.37, U test P = 0.42). SUVR showed a very strong correlation with DVR (Pearson ρ > 0.9). Focal MS lesions exhibited a high SUVR (range, 1.3–3.2).ConclusionsThis comparison with parameters from dynamic data suggests that SUVR normalised to corrected frontal cortex as PRR is suitable for the quantification of [18F]GE-180 uptake in lesions and different brain regions of RRMS patients. This efficient diagnostic protocol based on static [18F]GE-180 PET scans acquired 60–90 min p.i. allows the semi-quantitative assessment of neuroinflammation in RRMS patients in clinical routine.

Confirmation of Specific Binding of the 18-kDa Translocator Protein (TSPO) Radioligand [18F]GE-180: a Blocking Study Using XBD173 in Multiple Sclerosis Normal Appearing White and Grey Matter

“…We also performed gadolinium contrast-enhancing MRI in the cohort of participants scanned with [ 18 F]GE-180 and observed no contrast enhancement (in lesion areas or otherwise), suggesting no extensive BBB breakdown. Although this observation does not exclude the possibility of micro-BBB breakdown, which could allow passage of [ 18 F]GE-180 molecules, but not the larger gadolinium molecules, through the disrupted area, the finding does concur with that of Vomacka et al [25]. The authors of this study also comment that (in their previous study [23]) areas with contrast enhancement in MR did not always correlate with increased [ 18 F]GE-180 signal, indicating that signal increases in PET are likely to be related to TSPO expression rather than exclusively BBB breakdown.…”

“…Participants had radial artery cannulation and blood was withdrawn continuously at a target rate of 2.5 ml min −1 from the start of each scan for the first 15 min. In addition, discrete blood samples were drawn at 0, 5, 10, 15, 30, 50, 70 and 90 min ([ 18 F]GE-180) or 0, 5,10,15,20,25,30,40,50,60,70,80 and 90 min ([ 11 C]PBR28) for metabolite analysis. For [ 18 F]GE-180, tracer concentrations in whole blood and plasma were measured in a well counter and radiometabolite analysis performed using two high performance liquid chromatography (HPLC) systems (Agilent 1260 Infinity and Agilent 110 Series) in isocratic mode.…”

Current Landscape and Emerging Fields of PET Imaging in Patients with Brain Tumors

“…The recently introduced TSPO ligand GE-180 labeled with [ 18 F] offers an increased binding specificity and was tested in patients with gliomas [113] and neuroinflammatory diseases such as multiple sclerosis [114][115][116]. Regarding the delineation of glioma extent, it has been demonstrated that the [ 18 F]GE-180 uptake volume is significantly larger than the volume of contrast enhancement [113,117].…”

The Molecular Effects of Ionizing Radiations on Brain Cells: Radiation Necrosis vs. Tumor Recurrence

“…One of the most interesting application is in patients with multiple sclerosis in which 18 F-GE180 already proved to be useful in the semi-quantitative assessment of neuroinflammation. In their work, Vomacka et al performed dynamic 18 F-GE180 PET scan (about 90 min) on 17 patients with relapsing remitting multiple sclerosis and subsequent static images in order to obtain SUV ratios that exhibited high values (ranging from 1.3 to 3.2) compared to frontal cortex, which was chosen as a pseudo-reference region as the least disease-affected brain area [75]. The duration of dynamic acquisition was based on the first human PET study on 18 F-GE180 that dates back to 2016, in which the authors evaluated after a 210-min acquisition on 10 healthy patients, five different kinetic models and concluded that the best represented brain 18 F-GE180 kinetics across regions was the reversible two-tissue compartment model (2TCM4k).…”