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.

Highlights

  • positron emission tomography (PET) ligands targeting the translocator protein (TSPO) represent promising tools to visualise neuroinflammation

  • This study aimed to provide a robust, clinically suitable quantification approach for the third-generation TSPO ligand [18F]GE-180 in multiple sclerosis (MS) patients

  • Binding potentials derived with reference modelling (BP = distribution volume ratios (DVR) − 1) reported previously for the prototypic TSPO ligand [11C](R)-PK11195 in healthy controls, and MS patients were in a similar range as results presented here for [18F]GE-180: the lowest BP was found in normal-appearing white matter and the highest BP in the thalamus and the brainstem [23,24,25]

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Summary

Introduction

PET ligands targeting the translocator protein (TSPO) represent promising tools to visualise neuroinflammation. 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. The classic diagnosis of multiple sclerosis (MS) is based on clinical and paraclinical documentation of the dissemination of CNS lesions in time and space Such lesions and their evolution over time are commonly detected by magnetic resonance imaging (MRI). Quantification with [11C](R)-PK11195 has been shown to be challenging due to a low free fraction in plasma, a significant binding to plasma proteins, and a low extraction fraction in brain with a limited signal-to-background ratio [4, 5] This led to the development of second-generation TSPO radioligands with lower non-specific binding and higher affinity and specificity

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