Mahler, Christoph and Schumacher, Adrian-Minh and Unterrainer, Marcus and Kaiser, Lena and Hollbacher, Thomas and Lindner, Simon and Havla, Joachim and Ertl-Wagner, Birgit and Patzig, Maximilian and Seelos, Klaus and Neitzel, Julia and Maurer, Matthias and Krumbholz, Markus and Metz, Imke and Bruck, Wolfgang and Stadelmann, Christine and Merkler, Doron and Gass, Achim and Milenkovic, Vladimir and Bartenstein, Peter and Albert, Nathalie L. and Kuempfel, Tania and Kerschensteiner, Martin (2021) TSPO PET imaging of natalizumab-associated progressive multifocal leukoencephalopathy. BRAIN, 144. pp. 2683-2695. ISSN 0006-8950, 1460-2156
Full text not available from this repository. (Request a copy)Abstract
Progressive multifocal leukoencephalopathy (PML) is a severe infection of the CNS caused by the polyomavirus JC that can occur in multiple sclerosis patients treated with natalizumab. Clinical management of patients with natalizumab-associated PML is challenging not least because current imaging tools for the early detection, longitudinal monitoring and differential diagnosis of PML lesions are limited. Here we evaluate whether translocator protein (TSPO) PET imaging can be applied to monitor the inflammatory activity of PML lesions over time and differentiate them from multiple sclerosis lesions. For this monocentre pilot study we followed eight patients with natalizumab-associated PML with PET imaging using the TSPO radioligand F-18-GE-180 combined with frequent 3T MRI. In addition we compared TSPO PET signals in PML lesions with the signal pattern of multiple sclerosis lesions from 17 independent multiple sclerosis patients. We evaluated the standardized uptake value ratio as well as the morphometry of the TSPO uptake for putative PML and multiple sclerosis lesions areas compared to a radiologically unaffected pseudo-reference region in the cerebrum. Furthermore, TSPO expression in situ was immunohistochemically verified by determining the density and cellular identity of TSPO-expressing cells in brain sections from four patients with early natalizumab-associated PML as well as five patients with other forms of PML and six patients with inflammatory demyelinating CNS lesions (clinically isolated syndrome/multiple sclerosis). Histological analysis revealed a reticular accumulation of TSPO expressing phagocytes in PML lesions, while such phagocytes showed a more homogeneous distribution in putative multiple sclerosis lesions. TSPO PET imaging showed an enhanced tracer uptake in natalizumab-associated PML lesions that was present from the early to the chronic stages (up to 52months after PML diagnosis). While gadolinium enhancement on MRI rapidly declined to baseline levels, TSPO tracer uptake followed a slow one phase decay curve. A TSPO-based 3D diagnostic matrix taking into account the uptake levels as well as the shape and texture of the TSPO signal differentiated >96% of PML and multiple sclerosis lesions. Indeed, treatment with rituximab after natalizumab-associated PML in three patients did not affect tracer uptake in the assigned PML lesions but reverted tracer uptake to baseline in the assigned active multiple sclerosis lesions. Taken together our study suggests that TSPO PET imaging can reveal CNS inflammation in natalizumab-associated PML. TSPO PET may facilitate longitudinal monitoring of disease activity and help to distinguish recurrent multiple sclerosis activity from PML progression.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TRANSLOCATOR PROTEIN; MULTIPLE-SCLEROSIS; MICROGLIAL ACTIVATION; ASYMPTOMATIC PML; BRAIN; NEUROINFLAMMATION; RADIOTRACER; MS; PATTERN; LESIONS; progressive multifocal leukoencephalopathy; multiple sclerosis; positron emission tomography; translocator protein; microglia |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 27 Sep 2022 06:13 |
| Last Modified: | 27 Sep 2022 06:13 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47992 |
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