Allocation of TSPO-PET signals to cellular and extracellular compartments in dependence of blood-brain barrier disruption in experimental glioblastoma
11 affiliations
- 1Department of Nuclear Medicine, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany
- 2Institute for Stroke and Dementia Research, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany
- 3Department of Neurosurgery, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany
- 4Munich Cluster for Systems Neurology (SyNergy), Munich, Germany
- 5German Center for Neurodegenerative Diseases (DZNE) Munich, Munich, Germany
- 6Russell H. Morgan Department of Radiology and Radiological Sciences, Johns Hopkins School of Medicine, Baltimore, MD USA
- 7Department of Neurology, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany
- 8German Cancer Consortium (DKTK), Partner Site Munich, A Partnership Between the DKFZ Heidelberg and the University Hospital of the LMU, Munich, Germany
- 9Bavarian Cancer Research Center (BZKF), Partner Site Munich, Munich, Germany
- 10Institute of Clinical Neuroimmunology, LMU University Hospital, LMU Medizin, Ludwig-Maximilians-Universität München, Munich, Germany
- 11Biomedical Center (BMC), LMU Medizin, Ludwig-Maximilians-Universität München, Martinsried, Germany
Abstract
Background: Translocator protein (TSPO)-PET imaging facilitates monitoring of glioblastoma in preclinical models and patients. However, specificity of TSPO-PET signals remains to be investigated. In this study, we aimed to decipher exact contributions of cellular and extracellular compartments including the impact of blood-brain barrier (BBB) disruption to TSPO-PET signals in an experimental glioblastoma mouse model.
Methods: Mice with implanted glioblastoma (SB28; n = 36 early-stage, n = 39 late-stage; GFP(+)) were injected with the TSPO tracer [18F]GE-180 (21 MBq ± 1.5 MBq). Dynamic 60 min microPET scans were performed with and without prior blocking by excessive cold radiotracer. Tumors were dissociated, followed by cell sorting of tumor cells, tumor-associated microglia/macrophages (TAMs, CD11b(+)) and non-tumor/non-TAM (i.e. remaining) cells with subsequent gamma emission measures and flow cytometry (scRadiotracing) to calculate radioactivity per single cell. PET signals and single-cell tracer uptake in tumors and non-lesional hemispheres were compared between blocked and unblocked conditions. N = 10 mice were intravenously injected with fluorescent Dextran to investigate BBB disruption by confocal microscopy in correlation with TSPO-PET signals of the same animals.
Results: TSPO-PET indicated strong but incomplete signal reduction after blocking in tumors (early-stage: -72%; late-stage: -59%, p < 0.001) and contralateral hemispheres (early stage: -65%, late-stage: -63%, p < 0.001) compared to unblocked animals. We found nearly complete blocking of radiotracer uptake across all analyzed cell fractions (tumor cells: -95%, p = 0.0039; TAMs: -98%, p < 0.0001; remaining cells: -99%, p = 0.0033) compared to unblocked mice, regardless of tumor stages. There was a significant correlation of PET signal reduction (R=-0.824, p = 0.0034) as well as residual PET signal upon blocking (R = 0.809, p = 0.0046) with Dextran intensity.
Conclusion: Specificity of TSPO-PET signals in experimental glioblastoma reaches 72% in early-stage tumors, but decreases to 59% in late-stage SB28 tumors, due to progressive contributions of BBB disruption. Non-specific TSPO tracer uptake is driven by BBB disruption and fully allocated to the extracellular compartment, whereas cellular TSPO tracer uptake shows strong specificity.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08187-5.
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BibTeX
@article{hoermann2026allocation,
title = {{Allocation of TSPO-PET signals to cellular and extracellular compartments in dependence of blood-brain barrier disruption in experimental glioblastoma}},
author = {Leonie Hoermann and Fatma Burcu Seker and Emanuel Joseph and Sabrina V Kirchleitner and Jens Blobner and Lea H Kunze and Justus F Thevis and Selina Hummel and Amelie L Englert and Karin Wind-Mark and Adrien Holzgreve and Simon Lindner and Rudolf A Werner and Louisa von Baumgarten and Nathalie L Albert and Nikolaus Plesnila and Matthias Brendel and Laura M Bartos},
journal = {European Journal of Nuclear Medicine and Molecular Imaging},
year = {2026},
month = sep,
doi = {10.1007/s00259-026-08187-5},
url = {https://doi.org/10.1007/s00259-026-08187-5},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Allocation of TSPO-PET signals to cellular and extracellular compartments in dependence of blood-brain barrier disruption in experimental glioblastoma
AU - Leonie Hoermann
AU - Fatma Burcu Seker
AU - Emanuel Joseph
AU - Sabrina V Kirchleitner
AU - Jens Blobner
AU - Lea H Kunze
AU - Justus F Thevis
AU - Selina Hummel
AU - Amelie L Englert
AU - Karin Wind-Mark
AU - Adrien Holzgreve
AU - Simon Lindner
AU - Rudolf A Werner
AU - Louisa von Baumgarten
AU - Nathalie L Albert
AU - Nikolaus Plesnila
AU - Matthias Brendel
AU - Laura M Bartos
PY - 2026
DA - 2026/09/24
JO - European Journal of Nuclear Medicine and Molecular Imaging
DO - 10.1007/s00259-026-08187-5
UR - https://doi.org/10.1007/s00259-026-08187-5
AB - Background: Translocator protein (TSPO)-PET imaging facilitates monitoring of glioblastoma in preclinical models and patients. However, specificity of TSPO-PET signals remains to be investigated. In this study, we aimed to decipher exact contributions of cellular and extracellular compartments including the impact of blood-brain barrier (BBB) disruption to TSPO-PET signals in an experimental glioblastoma mouse model. Methods: Mice with implanted glioblastoma (SB28; n = 36 early-stage, n = 39 late-stage; GFP(+)) were injected with the TSPO tracer [18F]GE-180 (21 MBq ± 1.5 MBq). Dynamic 60 min microPET scans were performed with and without prior blocking by excessive cold radiotracer. Tumors were dissociated, followed by cell sorting of tumor cells, tumor-associated microglia/macrophages (TAMs, CD11b(+)) and non-tumor/non-TAM (i.e. remaining) cells with subsequent gamma emission measures and flow cytometry (scRadiotracing) to calculate radioactivity per single cell. PET signals and single-cell tracer uptake in tumors and non-lesional hemispheres were compared between blocked and unblocked conditions. N = 10 mice were intravenously injected with fluorescent Dextran to investigate BBB disruption by confocal microscopy in correlation with TSPO-PET signals of the same animals. Results: TSPO-PET indicated strong but incomplete signal reduction after blocking in tumors (early-stage: -72%; late-stage: -59%, p < 0.001) and contralateral hemispheres (early stage: -65%, late-stage: -63%, p < 0.001) compared to unblocked animals. We found nearly complete blocking of radiotracer uptake across all analyzed cell fractions (tumor cells: -95%, p = 0.0039; TAMs: -98%, p < 0.0001; remaining cells: -99%, p = 0.0033) compared to unblocked mice, regardless of tumor stages. There was a significant correlation of PET signal reduction (R=-0.824, p = 0.0034) as well as residual PET signal upon blocking (R = 0.809, p = 0.0046) with Dextran intensity. Conclusion: Specificity of TSPO-PET signals in experimental glioblastoma reaches 72% in early-stage tumors, but decreases to 59% in late-stage SB28 tumors, due to progressive contributions of BBB disruption. Non-specific TSPO tracer uptake is driven by BBB disruption and fully allocated to the extracellular compartment, whereas cellular TSPO tracer uptake shows strong specificity. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00259-026-08187-5.
SN - 1619-7070
SN - 1619-7089
ER -