Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution.

Autor:	Bartos LM; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Kirchleitner SV; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Kolabas ZI; Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center, Neuherberg, Munich, Germany.; Institute for Stroke and Dementia Research (ISD), University Hospital of Munich, LMU Munich, Munich, Germany.; Graduate School of Systemic Neurosciences (GSN), Munich, Germany., Quach S; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Beck A; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany., Lorenz J; Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany., Blobner J; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany., Mueller SA; Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany., Ulukaya S; Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center, Neuherberg, Munich, Germany.; Faculty of Biology, Master of Science Program in Molecular and Cellular Biology, Ludwig-Maximilians-Universität München, Planegg, Germany., Hoeher L; Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center, Neuherberg, Munich, Germany., Horvath I; Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center, Neuherberg, Munich, Germany.; School of Computation, Information and Technology (CIT), TUM, Boltzmannstr. 3, 85748 Garching, Germany., Wind-Mark K; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Holzgreve A; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Ruf VC; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany., Gold L; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Kunze LH; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Kunte ST; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Beumers P; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Park HE; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Antons M; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Zatcepin A; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany., Briel N; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany.; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany., Hoermann L; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Schaefer R; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Messerer D; Department of Cardiology, University Hospital of Munich, LMU Munich, Munich, Germany., Bartenstein P; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Riemenschneider MJ; Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany., Lindner S; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Ziegler S; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany., Herms J; Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany.; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Lichtenthaler SF; Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Ertürk A; Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center, Neuherberg, Munich, Germany.; Institute for Stroke and Dementia Research (ISD), University Hospital of Munich, LMU Munich, Munich, Germany.; Graduate School of Systemic Neurosciences (GSN), Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany., Tonn JC; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany., von Baumgarten L; Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany., Albert NL; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Bavarian Cancer Research Center (BZKF), Erlangen, Germany., Brendel M; Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.; DZNE-German Center for Neurodegenerative Diseases, Munich, Germany.; Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.
Jazyk:	angličtina
Zdroj:	Science advances [Sci Adv] 2023 Oct 27; Vol. 9 (43), pp. eadi8986. Date of Electronic Publication: 2023 Oct 27.
DOI:	10.1126/sciadv.adi8986
Abstrakt:	Various cellular sources hamper interpretation of positron emission tomography (PET) biomarkers in the tumor microenvironment (TME). We developed an approach of immunomagnetic cell sorting after in vivo radiotracer injection (scRadiotracing) with three-dimensional (3D) histology to dissect the cellular allocation of PET signals in the TME. In mice with implanted glioblastoma, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs), validated by protein levels. Translation of in vitro scRadiotracing to patients with glioma immediately after tumor resection confirmed higher single-cell TSPO tracer uptake of tumor cells compared to immune cells. Across species, cellular radiotracer uptake explained the heterogeneity of individual TSPO-PET signals. In consideration of cellular tracer uptake and cell type abundance, tumor cells were the main contributor to TSPO enrichment in glioblastoma; however, proteomics identified potential PET targets highly specific for TAMs. Combining cellular tracer uptake measures with 3D histology facilitates precise allocation of PET signals and serves to validate emerging novel TAM-specific radioligands.
Databáze:	MEDLINE
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