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Bartos, L.M.* ; Kirchleitner, S.V.* ; Kolabas, Z.I. ; Quach, S.* ; Beck, A.* ; Lorenz, J.* ; Blobner, J.* ; Mueller, S.A.* ; Ulukaya, S. ; Höher, L. ; Horvath, I. ; Wind-Mark, K.* ; Holzgreve, A.* ; Ruf, V.C.* ; Gold, L.* ; Kunze, L.H.* ; Kunte, S.T.* ; Beumers, P.* ; Park, H.E.* ; Antons, M.* ; Zatcepin, A.* ; Briel, N.* ; Hoermann, L.* ; Schaefer, R.* ; Messerer, D.* ; Bartenstein, P.* ; Riemenschneider, M.J.* ; Lindner, S.* ; Ziegler, S.* ; Herms, J.* ; Lichtenthaler, S.F.* ; Ertürk, A. ; Tonn, J.C.* ; von Baumgarten, L.* ; Albert, N.L.* ; Brendel, M.*

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

Sci. Adv. 9:eadi8986 (2023)
Publ. Version/Full Text DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Tspo; Platform; Glioma
Language english
Publication Year 2023
HGF-reported in Year 2023
ISSN (print) / ISBN 2375-2548
e-ISSN 2375-2548
Journal Science Advances
Quellenangaben Volume: 9, Issue: 43, Pages: , Article Number: eadi8986 Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place Washington, DC [u.a.]
Reviewing status Peer reviewed
Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)
POF-Topic(s) 30205 - Bioengineering and Digital Health
Research field(s) Enabling and Novel Technologies
PSP Element(s) G-505800-001
Grants Friedrich-Baur-Stiftung
Verein zur Forderung von Wissenschaft und Forschung an der Medizinischen Fakultaet der LMU Munchen (WiFoMed)
DFG
Else Kroner-Fresenius-Stiftung
German Research Foundation)
Deutsche Forschungsgemeinschaft (DFG
DOI 10.1126/sciadv.adi8986
WOS ID 001142878200017
Scopus ID 85175279359
PubMed ID 37889970
Erfassungsdatum 2023-11-28
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