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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)

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	Open Access Gold

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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

Corresponding Author

Keywords Tspo; Platform; Glioma

ISSN (print) / ISBN 2375-2548

e-ISSN 2375-2548

Journal Science Advances

Quellenangaben Volume: 9, Issue: 43, Article Number: eadi8986

Publisher American Association for the Advancement of Science (AAAS)

Publishing Place Washington, DC [u.a.]

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Institute for Tissue Engineering and Regenerative Medicine (ITERM)

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