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Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution.
Sci. Adv. 9:eadi8986 (2023)
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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Publikationstyp
Artikel: Journalartikel
Dokumenttyp
Wissenschaftlicher Artikel
Schlagwörter
Tspo; Platform; Glioma
ISSN (print) / ISBN
2375-2548
e-ISSN
2375-2548
Zeitschrift
Science Advances
Quellenangaben
Band: 9,
Heft: 43,
Artikelnummer: eadi8986
Verlag
American Association for the Advancement of Science (AAAS)
Verlagsort
Washington, DC [u.a.]
Nichtpatentliteratur
Publikationen
Begutachtungsstatus
Peer reviewed
Institut(e)
Institute for Tissue Engineering and Regenerative Medicine (ITERM)
Förderungen
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
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