Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution-Reference-Cited by-同舟云学术

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

Published:2023-10-27 Issue:43 Volume:9 Page:
ISSN:2375-2548
Container-title:Science Advances
language:en
Short-container-title:Sci. Adv.

Author:

Bartos Laura M.¹^ORCID,Kirchleitner Sabrina V.²^ORCID,Kolabas Zeynep Ilgin³⁴⁵^ORCID,Quach Stefanie²^ORCID,Beck Alexander⁶^ORCID,Lorenz Julia⁷^ORCID,Blobner Jens²,Mueller Stephan A.⁸⁹^ORCID,Ulukaya Selin³¹⁰^ORCID,Hoeher Luciano³,Horvath Izabela³¹¹^ORCID,Wind-Mark Karin¹^ORCID,Holzgreve Adrien¹^ORCID,Ruf Viktoria C.⁶^ORCID,Gold Lukas¹^ORCID,Kunze Lea H.¹^ORCID,Kunte Sebastian T.¹,Beumers Philipp¹,Park Ha Eun¹^ORCID,Antons Melissa¹^ORCID,Zatcepin Artem¹⁹^ORCID,Briel Nils⁶⁹^ORCID,Hoermann Leonie¹,Schaefer Rebecca¹^ORCID,Messerer Denise¹²,Bartenstein Peter¹¹³,Riemenschneider Markus J.⁷,Lindner Simon¹¹³^ORCID,Ziegler Sibylle¹,Herms Jochen⁶⁹¹³,Lichtenthaler Stefan F.⁸⁹¹³^ORCID,Ertürk Ali³⁴⁵¹³,Tonn Joerg C.²¹⁴^ORCID,von Baumgarten Louisa²¹⁴,Albert Nathalie L.¹¹⁴¹⁵^ORCID,Brendel Matthias¹⁹¹³^ORCID

Affiliation:

1. Department of Nuclear Medicine, University Hospital of Munich, LMU Munich, Munich, Germany.

2. Department of Neurosurgery, University Hospital of Munich, LMU Munich, Munich, Germany.

3. Institute for Tissue Engineering and Regenerative Medicine (iTERM), Helmholtz Center, Neuherberg, Munich, Germany.

4. Institute for Stroke and Dementia Research (ISD), University Hospital of Munich, LMU Munich, Munich, Germany.

5. Graduate School of Systemic Neurosciences (GSN), Munich, Germany.

6. Center for Neuropathology and Prion Research, Faculty of Medicine, LMU Munich, Munich, Germany.

7. Department of Neuropathology, Regensburg University Hospital, Regensburg, Germany.

8. Neuroproteomics, School of Medicine, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.

9. DZNE–German Center for Neurodegenerative Diseases, Munich, Germany.

10. Faculty of Biology, Master of Science Program in Molecular and Cellular Biology, Ludwig-Maximilians-Universität München, Planegg, Germany.

11. School of Computation, Information and Technology (CIT), TUM, Boltzmannstr. 3, 85748 Garching, Germany.

12. Department of Cardiology, University Hospital of Munich, LMU Munich, Munich, Germany.

13. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany.

14. German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.

15. Bavarian Cancer Research Center (BZKF), Erlangen, Germany.

Abstract

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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

Link

https://www.science.org/doi/pdf/10.1126/sciadv.adi8986

Reference77 articles.

1. The updated landscape of tumor microenvironment and drug repurposing

2. Targeting the tumor microenvironment: removing obstruction to anticancer immune responses and immunotherapy

3. Potential PET tracers for imaging of tumor-associated macrophages

4. Whole-body CD8+ T cell visualization before and during cancer immunotherapy: a phase 1/2 trial

5. Primary brain and other central nervous system tumors in the United States (2014-2018): A summary of the CBTRUS statistical report for clinicians;Low J. T.;Neurooncol. Pract.,2022

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