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

Autor: Laura M Bartos, Sabrina V Kirchleitner, Zeynep Ilgin Kolabas, Stefanie Quach, Jens Blobner, Stephan A Mueller, Selin Ulukaya, Luciano Hoeher, Izabela Horvath, Karin Wind-Mark, Adrien Holzgreve, Viktoria C Ruf, Lukas Gold, Lea H Kunze, Sebastian T Kunte, Philipp Beumers, Melissa Antons, Artem Zatcepin, Nils Briel, Leonie Hoermann, Denise Messerer, Peter Bartenstein, Markus J Riemenschneider, Simon Lindner, Sibylle Ziegler, Jochen Herms, Stefan F Lichtenthaler, Ali Ertürk, Joerg C Tonn, Louisa von Baumgarten, Nathalie L Albert, Matthias Brendel
Rok vydání: 2023
Popis: Various cellular sources hamper interpretation of positron-emission-tomography (PET) biomarkers in the tumor microenvironment (TME). We developed immunomagnetic cell sorting afterin vivoradiotracer injection (scRadiotracing) in combination with 3D-histology via tissue clearing to dissect the cellular allocation of PET signals in the TME. In SB28 glioblastoma mice, translocator protein (TSPO) radiotracer uptake per tumor cell was higher compared to tumor-associated microglia/macrophages (TAMs). Cellular radiotracer uptake was validated by proteomics and confirmed forin vitrosamples of patients with glioblastoma. Regional agreement between PET signals and single cell tracer uptake predicted the individual cell distribution in 3D-histology. 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 complex PET signal sources and will serve to validate novel TAM-specific radioligands.
Databáze: OpenAIRE