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

Laura M BartosSabrina V KirchleitnerZeynep Ilgin KolabasStefanie LietkeAlexander BeckJulia LorenzJens BlobnerStephan A MüllerSelin UlukayaLuciano HoeherIzabela HorvathKarin Wind-MarkAdrien HolzgreveViktoria C RufLukas GoldLea Helena KunzeSebastian T KuntePhilipp BeumersHa Eun ParkMelissa AntonsArtem ZatcepinNils BrielLeonie HoermannRebecca SchaeferDenise MessererPeter BartensteinMarkus J RiemenschneiderSimon LindnerSibylle ZieglerJochen HermsStefan F LichtenthalerAli ErtürkJoerg-Christian TonnLouisa von BaumgartenNathalie L AlbertMatthias Brendel
Published in: Science advances (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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