Deciphering sources of PET signals in the tumor microenvironment of glioblastoma at cellular resolution.
Journal
Science advances
ISSN: 2375-2548
Titre abrégé: Sci Adv
Pays: United States
ID NLM: 101653440
Informations de publication
Date de publication:
27 10 2023
27 10 2023
Historique:
medline:
30
10
2023
pubmed:
27
10
2023
entrez:
27
10
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37889970
doi: 10.1126/sciadv.adi8986
pmc: PMC10610915
doi:
Substances chimiques
Carrier Proteins
0
TSPO protein, human
0
Receptors, GABA
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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