Rationale: The heterogeneous nature of gliomas makes the development and application of novel treatments challenging. In particular, infiltrating myeloid cells play a role in tumor progression and therapy resistance. Hence, a detailed understanding of the dynamic interplay of tumor cells and immune cells in vivo is necessary. To investigate the complex interaction between tumor progression and therapy-induced changes in the myeloid immune component of the tumor microenvironment, we used a combination of [18F]FET (amino acid metabolism) and [18F]DPA-714 (TSPO, GAMMs, tumor cells, astrocytes, endothelial cells) PET/MRI together with immune-phenotyping. The aim of the study was to monitor temozolomide (TMZ) treatment response and therapy-induced changes in the inflammatory tumor microenvironment (TME). Methods: Eighteen NMRInu/nu mice orthotopically implanted with Gli36dEGFR cells underwent MRI and PET/CT scans before and after treatment with TMZ or DMSO (vehicle). Tumor-to-background (striatum) uptake ratios were calculated and areas of unique tracer uptake (FET vs. DPA) were determined using an atlas-based volumetric approach. Results: TMZ therapy significantly modified the spatial distribution and uptake of both tracers. [18F]FET uptake was significantly reduced after therapy (-53 ± 84%) accompanied by a significant decrease of tumor volume (-17 ± 6%). In contrast, a significant increase (61 ± 33%) of [18F]DPA-714 uptake was detected by TSPO imaging in specific areas of the tumor. Immunohistochemistry (IHC) validated the reduction in tumor volumes and further revealed the presence of reactive TSPO-expressing glioma-associated microglia/macrophages (GAMMs) in the TME. Conclusion: We confirm the efficiency of [18F]FET-PET for monitoring TMZ-treatment response and demonstrate that in vivo TSPO-PET performed with [18F]DPA-714 can be used to identify specific reactive areas of myeloid cell infiltration in the TME.
Foray, C., Valtorta, S., Barca, C., Winkeler, A., Roll, W., Muther, M., et al. (2021). Imaging temozolomide-induced changes in the myeloid glioma microenvironment. THERANOSTICS, 11(5 (1 January 2021)), 2020-2033.
|Citazione:||Foray, C., Valtorta, S., Barca, C., Winkeler, A., Roll, W., Muther, M., et al. (2021). Imaging temozolomide-induced changes in the myeloid glioma microenvironment. THERANOSTICS, 11(5 (1 January 2021)), 2020-2033.|
|Tipo:||Articolo in rivista - Articolo scientifico|
|Carattere della pubblicazione:||Scientifica|
|Presenza di un coautore afferente ad Istituzioni straniere:||Si|
|Titolo:||Imaging temozolomide-induced changes in the myeloid glioma microenvironment|
|Autori:||Foray, C; Valtorta, S; Barca, C; Winkeler, A; Roll, W; Muther, M; Wagner, S; Gardner, M; Hermann, S; Schafers, M; Grauer, O; Moresco, R; Zinnhardt, B; Jacobs, A|
|Data di pubblicazione:||2021|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.7150/thno.47269|
|Appare nelle tipologie:||01 - Articolo su rivista|