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Imaging temozolomide-induced changes in the myeloid glioma microenvironment
- Source :
- Theranostics, Theranostics 11 (2021): 2020–2033. doi:10.7150/thno.47269, info:cnr-pdr/source/autori:Foray, Claudia; Valtorta, Silvia; Barca, Cristina; Winkeler, Alexandra; Roll, Wolfgang; Muether, Michael; Wagner, Stefan; Gardner, Miranda L.; Hermann, Sven; Schaefers, Michael; Grauer, Oliver Martin; Moresco, Rosa Maria; Zinnhardt, Bastian; Jacobs, Andreas H./titolo:Imaging temozolomide-induced changes in the myeloid glioma microenvironment/doi:10.7150%2Fthno.47269/rivista:Theranostics/anno:2021/pagina_da:2020/pagina_a:2033/intervallo_pagine:2020–2033/volume:11
- Publication Year :
- 2021
- Publisher :
- Ivyspring International Publisher, 2021.
-
Abstract
- 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.
- Subjects :
- 0301 basic medicine
Myeloid
[F-18]DPA-714
Medicine (miscellaneous)
Apoptosis
temozolomide
Mice
03 medical and health sciences
0302 clinical medicine
Immune system
In vivo
Glioma
[F-18]FET
Image Processing, Computer-Assisted
Tumor Cells, Cultured
Tumor Microenvironment
medicine
Animals
Humans
Antineoplastic Agents, Alkylating
Pharmacology, Toxicology and Pharmaceutics (miscellaneous)
Cell Proliferation
Tumor microenvironment
Temozolomide
Microglia
Brain Neoplasms
Chemistry
F]FET
glioblastoma
[18F]FET
F]DPA-714
medicine.disease
Xenograft Model Antitumor Assays
Tumor Burden
GAMM
030104 developmental biology
medicine.anatomical_structure
Tumor progression
[18F]DPA-714
Positron-Emission Tomography
Cancer research
Female
[
TSPO
030217 neurology & neurosurgery
Research Paper
medicine.drug
Subjects
Details
- ISSN :
- 18387640
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Theranostics
- Accession number :
- edsair.doi.dedup.....0e0589083ac7cf511fc6aa4ff0b94e23