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Imaging temozolomide-induced changes in the myeloid glioma microenvironment.
Foray, Claudia; Valtorta, Silvia; Barca, Cristina; Winkeler, Alexandra; Roll, Wolfgang; Müther, Michael; Wagner, Stefan; Gardner, Miranda L; Hermann, Sven; Schäfers, Michael; Grauer, Oliver Martin; Moresco, Rosa Maria; Zinnhardt, Bastian; Jacobs, Andreas H.
Afiliación
  • Foray C; European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
  • Valtorta S; PET Imaging in Drug Design and Development (PET3D), Münster, Germany.
  • Barca C; Tecnomed Foundation and Medicine and Surgery Department, University of Milano-Bicocca, Milan, Italy.
  • Winkeler A; Experimental Imaging Center, IRCCS San Raffaele Scientific Institute, Milan, Italy.
  • Roll W; Institute of Molecular Bioimaging and Physiology (IBFM), CNR, Segrate (MI), Italy.
  • Müther M; European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
  • Wagner S; PET Imaging in Drug Design and Development (PET3D), Münster, Germany.
  • Gardner ML; Université Paris-Saclay, CEA, CNRS, Inserm, BioMaps, Orsay, France.
  • Hermann S; Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
  • Schäfers M; Department of Neurosurgery, University Hospital Münster, Münster, Germany.
  • Grauer OM; Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.
  • Moresco RM; Campus Chemical Instrument Center, Mass Spectrometry and Proteomics Facility (CCIC-MSP), The Ohio State University, Columbus, OH, United States.
  • Zinnhardt B; European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
  • Jacobs AH; European Institute for Molecular Imaging - EIMI, University of Münster, Münster, Germany.
Theranostics ; 11(5): 2020-2033, 2021.
Article en En | MEDLINE | ID: mdl-33500706
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Procesamiento de Imagen Asistido por Computador / Neoplasias Encefálicas / Antineoplásicos Alquilantes / Microambiente Tumoral / Temozolomida / Glioma Límite: Animals / Female / Humans Idioma: En Revista: Theranostics Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Australia
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Procesamiento de Imagen Asistido por Computador / Neoplasias Encefálicas / Antineoplásicos Alquilantes / Microambiente Tumoral / Temozolomida / Glioma Límite: Animals / Female / Humans Idioma: En Revista: Theranostics Año: 2021 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Australia