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Abstract

The tumor microenvironment is highly heterogeneous. For gliomas, the tumor-associated inflammatory response is pivotal to support growth and invasion. Factors of glioma growth, inflammation, and invasion, such as the translocator protein (TSPO) and matrix metalloproteinases (MMP), may serve as specific imaging biomarkers of the glioma microenvironment. In this study, noninvasive imaging by PET with [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) was used for the assessment of localization and quantification of the expression of TSPO and MMP. Imaging was performed in addition to established clinical imaging biomarker of active tumor volume ([18F]FET) in conjunction with MRI. We hypothesized that each imaging biomarker revealed distinct areas of the heterogeneous glioma tissue in a mouse model of human glioma. Tracers were found to be increased 1.4- to 1.7-fold, with [18F]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest analysis. Tumor areas, which could not be detected by a single tracer and/or MRI parameter alone, were measured. Specific compartments of [18F]DPA-714 (14%) and [18F]BR-351 (11%) volumes along the tumor rim could be identified. [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multitracer and multimodal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this noninvasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages.  

Author information​

Zinnhardt B1, Pigeon H2, Thézé B2, Viel T3,4, Wachsmuth L5, Fricke IB3, Schelhaas S3, Honold L3, Schwegmann K3, Wagner S6, Faust A3, Faber C5,7, Kuhlmann MT3, Hermann S3,7, Schäfers M3,6,7, Winkeler A2, Jacobs AH3,7,8.

1 European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-University Münster, Münster, Germany. zinnhardt@wwu.de.

2 Imagerie Moléculaire In Vivo, Inserm, CEA, Univ. Paris Sud, CNRS, Université Paris Saclay, CEA - Service Hospitalier Frédéric Joliot, Orsay, France.

3 European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms-University Münster, Münster, Germany.

4 PARCC INSERM-U970, Université Paris Descartes, Paris, France.

5 Department of Clinical Radiology, University Hospital Münster, Münster, Germany.

6 Department of Nuclear Medicine, University Hospital Münster, Münster, Germany.

7 DFG EXC 1003 Cluster of Excellence 'Cells in Motion', University of Münster, Münster, Germany.

8 Department of Geriatrics, Johanniter Hospital, Evangelische Kliniken, Bonn, Germany.