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4. Multimodal Molecular Imaging of the Tumour Microenvironment

Author

Foray, Claudia, Barca, Cristina, Backhaus, Philipp, Schelhaas, Sonja, Winkeler, Alexandra, Viel, Thomas, Schäfers, Michael, Grauer, Oliver, Jacobs, Andreas H., Zinnhardt, Bastian, Crusio, Wim E., Series Editor, Dong, Haidong, Series Editor, Lambris, John D., Series Editor, Radeke, Heinfried H., Series Editor, Rezaei, Nima, Series Editor, Xiao, Junjie, Series Editor, and Birbrair, Alexander, editor

Published
2020
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7. Contributors

Author

Aarntzen, Erik, primary, Achilefu, Samuel, additional, Akam, Eman A., additional, Albaghdadi, Mazen, additional, Beer, Ambros J., additional, Bharti, Santosh, additional, Bhujwalla, Zaver M., additional, Bischof, Gérard N., additional, Biswal, Sandip, additional, Boss, Marti, additional, Botnar, René M., additional, Brinson, Zabecca, additional, Brom, Maarten, additional, Buitinga, Mijke, additional, Bulte, Jeff W.M., additional, Caravan, Peter, additional, Chan, Heang-Ping, additional, Chandy, Mark, additional, Chaney, Aisling M., additional, Chen, Delphine L., additional, Chen, Xiaoyuan (Shawn), additional, Chenevert, Thomas L., additional, Coughlin, Jennifer M., additional, Covington, Matthew F., additional, Cumming, Paul, additional, Daldrup-Link, Heike E., additional, Deal, Emily M., additional, de Galan, Bastiaan, additional, Derlin, Thorsten, additional, Dewhirst, Mark W., additional, Di Paolo, Arianna, additional, Drzezga, Alexander, additional, Du, Yong, additional, Thi-Quynh Duong, Mai, additional, Ehman, Richard L., additional, Eriksson, Olof, additional, Galli, Filippo, additional, Gatenby, Robert A., additional, Gelovani, Juri, additional, Giehl, Kathrin, additional, Giger, Maryellen L., additional, Goel, Reema, additional, Gold, Garry, additional, Gotthardt, Martin, additional, Graham, Michael M., additional, Gropler, Robert J., additional, Gründer, Gerhard, additional, Gulhane, Avanti, additional, Hadjiiski, Lubomir, additional, Hajhosseiny, Reza, additional, Hammoud, Dima A., additional, Helfer, Brooke M., additional, Hicks, Rodney J., additional, Higuchi, Takahiro, additional, Hoffman, John M., additional, Honer, Michael, additional, Huang, Sung-Cheng (Henry), additional, Hung, Jessica, additional, Hwang, Do Won, additional, Jackson, Isaac M., additional, Jacobs, Andreas H., additional, Jaffer, Farouc A., additional, Jain, Sanjay K., additional, James, Michelle L., additional, Jansen, Tom, additional, Johansson, Lars, additional, Joosten, Lieke, additional, Kakkad, Samata, additional, Kamson, David, additional, Kang, Sae-Ryung, additional, Kelly, Kimberly A., additional, Knopp, Michelle I., additional, Knopp, Michael V., additional, Kogan, Feliks, additional, Krishnamachary, Balaji, additional, Künnecke, Basil, additional, Lee, Dong Soo, additional, Libby, Peter, additional, Luker, Gary D., additional, Luker, Kathryn E., additional, Makowski, Marcus R., additional, Mankoff, David A., additional, Massoud, Tarik F., additional, Meyer, Charles R., additional, Miller, Zach, additional, Min, Jung-Joon, additional, Mondal, Suman B., additional, Montesi, Sydney B., additional, Navin, Patrick J., additional, Nekolla, Stephan G., additional, Niu, Gang, additional, Notohamiprodjo, Susan, additional, Ordoñez, Alvaro A., additional, Osborn, Eric A., additional, Pacheco-Torres, Jesus, additional, Pagano, Gennaro, additional, Palmer, Gregory M., additional, Paulmurugan, Ramasamy, additional, Penet, Marie-France, additional, Phinikaridou, Alkystis, additional, Pomper, Martin G., additional, Prieto, Claudia, additional, Qi, Haikun, additional, Raghunand, Natarajan, additional, Ramar, Thangam, additional, Reynolds, Fred, additional, Ropella-Panagis, Kathleen, additional, Ross, Brian D., additional, Rowe, Steven P., additional, Rudin, Markus, additional, Sadaghiani, Mohammad S., additional, Sager, Hendrik, additional, Samala, Ravi, additional, Saraste, Antti, additional, Schelhaas, Sonja, additional, Schwaiger, Markus, additional, Schwarz, Sally W., additional, Seiberlich, Nicole, additional, Shapiro, Mikhail G., additional, Shim, Hyunsuk, additional, Signore, Alberto, additional, Solnes, Lilja B., additional, Suh, Minseok, additional, Tsien, Christina, additional, van Eimeren, Thilo, additional, Varasteh, Zohreh, additional, Venkatesh, Sudhakar Kundapur, additional, Viel, Thomas, additional, Waerzeggers, Yannic, additional, Wahl, Richard L., additional, Weber, Wolfgang, additional, Werner, Rudolf A., additional, Winkeler, Alexandra, additional, Wong, Dean F., additional, Wright, Chadwick L., additional, Wu, Anna M., additional, Wu, Joseph C., additional, Yoon, Daehyun, additional, You, Sung-Hwan, additional, Yuan, Chun, additional, Yuan, Hong, additional, Zanzonico, Pat, additional, Zhao, Xue-Qiao, additional, Zhou, Iris Y., additional, and Zinnhardt, Bastian, additional

Published
2021
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10. Imaging in Neurooncology

Author

Waerzeggers, Yannic, Zinnhardt, Bastian, Winkeler, Alexandra, Monfared, Parisa, Schelhaas, Sonja, Viel, Thomas, Jacobs, Andreas H., Kiessling, Fabian, editor, Pichler, Bernd J., editor, and Hauff, Peter, editor

Published
2017
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13. Supplementary Figure Legends from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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15. Suppl. Fig. 3: Illustration of the applied thresholding. from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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17. Suppl. Fig. 1: Experimental design. from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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18. Data from Gemcitabine Mechanism of Action Confounds Early Assessment of Treatment Response by 3′-Deoxy-3′-[18F]Fluorothymidine in Preclinical Models of Lung Cancer

Author

Schelhaas, Sonja, primary, Held, Annelena, primary, Wachsmuth, Lydia, primary, Hermann, Sven, primary, Honess, Davina J., primary, Heinzmann, Kathrin, primary, Smith, Donna-Michelle, primary, Griffiths, John R., primary, Faber, Cornelius, primary, and Jacobs, Andreas H., primary

Published
2023
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20. Suppl. Fig. 2: Workflow of imaging data co-registration. from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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23. Data from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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25. Suppl. Fig. 4: Influence of imaging sequence. from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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26. Suppl. Fig. 5: Assessment of intra-rater reproducibility of the volumetric relation of [18F]DPA-714 and [18F]FET. from Combined PET Imaging of the Inflammatory Tumor Microenvironment Identifies Margins of Unique Radiotracer Uptake

Author

Zinnhardt, Bastian, primary, Pigeon, Hayet, primary, Thézé, Benoit, primary, Viel, Thomas, primary, Wachsmuth, Lydia, primary, Fricke, Inga B., primary, Schelhaas, Sonja, primary, Honold, Lisa, primary, Schwegmann, Katrin, primary, Wagner, Stefan, primary, Faust, Andreas, primary, Faber, Cornelius, primary, Kuhlmann, Michael T., primary, Hermann, Sven, primary, Schäfers, Michael, primary, Winkeler, Alexandra, primary, and Jacobs, Andreas H., primary

Published
2023
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32. Imaging of the calcium activated potassium channel 3.1 (KCa3.1) in vivo using a senicapoc‐derived positron emission tomography tracer

Author

Konken, Christian P., primary, Heßling, Kathrin, additional, Thale, Insa, additional, Schelhaas, Sonja, additional, Dabel, Jennifer, additional, Maskri, Sarah, additional, Bulk, Etmar, additional, Budde, Thomas, additional, Koch, Oliver, additional, Schwab, Albrecht, additional, Schäfers, Michael, additional, and Wünsch, Bernhard, additional

Published
2022
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33. Voxel-Based Analysis of the Relation of 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET and Diffusion-Weighted (DW) MR Signals in Subcutaneous Tumor Xenografts Does Not Reveal a Direct Spatial Relation of These Two Parameters

Author

Schelhaas, Sonja, primary, Frohwein, Lynn Johann, additional, Wachsmuth, Lydia, additional, Hermann, Sven, additional, Faber, Cornelius, additional, Schäfers, Klaus P., additional, and Jacobs, Andreas H., additional

Published
2021
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34. Synthesis and biological evaluation of PET tracers designed for imaging of calcium activated potassium channel 3.1 (KCa3.1) channels in vivo

Author

Brömmel, Kathrin, Konken, Christian Paul, Börgel, Frederik, Obeng-Darko, Henry, Schelhaas, Sonja, Bulk, Etmar Michael, Budde, Thomas, Schwab, Albrecht, Schäfers, Michael, Wünsch, Bernhard, and Universitäts- und Landesbibliothek Münster

Subjects
610 Medicine and health, Medicine and health, ddc:610
Abstract

Expression of the Ca2+ activated potassium channel 3.1 (KCa3.1) channel (also known as the Gàrdos channel) is dysregulated in many tumor entities and has predictive power with respect to patient survival. Therefore, a positron emission tomography (PET) tracer targeting this ion channel could serve as a potential diagnostic tool by imaging the KCa3.1 channel in vivo. It was envisaged to synthesize [18F]senicapoc ([18F]1) since senicapoc (1) shows high affinity and excellent selectivity towards the KCa3.1 channels. Because problems occurred during 18F-fluorination, the [18F]fluoroethoxy senicapoc derivative [18F]28 was synthesized to generate an alternative PET tracer targeting the KCa3.1 channel. Inhibition of the KCa3.1 channel by 28 was confirmed by patch clamp experiments. In vitro stability in mouse and human serum was shown for 28. Furthermore, biodistribution experiments in wild type mice were performed. Since [18F]fluoride was detected in vivo after application of [18F]28, an in vitro metabolism study was conducted. A potential degradation route of fluoroethoxy derivatives in vivo was found which in general should be taken into account when designing new PET tracers for different targets with a [18F]fluoroethoxy moiety as well as when using the popular prosthetic group [18F]fluoroethyl tosylate for the alkylation of phenols., Finanziert durch den Open-Access-Publikationsfonds der Westfälischen Wilhelms-Universität Münster (WWU Münster).

Published
2021
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40. Voxel-Based Analysis of the Relation of 3′-Deoxy-3′-[18F]fluorothymidine ([18F]FLT) PET and Diffusion-Weighted (DW) MR Signals in Subcutaneous Tumor Xenografts Does Not Reveal a Direct Spatial Relation of These Two Parameters

Author

Schelhaas, Sonja, Frohwein, Lynn Johann, Wachsmuth, Lydia, Hermann, Sven, Faber, Cornelius, Schäfers, Klaus P., and Jacobs, Andreas H.

Abstract

Purpose: Multimodal molecular imaging allows a direct coregistration of different images, facilitating analysis of the spatial relation of various imaging parameters. Here, we further explored the relation of proliferation, as measured by [18F]FLT PET, and water diffusion, as an indicator of cellular density and cell death, as measured by diffusion-weighted (DW) MRI, in preclinical tumor models. We expected these parameters to be negatively related, as highly proliferative tissue should have a higher density of cells, hampering free water diffusion. Procedures: Nude mice subcutaneously inoculated with either lung cancer cells (n = 11 A549 tumors, n = 20 H1975 tumors) or colorectal cancer cells (n = 13 Colo205 tumors) were imaged with [18F]FLT PET and DW-MRI using a multimodal bed, which was transferred from one instrument to the other within the same imaging session. Fiducial markers allowed coregistration of the images. An automatic post-processing was developed in MATLAB handling the spatial registration of DW-MRI (measured as apparent diffusion coefficient, ADC) and [18F]FLT image data and subsequent voxel-wise analysis of regions of interest (ROIs) in the tumor. Results: Analyses were conducted on a total of 76 datasets, comprising a median of 2890 data points (ranging from 81 to 13,597). Scatterplots showing [18F]FLT vs. ADC values displayed various grades of relations (Pearson correlation coefficient (PCC) varied from − 0.58 to 0.49, median: -0.07). When relating PCC to tumor volume (median: 46 mm3, range: 3 mm3 to 584 mm3), lung tumors tended to have a more pronounced negative spatial relation of [18F]FLT and ADC with increasing tumor size. However, due to the low number of large tumors (> ~ 200 mm3), this conclusion has to be treated with caution. Conclusions: A spatial relation of water diffusion, as measured by DW-MRI, and cellular proliferation, as measured by [18F]FLT PET, cannot be detected in the experimental datasets investigated in this study. [ABSTRACT FROM AUTHOR]

Published
2022
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41. Synthesis and biological evaluation of PET tracers designed for imaging of calcium activated potassium channel 3.1 (KCa3.1) channels in vivo

Author

Brömmel, Kathrin, primary, Konken, Christian Paul, additional, Börgel, Frederik, additional, Obeng-Darko, Henry, additional, Schelhaas, Sonja, additional, Bulk, Etmar, additional, Budde, Thomas, additional, Schwab, Albrecht, additional, Schäfers, Michael, additional, and Wünsch, Bernhard, additional

Published
2021
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43. Thymidine Metabolism as a Confounding Factor for 3′-Deoxy-3′-18F-Fluorothymidine Uptake After Therapy in a Colorectal Cancer Model

Author

Ralph, Sinkus, Schelhaas, Sonja, Wachsmuth, Lydia, Hermann, Sven, Rieder, Natascha, Heller, Astrid, Heinzmann, Kathrin, Honess, Davina, Smith, Donna-Michelle, Fricke, Inga, Just, Nathalie, Doblas, Sabrina, Sinkus, Ralph, Döring, Christian, Schäfers, Klaus, Griffiths, John, Faber, Cornelius, Schneider, Richard, Aboagye, Eric, Jacobs, Andreas, Griffiths, John [0000-0001-7369-6836], Apollo - University of Cambridge Repository, Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), and Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Colorectal cancer, [SDV.IB.MN]Life Sciences [q-bio]/Bioengineering/Nuclear medicine, Animal Imaging, 03 medical and health sciences, 0302 clinical medicine, DW-MRI, FOLFOX, small animal imaging, Combination cancer therapy, Medicine, Radiology, Nuclear Medicine and imaging, [18F]FLT, Thymidine kinase 1, ComputingMilieux_MISCELLANEOUS, business.industry, Oncology: GI, Cancer, 1103 Clinical Sciences, Combination chemotherapy, medicine.disease, digestive system diseases, 3. Good health, Oxaliplatin, Nuclear Medicine & Medical Imaging, PET, 030104 developmental biology, combination cancer therapy, 030220 oncology & carcinogenesis, Cancer research, business, Ex vivo, medicine.drug
Abstract

Non-invasive monitoring of tumor therapy response helps in developing personalized treatment strategies. Here, we performed sequential positron emission tomography (PET) and diffusion-weighted magnetic resonance imaging (DW-MRI) to evaluate changes induced by a FOLFOX-like combination chemotherapy in colorectal cancer (CRC) xenografts, to identify the cellular and molecular determinants of these imaging biomarkers. Methods: Tumor bearing CD1 nude mice, engrafted with FOLFOX-sensitive Colo205 CRC xenografts, were treated with FOLFOX (5 fluorouracil, leucovorin and oxaliplatin) in weekly intervals. On d1, d2, d6, d9 and d13 of therapy, tumors were assessed by in vivo imaging and ex vivo analyses. In addition, HCT116 xenografts, which did not respond to the FOLFOX treatment, were imaged on d1 of therapy. Results: In Colo205 xenografts, FOLFOX induced a profound increase in uptake of the proliferation PET tracer 3'-deoxy-3'-[18F]fluorothymidine ([18F]FLT), which was accompanied by increases in markers for proliferation (Ki67, TK1) and for activated DNA damage response (DDR; γH2AX), whereas the effect on cell death was minimal. As tracer uptake was unaltered in the HCT116 model, these changes appear to be specific for tumor response. Conclusion: We demonstrate that [18F]FLT PET can non-invasively monitor molecular alterations induced by a cancer treatment, including thymidine metabolism and DDR. The cellular or imaging changes may not, however, be directly related to therapy response as assessed by volumetric measurements.

Published
2018

44. Extracellular Vesicle Transfer from Endothelial Cells Drives VE-Cadherin Expression in Breast Cancer Cells, Thereby Causing Heterotypic Cell Contacts

Author

Rezaei, Maryam, primary, Martins Cavaco, Ana C., additional, Stehling, Martin, additional, Nottebaum, Astrid, additional, Brockhaus, Katrin, additional, Caliandro, Michele F., additional, Schelhaas, Sonja, additional, Schmalbein, Felix, additional, Vestweber, Dietmar, additional, and Eble, Johannes A., additional

Published
2020
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46. EZH2 Inhibition in Ewing Sarcoma Upregulates GD2 Expression for Targeting with Gene-Modified T Cells

Author

Kailayangiri, Sareetha, primary, Altvater, Bianca, additional, Lesch, Stefanie, additional, Balbach, Sebastian, additional, Göttlich, Claudia, additional, Kühnemundt, Johanna, additional, Mikesch, Jan-Henrik, additional, Schelhaas, Sonja, additional, Jamitzky, Silke, additional, Meltzer, Jutta, additional, Farwick, Nicole, additional, Greune, Lea, additional, Fluegge, Maike, additional, Kerl, Kornelius, additional, Lode, Holger N., additional, Siebert, Nikolai, additional, Müller, Ingo, additional, Walles, Heike, additional, Hartmann, Wolfgang, additional, and Rossig, Claudia, additional

Published
2019
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49. In vivo bioluminescence imaging of neurogenesis: the role of the blood brain barrier in an experimental model of Parkinson's disease

Author

Fricke, Inga B, Schelhaas, Sonja, Zinnhardt, Bastian, Viel, Thomas, Hermann, Svenn, Couillard-Deprés, Sébastien, and Jacobs, Andreas H

Subjects
nervous system, Doublecortin, Magnetic Resonance, Neurodegeneration, Optical Imaging, Substrate Delivery
Abstract

Bioluminescence imaging in transgenic mice expressing firefly luciferase in Doublecortin+ (Dcx) neuroblasts might serve as a powerful tool to study the role of neurogenesis in models of brain injury and neurodegeneration using non-invasive, longitudinal in vivo imaging. Therefore, we aimed to use BLI in B6(Cg)-Tyrc-2J/J Dcx-Luc (Doublecortin-Luciferase, Dcx-Luc) mice to investigate its suitability to assess neurogenesis in a unilateral injection model of Parkinson's disease. We further aimed to assess the blood brain barrier leakage associated with the intranigral 6-OHDA injection to evaluate its impact on substrate delivery and bioluminescence signal intensity. 2 weeks after lesion, we observed an increase in bioluminescence signal in the ipsilateral hippocampal region in both, 6-OHDA and vehicle injected Dcx-Luc mice. At the same time, no corresponding increase in Dcx+ neuroblast numbers could be observed in the dentate gyrus of C57Bl6 mice. Blood brain barrier leakage was observed in the hippocampal region and in the degenerating substantia nigra of C57Bl6 mice in vivo using T1 weighted Magnetic Resonance Imaging with Gadovist® and ex vivo using Evans Blue Fluorescence Reflectance Imaging and mouse Immunoglobulin G staining. Our data suggests a BLI signal dependency on blood brain barrier permeability, underlining a major pitfall of substrate/tracer dependent imaging in invasive disease models.

Published
2017

50. Combined PET imaging of the inflammatory tumor microenvironment identifies margins of unique radiotracer uptake

Author

Zinnhardt, Bastian, Pigeon, Hayet, Thézé, Benoit, Viel, Thomas, Wachstmuth, Lydia, Fricke, Inga Berit, Schelhaas, Sonja, Honold, Lisa, Schwegmann, Katrin, Wagner, Stefan, Faust, Andreas, Faber, Cornelius, Kuhlmann, Michael T, Hermann, Sven, Schäfers, Michael, Winkeler, Alexandra, and Jacobs, Andreas H

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, non-invasive imaging by positron emission tomography (PET) with [18F]DPA-714 (TSPO) and [18F]BR-351 (MMP) was used for 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 magnetic resonance imaging (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 1.4-1.7 fold with [18F]FET showing the biggest volume as depicted by a thresholding-based, volumes of interest (VOI) 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 (MMPs) matched with histology. Glioma-associated microglia/macrophages (GAM) were identified as TSPO and MMP sources. Multi-tracer and multi-modal molecular imaging approaches may allow us to gain important insights into glioma-associated inflammation (GAM, MMP). Moreover, this non-invasive technique enables characterization of the glioma microenvironment with respect to the disease-driving cellular compartments at the various disease stages.

Published
2017

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