Evaluating magnetic resonance spectroscopy as a tool for monitoring therapeutic response of whole brain radiotherapy in a mouse model for breast-to-brain metastasis

  • Brain metastases are the most common intracranial tumor in adults and are associated with poor patient prognosis and median survival of only a few months. Treatment options for brain metastasis patients remain limited and largely depend on surgical resection, radio- and/or chemotherapy. The development and pre-clinical testing of novel therapeutic strategies require reliable experimental models and diagnostic tools that closely mimic technologies that are used in the clinic and reflect histopathological and biochemical changes that distinguish tumor progression from therapeutic response. In this study, we sought to test the applicability of magnetic resonance (MR) spectroscopy in combination with MR imaging to closely monitor therapeutic efficacy in a breast-to-brain metastasis model. Given the importance of radiotherapy as the standard of care for the majority of brain metastases patients, we chose to monitor the post-irradiation response by magnetic resonance spectroscopy (MRS) in combination with MR imaging (MRI) using a 7 Tesla small animal scanner. Radiation was applied as whole brain radiotherapy (WBRT) using the image-guided Small Animal Radiation Research Platform (SARRP). Here we describe alterations in different metabolites, including creatine and N-acetylaspartate, that are characteristic for brain metastases progression and lactate, which indicates hypoxia, while choline levels remained stable. Radiotherapy resulted in normalization of metabolite levels indicating tumor stasis or regression in response to treatment. Our data indicate that the use of MR spectroscopy in addition to MRI represents a valuable tool to closely monitor not only volumetrical but also metabolic changes during tumor progression and to evaluate therapeutic efficacy of intervention strategies. Adapting the analytical technology in brain metastasis models to those used in clinical settings will increase the translational significance of experimental evaluation and thus contribute to the advancement of pre-clinical assessment of novel therapeutic strategies to improve treatment options for brain metastases patients.

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Author:Woon Hyung Chae, Katja Anne NieselORCiDGND, Michael SchulzGND, Florian Klemm, Johanna A. Joyce, Marcus Prümmer, Boris Brill, Judith Bergs, Franz RödelORCiDGND, Ulrich PilatusORCiD, Lisa SevenichORCiDGND
Pubmed Id:https://pubmed.ncbi.nlm.nih.gov/31828043
Parent Title (English):Frontiers in oncology
Publisher:Frontiers Media
Place of publication:Lausanne
Contributor(s):Roger Bourne
Document Type:Article
Year of Completion:2019
Year of first Publication:2019
Publishing Institution:Universitätsbibliothek Johann Christian Senckenberg
Release Date:2020/02/03
Tag:brain metastases; magnetic resonance imaging; metabolites; pre-clinical models; radioresponse; radiotherapy; spectroscopy
Issue:Art. 1324
Page Number:14
First Page:1
Last Page:14
Copyright © 2019 Chae, Niesel, Schulz, Klemm, Joyce, Prümmer, Brill, Bergs, Rödel, Pilatus and Sevenich. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Institutes:Biowissenschaften / Biowissenschaften
Medizin / Medizin
Angeschlossene und kooperierende Institutionen / Georg-Speyer-Haus
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Licence (German):License LogoCreative Commons - Namensnennung 4.0