Theranostics 2018; 8(10):2603-2620. doi:10.7150/thno.24128

Review

In vivo imaging biomarkers of neuroinflammation in the development and assessment of stroke therapies - towards clinical translation

Bastian Zinnhardt1,2,3,4,6✉, Maximilian Wiesmann5, Lisa Honold1*, Cristina Barca1,4, Michael Schäfers1,3,6, Amanda J Kiliaan5, Andreas H Jacobs1,2,3,4,7✉

1. European Institute for Molecular Imaging (EIMI), Westfälische Wilhelms University Münster, Münster, Germany
2. EU 7 th FP Programme “Imaging Inflammation in Neurodegenerative Diseases (INMiND)”
3. Cells in Motion (CiM) Cluster of Excellence, University of Münster, Münster, Germany
4. PET Imaging in Drug Design and Development (PET3D)
5. Department of Anatomy, Radboud university medical center, Donders Institute for Brain, Cognition & Behaviour, Nijmegen, The Netherlands
6. Department of Nuclear Medicine, Universitätsklinikum Münster, Münster, Germany
7. Department of Geriatrics, Johanniter Hospital, Evangelische Kliniken, Bonn, Germany
* Current address: Center for Systems Biology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA

Abstract

Modulation of the inflammatory microenvironment after stroke opens a new avenue for the development of novel neurorestorative therapies in stroke. Understanding the spatio-temporal profile of (neuro-)inflammatory imaging biomarkers in detail thereby represents a crucial factor in the development and application of immunomodulatory therapies. The early integration of quantitative molecular imaging biomarkers in stroke drug development may provide key information about (i) early diagnosis and follow-up, (ii) spatio-temporal drug-target engagement (pharmacodynamic biomarker), (iii) differentiation of responders and non-responders in the patient cohort (inclusion/exclusion criteria; predictive biomarkers), and (iv) the mechanism of action. The use of targeted imaging biomarkers for may thus allow clinicians to decipher the profile of patient-specific inflammatory activity and the development of patient-tailored strategies for immunomodulatory and neuro-restorative therapies in stroke. Here, we highlight the recent developments in preclinical and clinical molecular imaging biomarkers of neuroinflammation (endothelial markers, microglia, MMPs, cell labeling, future developments) in stroke and outline how imaging biomarkers can be used in overcoming current translational roadblocks and attrition in order to advance new immunomodulatory compounds within the clinical pipeline.

Keywords: Neuroinflammation, Stroke, Imaging, Microglia, TSPO, Matrix Metalloproteinases, Brain-gut axis

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How to cite this article:
Zinnhardt B, Wiesmann M, Honold L, Barca C, Schäfers M, Kiliaan AJ, Jacobs AH. In vivo imaging biomarkers of neuroinflammation in the development and assessment of stroke therapies - towards clinical translation. Theranostics 2018; 8(10):2603-2620. doi:10.7150/thno.24128. Available from http://www.thno.org/v08p2603.htm