Theranostics 2019; 9(25):7525-7536. doi:10.7150/thno.36264 This issue

Research Paper

A versatile imaging platform with fluorescence and CT imaging capabilities that detects myeloperoxidase activity and inflammation at different scales

Cuihua Wang1,2#, Benjamin Pulli1,2#, Negin Jalali Motlagh1,2, Anning Li1, Gregory R. Wojtkiewicz1, Stephan P. Schmidt1, Yue Wu1, Matthias W.G. Zeller1, John W. Chen1,2✉

1. Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, Boston, MA
2. Institute for Innovation in Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA
# Both authors contributed equally to this work

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wang C, Pulli B, Jalali Motlagh N, Li A, Wojtkiewicz GR, Schmidt SP, Wu Y, Zeller MWG, Chen JW. A versatile imaging platform with fluorescence and CT imaging capabilities that detects myeloperoxidase activity and inflammation at different scales. Theranostics 2019; 9(25):7525-7536. doi:10.7150/thno.36264. Available from https://www.thno.org/v09p7525.htm

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Abstract

Graphic abstract

Aberrant innate immune response drives the pathophysiology of many diseases. Myeloperoxidase (MPO) is a highly oxidative enzyme secreted by activated myeloid pro-inflammatory immune cells such as neutrophils and macrophages, and is a key mediator of the damaging innate immune response. Current technologies for detecting MPO activity in living organisms are sparse and suffer from any combination of low specificity, low tissue penetration, or low spatial resolution. We describe a versatile imaging platform to detect MPO activity using an activatable construct conjugated to a biotin moiety (MPO-activatable biotinylated sensor, MABS) that allows monitoring the innate immune response and its modulation at different scales and settings.

Methods: We designed and synthesized MABS that contains MPO-specific and biotin moieties, and validated its specificity and sensitivity combining with streptavidin-labeled fluorescent agent and gold nanoparticles imaging in vitro and in vivo in multiple mouse models of inflammation and infection, including Matrigel implant, dermatitis, cellulitis, cerebritis and complete Fraud's adjuvant (CFA)-induced inflammation.

Results: MABS MPO imaging non-invasively detected varying MPO concentrations, MPO inhibition, and MPO deficiency in vivo with high sensitivity and specificity. MABS can be used to obtain not only a fluorescence imaging agent, but also a CT imaging agent, conferring molecular activity information to a structural imaging modality. Importantly, using this method on tissue-sections, we found that MPO enzymatic activity does not always co-localize with MPO protein detected with conventional techniques (e.g., immunohistochemistry), underscoring the importance of monitoring enzymatic activity.

Conclusion: By choosing from different available secondary probes, MABS can be used to create systems suitable to investigate and image MPO activity at different scales and settings.

Keywords: myeloperoxidase, imaging platform, enzymatic activity, neutrophil extracellular traps.