Visualizing the Distribution of Matrix Metalloproteinases in Ischemic Brain Using In Vivo 19F-Magnetic Resonance Spectroscopic Imaging

Vincent J. Huber, Hironaka Igarashi, Satoshi Ueki, Mika Terumitsu-Tsujita, Chikako Nito, Ken Ohno, Yuji Suzuki, Kosuke Itoh, Ingrid Kwee, Tsutomu Nakada

Research output: Contribution to journalArticle

Abstract

Matrix metalloproteinases (MMPs) damage the neurovascular unit, promote the blood-brain barrier (BBB) disruption following ischemic stroke, and play essential roles in hemorrhagic transformation (HT), which is one of the most severe side effects of thrombolytic therapy. However, no biomarkers have presently been identified that can be used to track changes in the distribution of MMPs in the brain. Here, we developed a new 19F-molecular ligand, TGF-019, for visualizing the distribution of MMPs in vivo using 19F-magnetic resonance spectroscopic imaging (19F-MRSI). We demonstrated TGF-019 has sufficient sensitivity for the specific MMPs suspected in evoking HT during ischemic stroke, i.e., MMP2, MMP9, and MMP3. We then utilized it to assess those MMPs at 22 to 24 hours after experimental focal cerebral ischemia on MMP2-null mice, as well as wild-type mice with and without the systemic administration of the recombinant tissue plasminogen activator (rt-PA). The 19F-MRSI of TGN-019-administered mice showed high signal intensity within ischemic lesions that correlated with total MMP2 and MMP9 activity, which was confirmed by zymographic analysis of ischemic tissues. Based on the results of this study, 19F-MRSI following TGN-019 administration can be used to assess potential therapeutic strategies for ischemic stroke.

Original languageEnglish (US)
Article number8908943
JournalContrast Media and Molecular Imaging
Volume2019
DOIs
StatePublished - Jan 1 2019

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging

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    Huber, V. J., Igarashi, H., Ueki, S., Terumitsu-Tsujita, M., Nito, C., Ohno, K., Suzuki, Y., Itoh, K., Kwee, I., & Nakada, T. (2019). Visualizing the Distribution of Matrix Metalloproteinases in Ischemic Brain Using In Vivo 19F-Magnetic Resonance Spectroscopic Imaging. Contrast Media and Molecular Imaging, 2019, [8908943]. https://doi.org/10.1155/2019/8908943