RRC ID 54517
Author Huber VJ, Igarashi H, Ueki S, Terumitsu-Tsujita M, Nito C, Ohno K, Suzuki Y, Itoh K, Kwee IL, Nakada T.
Title Visualizing the Distribution of Matrix Metalloproteinases in Ischemic Brain Using In Vivo 19F-Magnetic Resonance Spectroscopic Imaging.
Journal Contrast Media Mol Imaging
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.
Volume 2019
Pages 8908943
Published 2019-1-6
DOI 10.1155/2019/8908943
PMID 30723388
PMC PMC6339703
MeSH Animals Blood-Brain Barrier / diagnostic imaging Blood-Brain Barrier / metabolism Brain Ischemia / diagnostic imaging* Brain Ischemia / metabolism* Fluorine-19 Magnetic Resonance Imaging / methods* Male Matrix Metalloproteinase 2 / metabolism Matrix Metalloproteinase 3 / metabolism Matrix Metalloproteinase 9 / metabolism Matrix Metalloproteinases / metabolism* Mice Mice, Inbred C57BL Mice, Knockout
IF 2.934
Times Cited 0
Mice RBRC00398