Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles

Jeong Yeon Kim, Ju Hee Ryu, Dawid Schellingerhout, In Cheol Sun, Su Kyoung Lee, Sangmin Jeon, Jiwon Kim, Ick Chan Kwon, Matthias Nahrendorf, Cheol Hee Ahn, Kwang Meyung Kim, Dong Eog Kim

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Computed tomography (CT) is the current standard for time-critical decision-making in stroke patients, informing decisions on thrombolytic therapy with tissue plasminogen activator (tPA), which has a narrow therapeutic index. We aimed to develop a CT-based method to directly visualize cerebrovascular thrombi and guide thrombolytic therapy. Glycol-chitosan-coated gold nanoparticles (GC-AuNPs) were synthesized and conjugated to fibrin-targeting peptides, forming fib-GC-AuNP. This targeted imaging agent and non-targeted control agent were characterized in vitro and in vivo in C57Bl/6 mice (n = 107) with FeCl3-induced carotid thrombosis and/or embolic ischemic stroke. Fibrin-binding capacity was superior with fib-GC-AuNPs compared to GC-AuNPs, with thrombi visualized as high density on microCT (mCT). mCT imaging using fib-GC-AuNP allowed the prompt detection and quantification of cerebral thrombi, and monitoring of tPA-mediated thrombolytic effect, which reflected histological stroke outcome. Furthermore, recurrent thrombosis could be diagnosed by mCT without further nanoparticle administration for up to 3 weeks. fib-GC-AuNP-based direct cerebral thrombus imaging greatly enhance the value and information obtainable by regular CT, has multiple uses in basic / translational vascular research, and will likely allow personalized thrombolytic therapy in clinic by a) optimizing tPA-dosing to match thrombus burden, b) enabling the rational triage of patients to more radical therapies such as endovascular clot-retrieval, and c) potentially serving as a theranostic platform for targeted delivery of concurrent thrombolysis.

Original languageEnglish
Pages (from-to)1098-1114
Number of pages17
JournalTheranostics
Volume5
Issue number10
DOIs
Publication statusPublished - 2015
Externally publishedYes

Keywords

  • Cerebral infarction
  • Computed tomography
  • Direct thrombus imaging
  • Gold nanoparticles
  • Molecular imaging

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Pharmacology, Toxicology and Pharmaceutics (miscellaneous)

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  • Cite this

    Kim, J. Y., Ryu, J. H., Schellingerhout, D., Sun, I. C., Lee, S. K., Jeon, S., Kim, J., Kwon, I. C., Nahrendorf, M., Ahn, C. H., Kim, K. M., & Kim, D. E. (2015). Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles. Theranostics, 5(10), 1098-1114. https://doi.org/10.7150/thno.11679