Kim, Jeong-Yeon Ryu, Ju Hee Schellingerhout, Dawid Sun, In-Cheol Lee, Su-Kyoung Jeon, Sangmin Kim, Jiwon Kwon, Ick Chan Nahrendorf, Matthias Ahn, Cheol-Hee Kim, Kwangmeyung Kim, Dong-Eog 2024-01-20T06:34:06Z 2024-01-20T06:34:06Z 2021-09-05 2015-07 1838-7640 https://pubs.kist.re.kr/handle/201004/125271 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 C57BI/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. English IVYSPRING INT PUBL Direct Imaging of Cerebral Thromboemboli Using Computed Tomography and Fibrin-targeted Gold Nanoparticles Article 10.7150/thno.11679 1 THERANOSTICS, v.5, no.10, pp.1098 - 1114 THERANOSTICS 5 10 1098 1114 N scie scopus 000359472700005 2-s2.0-84945949477 Medicine, Research & Experimental Research & Experimental Medicine Article MYOCARDIAL-INFARCTION THROMBUS FORMATION ISCHEMIC-STROKE CONTRAST AGENT IN-VIVO THERAPY RESISTANCE MODELS direct thrombus imaging gold nanoparticles computed tomography cerebral infarction molecular imaging