Molecular Imaging of Fibrin Deposition in Deep Vein Thrombosis Using Fibrin-Targeted Near-Infrared Fluorescence
| Autor: | Tetsuya Hara, Ralph Weissleder, Brijesh Bhayana, Guillermo J. Tearney, Jason R. McCarthy, Ashok Khatri, Chase W. Kessinger, Brian Thompson, Farouc A. Jaffer, Charles P. Lin |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Pathology
Indoles 030204 cardiovascular system & hematology Ferric Compounds chemistry.chemical_compound Mice 0302 clinical medicine Fluorescence microscope Tissue Distribution Venous Thrombosis 0303 health sciences Microscopy Confocal Spectroscopy Near-Infrared biology medicine.diagnostic_test Thrombosis Imaging agent 3. Good health Molecular Imaging Radiology Nuclear Medicine and imaging Injections Intravenous fluorescence Cardiology and Cardiovascular Medicine Oligopeptides Half-Life medicine.medical_specialty Fluorophore Fibrin 03 medical and health sciences optical imaging Chlorides In vivo medicine Animals Humans Radiology Nuclear Medicine and imaging cardiovascular diseases Radionuclide Imaging 030304 developmental biology Fluorescent Dyes business.industry Magnetic resonance imaging Phlebography Femoral Vein medicine.disease Mice Inbred C57BL Disease Models Animal chemistry Microscopy Fluorescence biology.protein Molecular imaging business Tomography X-Ray Computed DVT |
| Zdroj: | JACC: Cardiovascular Imaging. 5(6):607-615 |
| ISSN: | 1936-878X |
| DOI: | 10.1016/j.jcmg.2012.01.017 |
| Popis: | ObjectivesThe goal of this study was to develop and validate a new fibrin-targeted imaging agent that enables high-resolution near-infrared fluorescence (NIRF) imaging of deep vein thrombosis (DVT).BackgroundNIRF imaging of fibrin could enable highly sensitive and noninvasive molecular imaging of thrombosis syndromes in vivo.MethodsA fibrin-targeted peptide was conjugated to a near-infrared fluorophore Cy7, termed FTP11-Cy7. The NIRF peptide is based on a fibrin-specific imaging agent that has completed Phase II clinical magnetic resonance imaging trials. In vitro binding of FTP11-Cy7 to human plasma clots was assessed by using fluorescence reflectance imaging. Next, FTP11-Cy7 was intravenously injected in mice with femoral DVT induced by topical 7.5% ferric chloride treatment. Intravital fluorescence microscopy and noninvasive fluorescence molecular tomography–computed tomography were performed in 32 mice with DVT, followed by histological analyses.ResultsIn vitro human clot-binding analyses showed a 6-fold higher NIRF clot target-to-background ratio (TBR) of FTP11-Cy7 than free Cy7 (6.3 ± 0.34 vs. 1.2 ± 0.03; p < 0.0001). The thrombus TBR of acute and subacute femoral DVT with FTP11-Cy7 obtained by using intravital fluorescence microscopy was >400% higher than control free Cy7. Binding of FTP11-Cy7 to thrombi was blocked by a 100-fold excess of unlabeled competitor peptide both in vitro and in vivo (p < 0.001 for each). Histological analyses confirmed that FTP11-Cy7 specifically accumulated in thrombi. Noninvasive fluorescence molecular tomography–computed tomography imaging of fibrin in jugular DVT demonstrated strong NIRF signal in thrombi compared with sham-operated jugular veins (mean TBR 3.5 ± 0.7 vs. 1.5 ± 0.3; p < 0.05).ConclusionsThe fibrin-targeted NIRF agent FTP11-Cy7 was shown to avidly and specifically bind human and murine thrombi, and enable sensitive, multimodal intravital and noninvasive NIRF molecular imaging detection of acute and subacute murine DVT in vivo. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|