Activated Coagulation FXII: A Unique Target for In Vivo Molecular Imaging
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Le résumé fourni par la source
Background: Current clinical imaging of thromboembolic diseases often relies on indirect detection of thrombi, which may delay diagnosis and ultimately the institution of beneficial, potentially lifesaving treatment. Therefore, the development of targeting tools that facilitate the rapid, specific, and direct imaging of thrombi using molecular imaging is highly sought after. One potential molecular target is FXIIa (factor XIIa), which initiates the intrinsic coagulation pathway but also activates the kallikrein-kinin system, thereby initiating coagulation and inflammatory/immune responses. As FXII (factor XII) is dispensable for normal hemostasis, its activated form (FXIIa) represents an ideal molecular target for diagnostic and therapeutic approaches, the latter combining diagnosis/identification of thrombi and effective antithrombotic therapy. Methods: We conjugated an FXIIa-specific antibody, 3F7, to a near-infrared (NIR) fluorophore and demonstrated binding to FeCl 3 -induced carotid thrombosis with 3-dimensional fluorescence emission computed tomography/computed tomography and 2-dimensional fluorescence imaging. We further demonstrated ex vivo imaging of thromboplastin-induced pulmonary embolism and detection of FXIIa in human thrombi produced in vitro. Results: We demonstrated imaging of carotid thrombosis by fluorescence emission computed tomography/computed tomography and measured a significant fold increase in signal between healthy and control vessels from mice injected with 3F7-NIR compared with mice injected with nontargeted probe ( P =0.002) ex vivo. In a model of pulmonary embolism, we measured increased NIR signal in lungs from mice injected with 3F7-NIR compared with mice injected with nontargeted probe ( P =0.0008) and healthy lungs from mice injected with 3F7-NIR ( P =0.021). Conclusions: Overall, we demonstrate that FXIIa targeting is highly suitable for the specific detection of venous and arterial thrombi. This approach will allow direct, specific, and early imaging of thrombosis in preclinical imaging modalities and may facilitate monitoring of antithrombotic treatment in vivo.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Activated Coagulation FXII: A Unique Target for In Vivo Molecular Imaging
- Date Crossref
- 01/06/2023
- Éditeur
- Ovid Technologies (Wolters Kluwer Health)
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Baker Heart and Diabetes Institute pays non établi dans la noticeOrganisation à but non lucratif
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Monash University Department of Medicine pays non établi dans la noticeUniversité ou école supérieure
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The University of Melbourne Department of Cardiometabolic Health pays non établi dans la noticeUniversité ou école supérieure
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The Alfred Hospital pays non établi dans la noticeÉtablissement de santé
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CSL (United Kingdom) pays non établi dans la noticeEntreprise
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CSL (Australia) pays non établi dans la noticeEntreprise
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La Trobe University Department of Cardiovascular Research pays non établi dans la noticeUniversité ou école supérieure
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Atherothrombosis and Vascular Biology Laboratory (A.P.G.W. pays non établi dans la noticeStructure de recherche
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Molecular Imaging and Theranostics Laboratory (A.P.G.W. pays non établi dans la noticeStructure de recherche
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Clinical Haematology Department pays non établi dans la noticeÉtablissement de santé
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Ltd CSL pays non établi dans la noticeEntreprise
Baker Heart and Diabetes Institute, Department of Medicine — Monash University et Department of Cardiometabolic Health — The University of Melbourne, avec 8 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.