Aged venous thrombi: radioimmunoimaging with fibrin-specific monoclonal antibody.

Rosebrough, S F; Grossman, Zachary D.; McAfee, John G.; Kudryk, Bohdan J.; Subramanian, G.; Ritter-Hrncirik, Cathy A.; Witanowski, Larry S.; Tillapaugh-Fay, Gwen; Urrutia, Enrique

doi:10.1148/radiology.162.2.3797675

Cited by 33 publications

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“…Thus, the generation of a mAb that can distinguish fibrin clots from fibrinogen, soluble fibrin, and D-dimer represents a major breakthrough because these proteins share common amino acid sequences. The specificity of the 102–10 mAb differed from existing anti-fibrin mAbs (NYB-T2G12223 and MH-120), as the 102–10 mAb reacted only with fibrin clots (Supplementary Fig. 1b).…”

Section: Resultsmentioning

confidence: 92%

Discovery of an uncovered region in fibrin clots and its clinical significance

Hisada

Yasunaga

Hanaoka³

et al. 2013

Sci Rep

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Despite the pathological importance of fibrin clot formation, little is known about the structure of these clots because X-ray and nuclear magnetic resonance (NMR) analyses are not applicable to insoluble proteins. In contrast to previously reported anti-fibrin monoclonal antibodies (mAbs), our anti-fibrin clot mAb (clone 102–10) recognises an uncovered region that is exposed only when a fibrin clot forms. The epitope of the 102–10 mAb was mapped to a hydrophobic region on the Bβ chain that interacted closely with a counterpart region on the γ chain in a soluble state. New anti-Bβ and anti-γ mAbs specific to peptides lining the discovered region appeared to bind exclusively to fibrin clots. Furthermore, the radiolabelled 102–10 mAb selectively accumulated in mouse spontaneous tumours, and immunohistochemistry using this mAb revealed greater fibrin deposition in World Health Organization (WHO) grade 4 glioma than in lower-grade gliomas. Because erosive tumours are apt to cause micro-haemorrhages, even early asymptomatic tumours detected with a radiolabelled 102-10 mAb may be aggressively malignant.

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Section: Resultsmentioning

confidence: 92%

Discovery of an uncovered region in fibrin clots and its clinical significance

Hisada

Yasunaga

Hanaoka³

et al. 2013

Sci Rep

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“…The critical question is how much aging? Radioimmunoimaging with a fibrin-specific monoclonal antibody showed that the concentration in fresh and up to 5 day-old thrombi were comparable 36. Molecular MR imaging of fibrin provides more detailed information on this; signal enhancement occurs in fresh thrombus and declines as the age of thrombus past 4 weeks 37.…”

Section: Discussionmentioning

confidence: 96%

Molecular MRI of Intracranial Thrombus in a Rat Ischemic Stroke Model

Uppal

Dai

et al. 2010

Stroke

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Background and Purpose-Intracranial thrombus is a principal feature in most ischemic stroke, and thrombus location and size may correlate with outcome and response to thrombolytic therapy. EP-2104R is a fibrin-specific molecular MR agent that has previously been shown to enhance extracranial and venous sinus thrombi in animal models and, recently, in clinical trials. In this study, we examined whether this fibrin-specific MR probe could noninvasively characterize intracranial arterial thrombi. Methods-Embolic stroke was induced in adult rats by occlusion of the right internal carotid artery with an aged thrombus.We used diffusion-weighted imaging, time of flight angiography, and high-resolution 3-dimensional T1-weighted MRI at 4.7 T before and after use of contrast agents EP-2104R (nϭ6) and gadopentetate dimeglumine (nϭ5). Results-In all animals, MR angiography revealed a flow deficit and diffusion-weighted imaging showed hyperintensity consistent with ischemia. Using EP-2104R-enhanced MRI, we saw occlusive thrombi and vessel wall enhancement in all 6 animals with high contrast to noise relative to blood, whereas gadopentetate dimeglumine-injected animals showed no occlusive thrombus or vessel wall enhancement. The concentration of gadolinium in the thrombus after EP-2104R was 18 times that in the blood pool. Conclusions-EP-2104R-enhanced MRI successfully identifies intracranial thrombus in a rat embolic stroke model. (Stroke.

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“…Therefore, the production of a monoclonal antibody that can distinguish a fibrin clot from fibrinogen, soluble fibrin, and D-dimer would be a major breakthrough because all of these substances have common amino acid sequences. The specificity of 102-10 IgG differs from existing anti-fibrin antibodies (i.e., NYB-T2G1 21 22 and MH-1 23 ), and as a result of its unique properties, it is not neutralized by fibrinogen, soluble fibrin, or D-dimer in the bloodstream. The amino acid sequence of the epitope of 102-10 IgG is completely conserved in mammals, birds, amphibians, and fish (Basic Local Alignment Tool, BLAST).…”

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confidence: 92%

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

Obonai

Fuchigami

Furuya

et al. 2016

Sci Rep

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The diagnosis of early and aggressive types of cancer is important for providing effective cancer therapy. Cancer-induced fibrin clots exist only within lesions. Previously, we developed a monoclonal antibody (clone 102-10) that recognizes insoluble fibrin but not fibrinogen or soluble fibrin and confirmed that fibrin clots form continuously in various cancers. Here, we describe the development of a Fab fragment probe of clone 102-10 for tumour imaging. The distribution of 102-10 Fab was investigated in genetically engineered mice bearing pancreatic ductal adenocarcinoma (PDAC), and its effect on blood coagulation was examined. Immunohistochemical and ex vivo imaging revealed that 102-10 Fab was distributed selectively in fibrin clots in PDAC tumours 3 h after injection and that it disappeared from the body after 24 h. 102-10 Fab had no influence on blood coagulation or fibrinolysis. Tumour imaging using anti-fibrin Fab may provide a safe and effective method for the diagnosis of invasive cancers by detecting fibrin clots in tumour stroma.

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Aged venous thrombi: radioimmunoimaging with fibrin-specific monoclonal antibody.

Cited by 33 publications

References 0 publications

Discovery of an uncovered region in fibrin clots and its clinical significance

Discovery of an uncovered region in fibrin clots and its clinical significance

Molecular MRI of Intracranial Thrombus in a Rat Ischemic Stroke Model

Tumour imaging by the detection of fibrin clots in tumour stroma using an anti-fibrin Fab fragment

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