Radiopharmaceuticals for thrombus detection

Knight, Linda C.

doi:10.1016/s0001-2998(05)80176-x

Cited by 23 publications

(17 citation statements)

References 88 publications

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“…Radiopharmaceuticals which have previously been tested for imaging of deep vein thrombosis (DVT) have suffered from various limitations (21). For example, radiolabeled platelets and fibrinogen exhibited very slow blood clearance and poor binding to mature thrombi, which precluded their ability to image pre-existing thrombi in a rapid manner.…”

Section: Discussionmentioning

confidence: 99%

Platelet binding and biodistribution of [99mTc]rBitistatin in animal species and humans

Knight

Romano

Bright

et al. 2007

Nuclear Medicine and Biology

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INTRODUCTION-99m Tc-rBitistatin is a radioligand for the αIIbβ3 (GPIIb/IIIa) receptor on platelets and is being developed as a diagnostic radiopharmaceutical for in vivo imaging of acute thrombi and emboli. Prior to the first administration of 99m Tc-rBitistatin to human subjects, its biodistribution and effects on platelets were evaluated in animals. This paper reports the findings of the animal studies in comparison with the initial findings in normal human subjects.

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Section: Discussionmentioning

confidence: 99%

Platelet binding and biodistribution of [99mTc]rBitistatin in animal species and humans

Knight

Romano

Bright

et al. 2007

Nuclear Medicine and Biology

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“…Recombinant t-PA is used in fibrinolytic treatment of acute myocardial infarction. However, inactivation of the radiolabelled recombinant t-PA by rapid hepatic clearance and plasminogen activator inhibitors in plasma make this approach unfit for in vivo application (Knight 1990).…”

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confidence: 99%

Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

et al. 1991

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The administration of a radiolabelled monoclonal antibody against tissue plasminogen activator allows detection of areas with increased fibrinolytic activity, i.e. those with an active thrombotic lesion. Eight patients with phlebographically verified deep venous thrombosis were examined. At the time of immunoscintigraphy study they were examined receiving anticoagulant therapy. Some 75-85 MBq indium 111-labelled antibody were injected, and scintigrams were obtained after 30 min and after 24 h. The precise site of the thrombus could not be visualized after 30 min due to high background activity, whereas after 24 h it was detectable in all patients. The thrombus/background ratios achieved are twice as high as those observed in a human antifibrin antibody study. These preliminary data suggest a high sensitivity of our t-PA-specific antibody for the detection of active deep venous thrombosis in man, and our antibody seems to offer theoretical advantages over both platelet and fibrin-specific antibodies.

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“…20 Therefore, it is postulated that an overwhelming dose of extrinsic t-PA is required for positive delineation of the clot. 3 Another point is the short retention of intravenously administered t-PA after binding to fibrin clots. 21,22 Preliminary imaging studies suggest that Tc-99m t-PA accumulated immediately at the clot site, but the period of its positive delineation did not seem to exceed for only 10 to 15 minutes.…”

Section: Discussionmentioning

confidence: 99%

“…Various radiopharmaceuticals have been developed for defining vascular thrombi. 2,3 Anti-platelet antibodies4 '5 and anti-fibrin antibodies 6 have recently been shown to accumulate specifically in both fresh and old thrombi. However, radiolabeled antibodies have some limitations for routine clinical use becuase of their slow blood clearance and non-human protein origin.…”

Section: Introductionmentioning

confidence: 99%

Tc-99m labeled tissue-type plasminogen activator: Preparation, stability and preliminary imaging of thrombus-bearing rats

et al. 1991

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Tissue-type plasminogen activator (t-PA) is a thrombolytic agent that directly binds to fibrin formed in clots. In terms of radiolabeling and nuclear imaging, t-PA has several advantages in Tc-99m labeling: it is stable in acidic solution at pH 3, which is suitable for labeling Tc-99m by a method of stannous reduction and blood disappearance after administration is rapid, which is desirable for imaging targets using short-lived radionuclides. Recombinant t-PA was labeled with Tc-99m by a method of stannous reduction without significant degradation of biochemical activity, over 95% of which was retained after the labeling procedure. Labeling efficiency in paper chromatography was over 98%. The moiety of hydrolyzed Tc-99m that was not eluted through the Sephadex column was estimated to be less than 10%. Tc-99m labeled t-PA, however, appeared to become unstable when diluted with normal saline. Nevertheless, in in vitro fibrin binding, Tc-99m labeled t-PA showed high affinity with fibrin: 80% of 100 ng/ml of Tc-99m t-PA bound to 10(-5) mol of the fibrinogen. Preliminary animal studies also showed a concentration of Tc-99m labeled t-PA at fresh thrombi formed in the inferior vena cava. Tc-99m labeled t-PA appears to have potential for thrombus imaging and the preparation of an instant kit.

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Radiopharmaceuticals for thrombus detection

Cited by 23 publications

References 88 publications

Platelet binding and biodistribution of [99mTc]rBitistatin in animal species and humans

Platelet binding and biodistribution of [99mTc]rBitistatin in animal species and humans

Detection of deep venous thrombosis with indium 111-labelled monoclonal antibody against tissue plasminogen activator

Tc-99m labeled tissue-type plasminogen activator: Preparation, stability and preliminary imaging of thrombus-bearing rats

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