Abstract
Fragment E1, a product of plasmic digestion of cross-linked fibrin, binds specifically in vitro to polymerized fibrin but not to fibrinogen. Purified human Fragment E1 was radiolabeled with 125I or 131I by the Iodogen technique. The uptake of radioiodinated Fragment E1 in vitro into forming or preformed clots was demonstrated. Animal biodistribution studies of radioiodinated Fragment E1 showed its rapid removal from the circulation; radioactive catabolites did not reside long in any organ and were excreted in the urine. The uptake in vivo was evaluated in pigs with preexisting venous thrombi of various ages from 1 h up to 5 d at the time of intravenous systemic injection of the tracer. Radioiodinated fibrinogen was also injected into the same animals to compare the uptake of the two tracers. Thrombus-to-blood ratios for Fragment E1 averaged 43:1 (range 10-108) and 29:1 (range 8-107) in thrombi 1-6 h and 1-5 d old, respectively. In contrast, mean thrombus-to-blood ratios for fibrinogen were, in the same time intervals, 26:1 (range 17-41) and 2:1 (range 0.5-3.9), respectively. It is concluded that radioiodinated Fragment E1 is a specific marker of thrombi in vivo: its uptake by fresh thrombi is better than that of labeled fibrinogen and, in contrast to radioiodinated fibrinogen, this fragment is incorporated into old thrombi as well.
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Selected References
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- Coleman R. E., Harwig S. S., Harwig J. F., Siegel B. A., Welch M. J. Fibrinogen uptake by thrombi: effect of thrombus age. J Nucl Med. 1975 May;16(5):370–373. [PubMed] [Google Scholar]
- DAVIS B. J. DISC ELECTROPHORESIS. II. METHOD AND APPLICATION TO HUMAN SERUM PROTEINS. Ann N Y Acad Sci. 1964 Dec 28;121:404–427. doi: 10.1111/j.1749-6632.1964.tb14213.x. [DOI] [PubMed] [Google Scholar]
- Davis H. H., Heaton W. A., Siegel B. A., Mathias C. J., Joist J. H., Sherman L. A., Welch M. J. Scintigraphic detection of atherosclerotic lesions and venous thrombi in man by indium-111-labelled autologous platelets. Lancet. 1978 Jun 3;1(8075):1185–1187. doi: 10.1016/s0140-6736(78)90972-8. [DOI] [PubMed] [Google Scholar]
- Didisheim P. Animal models useful in the study of thrombosis and antithrombotic agents. Prog Hemost Thromb. 1972;1:165–197. [PubMed] [Google Scholar]
- Ezekowitz M. D., Wilson D. A., Smith E. O., Burow R. D., Harrison L. H., Jr, Parker D. E., Elkins R. C., Peyton M., Taylor F. B. Comparison of Indium-111 platelet scintigraphy and two-dimensional echocardiography in the diagnosis of left ventricular thrombi. N Engl J Med. 1982 Jun 24;306(25):1509–1513. doi: 10.1056/NEJM198206243062502. [DOI] [PubMed] [Google Scholar]
- Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
- Goodwin D. A., Bushberg J. T., Doherty P. W., Lipton M. J., Conley F. K., Diamanti C. I., Meares C. F. Indium-111-labeled autologous platelets for location of vascular thrombi in humans. J Nucl Med. 1978 Jun;19(6):626–634. [PubMed] [Google Scholar]
- Henkin R. E., Yao J. S., Quinn J. L., 3rd, Bergan J. J. Radionuclide venography (RNV) in lower extremity venous disease. J Nucl Med. 1974 Mar;15(3):171–175. [PubMed] [Google Scholar]
- KAZAL L. A., AMSEL S., MILLER O. P., TOCANTINS L. M. THE PREPARATION AND SOME PROPERTIES OF FIBRINOGEN PRECIPITATED FROM HUMAN PLASMA BY GLYCINE. Proc Soc Exp Biol Med. 1963 Aug-Sep;113:989–994. doi: 10.3181/00379727-113-28553. [DOI] [PubMed] [Google Scholar]
- Kakkar V. V., Nicolaides A. N., Renney J. T., Friend J. R., Clarke M. B. 125-I-labelled fibrinogen test adapted for routine screening for deep-vein thrombosis. Lancet. 1970 Mar 14;1(7646):540–542. doi: 10.1016/s0140-6736(70)90769-5. [DOI] [PubMed] [Google Scholar]
- Kakkar V. The diagnosis of deep vein thrombosis using the 125 I fibrinogen test. Arch Surg. 1972 Feb;104(2):152–159. doi: 10.1001/archsurg.1972.04180020032006. [DOI] [PubMed] [Google Scholar]
- Knight L. C., Budzynski A. Z., Olexa S. A. Radiolabeling of fibrinogen using the iodogen technique. Thromb Haemost. 1981 Oct;46(3):593–596. [PubMed] [Google Scholar]
- Knight L. C., Harwig S. L., Welch M. J. In vitro stability and in vivo clearance of fibrinogen or serum albumin labeled with 77Br, 131I, or 125I by direct or indirect synthetic methods. J Nucl Med. 1977 Mar;18(3):282–288. [PubMed] [Google Scholar]
- Knight L. C., Primeau J. L., Siegel B. A., Welch M. J. Comparison of In-111-labeled platelets and iodinated fibrinogen for the detection of deep vein thrombosis. J Nucl Med. 1978 Aug;19(8):891–894. [PubMed] [Google Scholar]
- McFarlane A. S. IN VIVO BEHAVIOR OF I-FIBRINOGEN. J Clin Invest. 1963 Mar;42(3):346–361. doi: 10.1172/JCI104721. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olexa S. A., Budzynski A. Z. Binding phenomena of isolated unique plasmic degradation products of human cross-linked fibrin. J Biol Chem. 1979 Jun 10;254(11):4925–4932. [PubMed] [Google Scholar]
- Olexa S. A., Budzynski A. Z., Doolittle R. F., Cottrell B. A., Greene T. C. Structure of fragment E species from human cross-linked fibrin. Biochemistry. 1981 Oct 13;20(21):6139–6145. doi: 10.1021/bi00524a035. [DOI] [PubMed] [Google Scholar]
- Olexa S. A., Budzynski A. Z. Evidence for four different polymerization sites involved in human fibrin formation. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1374–1378. doi: 10.1073/pnas.77.3.1374. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Olexa S. A., Budzynski A. Z. Primary soluble plasmic degradation product of human cross-linked fibrin. Isolation and stoichiometry of the (DD)E complex. Biochemistry. 1979 Mar 20;18(6):991–995. doi: 10.1021/bi00573a009. [DOI] [PubMed] [Google Scholar]
- Rosenthall L., Greyson N. D. Observations on the use of 99mTc albumin macroaggregates for detection of thrombophlebitis. Radiology. 1970 Feb;94(2):413–416. doi: 10.1148/94.2.413. [DOI] [PubMed] [Google Scholar]
- Sherry S. The problem of thromboembolic disease. Semin Nucl Med. 1977 Jul;7(3):205–211. doi: 10.1016/s0001-2998(77)80021-4. [DOI] [PubMed] [Google Scholar]
- Webber M. M., Bennett L. R., Cragin M., Webb R., Jr Thrombophlebitis--demonstration by scintiscanning. Radiology. 1969 Mar;92(3):620–623. doi: 10.1148/92.3.620. [DOI] [PubMed] [Google Scholar]
- York J. L., Blombäck B. The sites of the lactoperoxidase-catalyzed iodination of human fibrinogen. J Biol Chem. 1979 Sep 25;254(18):8786–8795. [PubMed] [Google Scholar]
