Abstract
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, inin 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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Itoh, K., Tsukamoto, E., Nishibe, T. et al. Tc-99m labeled tissue-type plasminogen activator: Preparation, stability and preliminary imaging of thrombus-bearing rats. Ann Nucl Med 5, 59–64 (1991). https://doi.org/10.1007/BF03164615
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DOI: https://doi.org/10.1007/BF03164615