title: Tc-99m labeled tissue-type plasminogen activator: preparation, stability and preliminary imaging of thrombus-bearing rats.
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, 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.
authors.affiliation: Department of Nuclaer Medicine, Hokkaido University School of Medicine, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Itoh
authors.forename: E
authors.initials: E
authors.lastname: Tsukamoto
authors.forename: T
authors.initials: T
authors.lastname: Nishibe
authors.forename: S
authors.initials: S
authors.lastname: Sakurama
authors.forename: M
authors.initials: M
authors.lastname: Ieko
authors.forename: T
authors.initials: T
authors.lastname: Tanabe
authors.forename: M
authors.initials: M
authors.lastname: Furudate
mesh_terms: D000818:Animals; D004355:Drug Stability; D015609:Organotechnetium Compounds; D011877:Radionuclide Imaging; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013927:Thrombosis / Q000000981:diagnostic imaging*; D010959:Tissue Plasminogen Activator
chemical_list: D015609:Organotechnetium Compounds; D011994:Recombinant Proteins; C072781:technetium Tc 99m-tissue-type plasminogen activator; D010959:Tissue Plasminogen Activator