title: Rapid localization of indium-111-labeled inhibited recombinant tissue plasminogen activator in a rabbit thrombosis model.
abstract: The thrombus localizing properties of indium-111-recombinant tissue plasminogen activator (111In-rt-PA) have been investigated in an effort to achieve prompt and accurate detection of thrombi. Unlike previous studies with rt-PA, the active plasminogen catalytic site was permanently inhibited with peptides of chloromethyl ketone so that the radiotracer binds to fibrin without causing fibrinolysis. Thrombi were created in the external jugular vein of 14 male New Zealand white rabbits followed by injection of 111In-rt-PA. The agent cleared rapidly in vivo with a half-time of 4.6 min. The thrombus: blood ratio in nonheparinized rabbits (n = 7) was 6.39 +/- 0.86. The ratio in heparinized rabbits (n = 4) was 3.11 +/- 0.23. Thrombi were clearly visible in the planar images of both groups 1 hr postinjection. The combination of rapid thrombus localization and positive images, especially in the presence of anticoagulation, suggests that further work is warranted with rt-PA thrombus imaging.
authors.affiliation: Department of Radiology, Columbia-Presbyterian Medical Center, New York, New York 10032.
authors.forename: S P
authors.initials: SP
authors.lastname: Butler
authors.forename: K L
authors.initials: KL
authors.lastname: Kader
authors.forename: J
authors.initials: J
authors.lastname: Owen
authors.forename: T S
authors.initials: TS
authors.lastname: Wang
authors.forename: R A
authors.initials: RA
authors.lastname: Fawwaz
authors.forename: P O
authors.initials: PO
authors.lastname: Alderson
mesh_terms: D000590:Amino Acid Chloromethyl Ketones / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D003864:Depression, Chemical; D007205:Indium Radioisotopes; D007601:Jugular Veins; D008297:Male; D011817:Rabbits; D011877:Radionuclide Imaging; D011994:Recombinant Proteins; D013927:Thrombosis / Q000000981:diagnostic imaging / Q000378:metabolism*; D013997:Time Factors; D014018:Tissue Distribution; D010959:Tissue Plasminogen Activator / Q000493:pharmacokinetics*
chemical_list: D000590:Amino Acid Chloromethyl Ketones; D007205:Indium Radioisotopes; D011994:Recombinant Proteins; D010959:Tissue Plasminogen Activator; C040308:phenylalanyl-prolyl-arginine-chloromethyl ketone