{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T22:24:01Z","timestamp":1768515841624,"version":"3.49.0"},"reference-count":0,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1990,11]]},"abstract":"<jats:p>Chemical conjugates between recombinant single-chain urokinase-type plasminogen activator (rscu-PA) and a murine monoclonal antibody directed against fragment D-dimer of cross-linked human fibrin (MA-15C5), rscu-PA\/MA-15C5, and between rscu-PA and a control monoclonal antibody (MA-1C8), rscu-PA\/MA-1C8, were produced by cross-linking with N-succinimidyl 3-(2-pyridyldithio) propionate (SPDP). In an in vitro system composed of a [125 I]fibrin-labeled baboon plasma clot immersed in autologous citrated plasma, dose- and time-dependent lysis was obtained with a ratio of the potencies of free and conjugated rscu-PA similar to that in human plasma: 50% lysis in 2 hours required 4.3 micrograms\/ml rscu-PA, 1.0 microgram\/ml urokinase-type plasminogen activator (u-PA) equivalent rscu-PA\/MA-15C5, or 15 micrograms\/ml u-PA equivalent rscu-PA\/MA-1C8. The thrombolytic and pharmacokinetic properties of rscu-PA and of rscu-PA\/MA-15C5 were compared in baboons with a 0.8-1.0 ml [125 I]fibrin-labeled autologous blood clot produced in a femoral vein. Continuous intravenous infusion of these compounds during a 2-hour period resulted in dose- and time-dependent lysis. The thrombolytic potency of rscu-PA\/MA-15C5 was 3.0 +\/- 0.5 times higher (50% lysis with 0.3 +\/- 0.02 mg u-PA equivalent\/kg body wt) than that of rscu-PA measured by ex vivo isotope recovery from the femoral vein segment (p less than 0.001) and was 2.7 +\/- 0.5 times higher (50% lysis with 0.35 +\/- 0.02 mg\/kg rscu-PA\/MA-15C5) by external radioisotope counting (p less than 0.001). A dose of 0.5 mg\/kg of rscu-PA\/MA-1C8 was much less active than rscu-PA. After the end of the infusion, u-PA-related antigen disappeared from plasma in a biphasic manner with an initial half-time of 2.7 +\/- 0.5 for rscu-PA, 24 +\/- 1.2 for rscu-PA\/MA-15C5, and 21 +\/- 0.5 minutes for rscu-PA\/MA-1C8 with corresponding plasma clearances of 340 +\/- 40, 20 +\/- 3, and 24 +\/- 2 ml\/min, respectively. In conclusion, the increased thrombolytic potency of rscu-PA\/MA-15C5 is the result of a reduction of the thrombolytic potency due to coupling of rscu-PA to the antibody molecule, which is counter-balanced by an enhancement of the thrombolytic potency due to fibrin targeting by the specific idiotype.<\/jats:p>","DOI":"10.1161\/01.cir.82.5.1744","type":"journal-article","created":{"date-parts":[[2011,6,17]],"date-time":"2011-06-17T20:29:13Z","timestamp":1308342553000},"page":"1744-1753","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":25,"title":["Thrombolytic and pharmacokinetic properties of a conjugate of recombinant single-chain urokinase-type plasminogen activator with a monoclonal antibody specific for cross-linked fibrin in a baboon venous thrombosis model."],"prefix":"10.1161","volume":"82","author":[{"given":"D","family":"Collen","sequence":"first","affiliation":[{"name":"Center for Thrombosis and Vascular Research, University of Leuven, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M","family":"Dewerchin","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Vascular Research, University of Leuven, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H J","family":"Rapold","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Vascular Research, University of Leuven, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H R","family":"Lijnen","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Vascular Research, University of Leuven, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J M","family":"Stassen","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Vascular Research, University of Leuven, Belgium."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","container-title":["Circulation"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/pdf\/10.1161\/01.CIR.82.5.1744","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T16:05:08Z","timestamp":1715529908000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.CIR.82.5.1744"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1990,11]]},"references-count":0,"journal-issue":{"issue":"5","published-print":{"date-parts":[[1990,11]]}},"alternative-id":["10.1161\/01.CIR.82.5.1744"],"URL":"https:\/\/doi.org\/10.1161\/01.cir.82.5.1744","relation":{},"ISSN":["0009-7322","1524-4539"],"issn-type":[{"value":"0009-7322","type":"print"},{"value":"1524-4539","type":"electronic"}],"subject":[],"published":{"date-parts":[[1990,11]]},"assertion":[{"value":"1990-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}