Labeling of human clots in vitro with an active-site mutant of t-PA
- Washington Univ. School of Medicine, St. Louis, MO (USA)
Prompt detection of acute thrombosis and its response to treatment with thrombolytic agents generally require angiography. Scintigraphic approaches with labeled antibodies to or components of the coagulation and fibrinolytic systems have been disappointing because of prolonged circulating half-lives of tracers and relatively slow or limited binding to thrombi. Accordingly, we developed and characterized a thrombolytically inactive, active-site mutant (Ser-478----Thr) of tissue-type plasminogen activator (t-PA) designed to detect thrombi in vivo. Binding of iodine-125-({sup 125}I) labeled Ser----Thr t-PA to thrombi in vitro was time- and concentration-dependent, and specific judging from inhibition by pre-incubation with anti-t-PA IgG. Clearance of 125I-labeled mutant t-PA in rabbits was rapid and biexponential (alpha t1/2 = 1.9 +/- 0.4 min, beta t1/2 = 39.8 +/- 11.2 min). Thus, the amidolytically inactive mutant of t-PA designed binds rapidly and specifically to human thrombi in vitro and is cleared rapidly from the circulation in vivo--properties rendering it attractive as a potentially useful clot imaging agent.
- OSTI ID:
- 7137429
- Journal Information:
- Journal of Nuclear Medicine; (USA), Vol. 31:2; ISSN 0161-5505
- Country of Publication:
- United States
- Language:
- English
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RADIOPHARMACEUTICALS
METABOLISM
THROMBOSIS
DIAGNOSIS
CLEARANCE
DOSE-RESPONSE RELATIONSHIPS
IN VITRO
IODINE 125
MAN
PLASMINOGEN
SERINE
TIME DEPENDENCE
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
CARBOXYLIC ACIDS
CARDIOVASCULAR DISEASES
DAYS LIVING RADIOISOTOPES
DISEASES
DRUGS
ELECTRON CAPTURE RADIOISOTOPES
FIBRINOLYTIC AGENTS
HEMATOLOGIC AGENTS
HYDROXY ACIDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
LABELLED COMPOUNDS
MAMMALS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
PRIMATES
RADIOISOTOPES
VASCULAR DISEASES
VERTEBRATES
550601* - Medicine- Unsealed Radionuclides in Diagnostics