Preliminary CommunicationsLOCALISATION OF DEEP-VENOUS THROMBOSIS USING TECHNETIUM-99m-LABELLED UROKINASE
Abstract
99mTc (technetium)-labelled urokinase has been used to detect and localise venous thrombosis in the lower limbs. In twenty-two patients the results correlated well with those of venography. It is suggested that this method will detect both formed and forming thrombi, in contrast to the 125I-labelled fibrinogen method which will only efficiently detect actively forming thrombi. Radioisotope scanning with 99mTc-labelled urokinase can be completed within 1 hour of injection and gives good visualisation of the calf, femoral, and ileofemoral segments.
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Cited by (23)
In vivo behaviour of vesicular urokinase
2005, International Journal of PharmaceuticsThromboembolic diseases including deep vein thrombus (DVT) are major causes of morbidity and mortality. Detection of DVT in low extremities is difficult. There are some accepted imaging techniques in clinic but most of them have several disadvantages limiting their effective use. Because of this, researchers are still performed to develop a rapid, specific means of detecting and/or imaging venous thrombi-based on the changing composition of the thrombus.
Urokinase, fibrinolytic enzyme isolated form human urine, is a direct activator of plasminogen. In thrombus formation, plasminogen seems to be trapped in or absorbed onto fibrin matrix thus leading to a localised concentration of plasminogen. This suggests that radiolabelled urokinase would be a suitable compound for the detection of thrombi. The most important disadvantage of this enzyme is short plasma half life. To overcome this problem, it was decided to encapsulate the enzyme in drug delivery systems such as liposomes, niosomes or sphingosomes.
In this study, we prepared, characterized and monitored the biodistribution of three types of vesicular systems containing urokinase. All types of prepared vesicles show in vitro an acceptable encapsulation, stability and release profile. Thrombus uptake was increased by encapsulation of urokinase into vesicles.
Diagnostic management of venous thromboembolism
1998, Bailliere's Clinical HaematologyThe accuracy of diagnostic methods for the diagnosis of deep vein thrombosis and pulmonary embolism in symptomatic patients is critically reviewed. In addition, the safety of withholding anticoagulant therapy from patients with suspected deep vein thrombosis or pulmonary embolism in whom the qualified diagnostic strategy was normal is evaluated by determining the frequency of venous thromboembolic complications during 3 months of follow-up. It is shown that the currently used available diagnostic techniques for deep vein thrombosis are all able to identify the majority of patients who indeed have venous thrombosis. However, as result of its accuracy and practical advantages, compression ultrasound is the test of choice in the evaluation of symptomatic patients. Patients with a normal test outcome should be re-tested to detect the small proportion of patients with proximally extending calf vein thrombosis. In the strategy of repeated diagnostic testing, impedance plethysmography could be used as an alternative to ultrasonography. To obtain a reduction in repeat tests various diagnostic strategies have been evaluated and it was shown that these strategies, using non-invasive tests, can be as accurate and safe as the invasive reference strategy. The safeties of the various strategies were very similar; however, important differences were observed with respect to the practical implementation of the various diagnostic strategies. Simplification of the repeated testing strategy by using a D-dimer assay and/or a clinical decision rule seems to be promising. The reference standard for the diagnosis of pulmonary embolism remains pulmonary angiography. Several strategies based on non-invasive diagnostic methods have been evaluated for their safety and complexability. Perfusion-ventilation lung scanning is the most thoroughly evaluated non-invasive technique so far. It seems safe to withhold anticoagulant therapy in patients suspected of pulmonary embolism with a normal perfusion lung scan result; however, further testing is needed in the case of a non-diagnostic perfusion-ventilation lung scan result. At this moment angiography is the method of choice in this category of patients. D-dimer assays, clinical decision rules and ultrasound examinations of the legs seem to have a high potential to limit the need for angiography. Also, spiral computerized tomography and magnetic resonance imaging are promising techniques, but their role in the diagnostic management of pulmonary embolism is still uncertain.
Salivary beta-thromboglobulin: A possible marker for deep vein thrombosis following elective hip surgery
1986, Thrombosis ResearchThe concentration of the platelet specific protein B-thromboglobulin, (BTG) was measured in salivary samples obtained pre and postoperatively from 30 patients without evidence of renal disease and having total hip replacement arthroplasty. When postoperative deep-vein thrombosis (DVT) was detected using percutaneous ascending phlebography there was total correlation with elevated salivary BTG levels taking 0.33 Wg/1 or greater on 2 consecutive occasions or more as indicating a deep venous thrombus. Eight of nine patients with a positive diagnosis of DVT on urokinase scanning would have been diagnosed using the same criterion. However BTG was elevated in a further 5 patients in whom labelled urokinase failed to demonstrate a DVT. These may have been localised in the calf and thus missed by, or lysed prior to, the scanning technique.
Clinical features and diagnosis of venous thrombosis
1986, Journal of the American College of CardiologyThe clinical diagnosis of venous thrombosis is inaccurate because the clinical findings are both insensitive and nonspecific. The sensitivity of clinical diagnosis is low because many potentially dangerous venous thrombi are clinically silent. The specificity of clinical diagnosis is low because the symptoms or signs of venous thrombosis all can be caused by nonthrombotic disorders. For these reasons, a practical approach for the diagnosis of venous thrombosis is important. A current approach to the diagnosis of clinically suspected venous thrombosis favors the use of impedance plethysmography over Doppler ultrasonography as the main test for this disorder. This is because impedance plethysmography is precise and objective, whereas the interpretation of Doppler ultrasonography is subjective and requires considerable skill and experience to form reliable diagnoses.
The use of serial impedance plethysmography has been evaluated recently in a prospective study. The rationale of repeated impedance plethysmography evaluation is based on the premise that calf vein thrombi are only clinically important when they extend into the proximal veins, at which point detection with impedance plethysmography is possible. Therefore, by performing repeated examinations with impedance plethysmography in patients with clinically suspected venous thrombosis, it is possible to identify patients with extending calf vein thrombosis who can be treated appropriately. Impedance plethysmography is performed immediately on referral; if it is positive in the absence of clinical conditions that are known to produce falsely positive results, the diagnosis of venous thrombosis is established, and the patient is treated accordingly. If the result of the initial impedance plethysmography evaluation is negative, anticoagulant therapy is withheld, and impedance plethysmography is repeated the following day, again on day 5 to 7 and on day 10 to 14. If impedance plethysmography becomes positive during this time, a diagnosis of venous thrombosis is made and anticoagulant therapy is commenced.
Positive impedance plethysmography in the presence of conditions known to produce a false positive result (for example, congestive cardiac failure) should be confirmed by venography. If noninvasive tests for the diagnosis of venous thrombosis are not available, a clinical suspicion of venous thrombosis should be objectively confirmed or excluded by performing ascending venography.
Radiopharmaceuticals for thrombus detection: Selection, preparation, and critical evaluation
1977, Seminars in Nuclear MedicineNearly a decade has passed since the introduction of 125I-fibrinogen as a tracer to aid in the clinical diagnosis of thrombosis. During this time many new radiopharmaceuticals have been developed for the detection of thrombi. Most of these have been designed to overcome the primary disadvantages of 125I-fibrinogen for uptake tests, namely, that it is limited to evaluation of the extremities, and it does not provide a scintigraphic image. Iodine-125-fibrinogen is now commercially available in the United States. We, therefore, concentrated our review on agents labeled with short-lived gamma-emitting nuclides useful for scintigraphy: 123I, 111In, 77Br, and 99mTc. In addition to being tagged with a variety of short-lived isotopes, fibrinogen has been chemically modified by overiodination and by clot formation/dissolution in attempts to accelerate its biologic clearance. These modifications have resulted in higher thrombus: blood ratios measured at earlier times when the photon flux is still high. Labeled leukocytes and platelets also have been tested as thrombus-localizing agents, and several components of the fibrinolytic system, including plasminogen, streptokinase, and urokinase, have been purified and labeled with iodine and/or technetium. The later agents could prove particularly useful for localizing older thrombi in which net fibrin deposition has slowed. Among the radiopharmaceuticals described for thrombus scintigraphy, chemically modified and fast clearing 123I-fibrinogen, 111In-platelets, and 123I-plasminogen show the greatest potential and should find extensive clinical application in the immediate future.
Radiopharmaceuticals labelled with Technetium
1977, The International Journal Of Applied Radiation And IsotopesThe ready availability and ideal nuclear properties of 99mTc has led to its widespread use for imaging purposes. In general the localization of the present radiopharmaceuticals is based on the ability of an organ to remove foreign substances from the blood. Further application of this ideal nuclide seems related to the development of methods to label biologically active molecules or drugs in such a way as not to interfere with their desired in vivo behaviour. However, directly binding the 99mTc to these molecules may prevent the expected distribution (except in the case of large molecular weight proteins and cells) by altering the critical functional groups. Therefore the synthesis of derivatives containing a chelating group to bind the technetium is suggested as a possible solution to the problems associated with direct labelling. This could result in a molecule with similar biological properties to the parent molecule. But before useful derivatives of biologically active molecules and drugs can be prepared, extensive study of the chemistry of 99mTc is needed.