Abstract | OBJECTIVES: Either venous or arterial thrombosis is a potentially life-threatening event and existing diagnostic modalities are inadequate to diagnose and to determine the morphology of the evolving thrombus. Thus development of a noninvasive imaging agent that can detect clot location remains a critical and unmet need in nuclear diagnostic medicine. The present study was undertaken to determine the potential of platelet GPIIb/IIIa receptors compared with direct thrombin inhibitors, in the detection of venous and arterial clots. METHODS: Initially, the validity of exploiting the degree and extent of specific uptake and retention of a potent GPIIb/IIIa receptor antagonist in venous and in arterial thrombus was confirmed in vitro in artificially created arterial- or venous-type clots, using the radiolabeled antagonist, 3H-DMP728. This was followed by comparing the in-vivo clot/blood distribution of various technetium-99m (99mTc)-labeled, DMP728-derived, GPIIb/IIIa receptor antagonists and of thrombin inhibitors, over time, in mixed arterial/venous or venous clots in arteriovenous shunt and in venous clot models in dogs. In addition, we performed noninvasive single-photon emission tomographic imaging of the venous clot in a deep vein thrombosis model in dogs. RESULTS: Our data confirmed that potency for the platelet GPIIb/IIIa receptors was maintained after radiolabeling of the parent active GPIIb/IIIa receptor antagonists. DMP728 demonstrated a relatively greater affinity for activated than for unactivated human platelets, which might be essential for attaining an optimal thrombus/blood (target/background) distribution ratio and the optimal detection of small clots (i.e. greater sensitivity). CONCLUSIONS:
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Authors | S A Mousa, J M Bozarth, S Edwards, T Carroll, J Barrett |
Journal | Coronary artery disease
(Coron Artery Dis)
Vol. 9
Issue 2-3
Pg. 131-41
( 1998)
ISSN: 0954-6928 [Print] England |
PMID | 9647415
(Publication Type: Comparative Study, Journal Article)
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Chemical References |
- Mesylates
- Peptides, Cyclic
- Platelet Aggregation Inhibitors
- Platelet Glycoprotein GPIIb-IIIa Complex
- DMP 728
- Technetium
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Topics |
- Analysis of Variance
- Animals
- Diagnosis, Differential
- Disease Models, Animal
- Dogs
- Humans
- Mesylates
(metabolism)
- Peptides, Cyclic
(metabolism)
- Platelet Aggregation Inhibitors
(metabolism)
- Platelet Glycoprotein GPIIb-IIIa Complex
(metabolism)
- Radionuclide Imaging
- Sensitivity and Specificity
- Technetium
- Thrombophlebitis
(diagnostic imaging)
- Thrombosis
(diagnostic imaging)
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