Radiolabeled peptides in the detection of deep venous thrombosis

Venous thrombosis and pulmonary embolism are major clinical problems that result in significant morbidity and mortality. It is estimated that 600,000 cases of pulmonary embolism occur each year in the United States, resulting in the death of approximately 100,000 patients. Most of these pulmonary emboli arise from deep venous thrombosis (DVT). The clinical diagnosis of DVT is unreliable. Only a third of patients with a clinical suspicion of DVT have objective evidence of the disease, and half of patients with proven DVT do not have any clinical symptoms. Although ascending contrast venography is the present standard for the diagnosis of DVT, duplex ultrasonography, which is increasingly used in combination with color Doppler flow imaging, is accepted as a useful clinical afternative to contrast venography. Both contrast venography and ultrasonography are imaging procedures that detect changes in venous anatomy that are caused by the presence of an intraluminal thrombus that is sufficiently formed either to reduce vascular filling with contrast medium or to resist compression. However, these imaging procedures do not reflect the metabolic activity of the clot, and therefore, they may overestimate the presence of active clots. The sensitivity of ultrasonography is also limited by various disease-related and technical factors. An alternative approach to the diagnosis of acute DVT is to detect a molecular marker of acute DVT that is not present in old, organized DVT. Recent advances in biotechnology permit the use of highly specific synthetic peptide or small molecular markers, which are involved in the acute stages of DVT formation and can be labeled efficiently with 99mTc. 99mTc-apcitide, a glycoprotein (GP IIb/IIIa) receptor antagonist previously known as 99mTc-P280, has been approved recently by the Food and Drug Administration for the clinical detection of acute DVT. Two other agents are currently under clinical investigation: 99mTc-DMP 444, which is another GP IIb/IIIa receptor antagonist, and 99mTc-Fibrin-Binding Domain (FBD), a radio-labeled fibrin-binding domain of fibronectin. Different clinical studies have shown a high diagnostic accuracy with these synthetic 99mTc-labeled peptides in the detection of acute DVT. Although further studies are needed to fully appreciate all of the diagnostic potential of these radiopharmaceuticals, the clinical introduction of 99mTcapcitide scintigraphy will certainly be helpful in expanding the use of nuclear medicine in a specific field in which it used to play a relatively marginal role.