Thrombus Imaging with Radiolabeled Peptides

Deep vein thrombosis (DVT) and resultant pulmonary emboli (PE) represent significant morbidity and mortality in the U. S. A. Existing detection modalities such as contrast venography, ultrasound, and non-specific radiopharmaceuticals do not exhibit the sensitivity or specificity in all areas of interest to reliably detect DVT or PE. A Tc-99m radiolabeled thrombus-binding peptide would be ideally suited to this task by virtue of its specificity, favorable pharmacokinetics, and low-cost isotope, and widely available nuclear medicine facilities. As platelets are a component of thrombi, synthetic peptides that bind with high affinity to the GPIIb/IIIa receptor on the surface of activated platelets provide a rational basis for the development of a thrombus-specific radiopharmaceutical. We now have preliminary in vitro and in vivo data that indicate that this is a viable approach. We propose to build on our initial work by synthesizing additional Tc-99m labelable peptides with improved thrombus-binding and pharmacokinetic characteristics. We also propose to evaluate them in vitro and in animal models of DVT and PE. The peptide(s) exhibiting optimal characteristics will be selected for biodistribution and toxicological studies in support of clinical trials for the diagnosis of DVT and PE.