Research Project
2225090
Venous thromboembolism, comprising pulmonary embolism (PE) and deep vein thrombosis (DVT), and coronary, cerebral and carotid arterial thrombi represent substantial morbidity and mortality in the USA. Current methods of diagnosis of PE are either inaccurate (V/Q scans) or invasive (pulmonary angiography) and the localization of arterial thrombi requires either invasive angiography or indirect assessment. A rapid, noninvasive, accurate and cost-effective test which allows the direct visualization of PE, its source DVT and coronary, cerebral and carotid arterial thrombi is highly desirable. A Tc-99m radiolabeled thrombus-binding peptide is ideally suited to this task by virtue of its specificity, favorable pharmacokinetics, low-cost isotope and widely available nuclear medicine facilities. 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 pre-clinical and clinical data that indicate that this is a viable approach. Our pre-Phase I lead has given excellent results in imaging clinical DVT. Th Phase I, we identified compounds with even higher receptor-binding affinity and the ability to image lung thrombi in an animal model. In Phase II, we propose to investigate our lead compounds for their ability to directly visualize PE and arterial thrombi in humans. In addition, we propose to extend our QSAR study to identify a Tc-99m labeled GPIIb/IIIa receptor-binding peptide with optimized binding and pharmacokinetic characteristics. The product of this work will be a Tc- 99m labeled peptide imaging agent which will allow the imaging of PE, DVT, and arterial thrombi as a single test. PROPOSED COMMERCIAL APPLICATION: A Tc-99m labeled small, synthetic GPIIb/IIIa receptor-binding peptide capable of the noninvasive, accurate and cost-effective diagnosis of pulmonary embolism and arterial thrombi will have widespread use and substantial value.
