SBIR-STTR Award

The investigators propose to test the feasibility of developing a method for nuclear medical imaging of thromboembolism with a technetium-99m-labeled CSVTCG peptide fragment of thrombospondin protein, both of which bind to the major platelet glycoprotein, CD36, as further described by their abstract: "With nearly half a million incidences and 200,000 deaths due to deep venous thrombosis (DVT) and pulmonary embolism (PE) in the USA each year, and their enigmatic, non-invasive diagnostic assessment, the need for a Tc-99m agent that can detect DVT or PE promptly and reliably is more dire than ever before. While a large number of radiolabeled monoclonal antibodies, most of them specific for platelet surface glycoprotein IIb- IIIa complex have been investigated, for a variety of reasons none has yet made a significant contribution to the management of these patients. Unlike the three types of peptides, anti-platelet factor IV, DMP 444 and snake venom factors, being investigated as agents to detect PE and DVT, the peptide in question CSVTCG, is the one that exists naturally in the molecular domain of the most endogenous protein, thrombospondin, which takes an active part in the formation of DVT via activated platelets. Also, unlike the other three peptides, CSVTCG binds to major platelets glycoprotein CD 36 (GPIV, GPV). "We have successfully labeled CSVTCG with Tc-99m, examined its biological activity and determined its ability to selectively bind to activated platelets via GP CD 36. We have evaluated Tc-99m-CSVTCG (Tc-99m-TP-1201) to label forming and preformed blood clots in vitro and to detect an experimental DVT in vivo. The results have been highly encouraging and have generated the impetus that has prompted us to undertake this systematic feasibility study that will determine its potential as an agent for scintigraphic imaging of DVT and PE."

Thesaurus Terms:
contrast media, imaging /visualization, peptide, technetium, thromboembolism, thrombospondin CD antigen, biotechnology, method development, peptide chemical synthesis, pulmonary circulation obstruction, venous thrombosis

Each year in the USA, more than 500,000 patients are hospitalized with venous thrombosis (VT) and pulmonary embolism (PE). Of these patients, nearly 200,000 die. Despite the magnificent advances in imaging techniques, diagnosis of VT and PE continues to be challenging. Because scintigraphic imaging technique is simple, non-invasive, and permits rapid scanning of the entire body, the FDA has recently approved Tc-99m-AcuTect for imaging clots. AcuTect, however, can neither image old clots nor detect most PE. Fibrin is a major, integral part of VT, fresh or old, as well as of PE. During our NIH Phase I study we have developed Tc-99m-fibrin specific peptide, with which in vitro and in vivo imaging results are promising. Our primary goals in the Phase II studies are to evaluate the ability of this agent (Tc-99m/ TP 850) i) to image up to 96 hr old VT and PE, ii) to compare the efficacy of Tc-99m-TP 850 with Tc 99m-AcuTect to image VT and PE, iii) to examine the efficacy of Tc-99m-TP 850 to image fresh and old VT and PE treated in vivo with anticoagulating agent heparin, and iv) to perform pharmacokinetics and radiation dosimetry studies in 10 healthy human volunteers. We believe that the results of these studies will allow us to determine the full potential of Tc-99m-TP 850 and permit us to rapidly initiate clinical trials. PROPOSED COMMERCIAL APPLICATIONS: Following the proposed evaluation in swine and Phase I studies in humans, the agent should be ready to be examined in patients with DVT and PE. Because there are no agents currently available than can scintigraphically provide "hot spot" images of old (24 hr or older) clots and PE, the commercial potential for this agent is very high.

Thesaurus Terms:
biomarker, cardiovascular disorder diagnosis, cardiovascular imaging /visualization, diagnosis design /evaluation, fibrin, nuclear medicine, peptide analog, radiotracer, technetium, thromboembolism anticoagulant, clinical trial, diagnosis procedure safety, pharmacokinetics, radiation dosage, thrombospondin, venous thrombosis autoradiography, bioimaging /biomedical imaging, biotechnology, human subject, laboratory mouse, laboratory rabbit, patient oriented research, peptide chemical synthesis, swine