Bacterial infections such as those of prosthetic joints, bones (osteomyelitis) and heart valves (infective endocarditis) are difficult to diagnose and treat, and are a major cause of mortality, morbidity and health care costs. The long-term goal of our program is to develop a positron emission tomography (PET) radiotracer that can be used for non-invasive PET imaging to detect and localize bacterial pathogens in humans. This radiotracer will serve as a non-invasive diagnostic to accurately identify bacterial infections and inform on bacterial load during chemotherapy, thereby identifying and improving treatment outcomes of patients with infectious diseases. We have synthesized a novel radiotracer, CC-001, that is selectively taken up by bacteria including clinically relevant strains of Staphylococcus aureus. We have shown that CC-001 accumulates at the site of S. aureus infection in a soft tissue infection model of disease. Significantly, CC-001 can distinguish bacterial infection from inflammation unlike the widely used clinical PET tracer 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG). The object of this Phase I STTR is to validate CC-001 in a preclinical model of infection and perform studies in preparation for an investigational new drug submission.
In Aim 1 we will demonstrate that CC-001 can detect and image S. aureus in a preclinical model of infective endocarditis and that this radiotracer can quantify bacterial load as a function of antibiotic treatment.
In Aim 2 we will perform dosimetry studies in order to assess the projected radiation exposure at a clinically relevant human dose. We will also demonstrate that CC-001 does not display any adverse effects at 100 and 1000 times the projected human dose in mice. Thus, we will show that radiation burden and toxicity resulting from the dose of radiotracer proposed for clinical studies is within the acceptable range based on data from the U.S Food and Drug Administration. This Phase I STTR will pave the way for a Phase II STTR in which we will gather additional preclinical data and subsequently transition into clinical trials.
Many human bacterial infections including those of the heart, are difficult to detect and treat due to their location in the human body and are a serious cause of morbidity and health care costs. To meet this unmet medical need, we will validate a radiotracer that can detect and localize bacterial pathogens in humans using positron emission tomography imaging. This radiotracer can serve as a non-invasive diagnostic and inform on bacterial load during chemotherapy, thereby identifying and improving treatment of patients with infectious diseases.
