To assess the potential use of the imaging agent in a disease setting, co-author Andrew Gelman, PhD, a professor of surgery, and colleagues modeled acute respiratory distress syndrome, a leading cause of intensive care death that can rapidly develop in patients with little to no warning. To do this, they injected mice with lipopolysaccharide, a molecule that stimulates reactive oxygen species production and is a component of many types of bacteria known to cause this disease.
PET scans revealed that the imaging agent was concentrated in the lungs of mice that had received lipopolysaccharide, and higher retention in lungs correlated with measurements of poor pulmonary function associated with this disease.
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"Visualizing reactive oxygen species generation should us allow us to better define patterns of tissue damage easily," Gelman said. "This tracer could help us assess changes in reactive oxygen species generation over the course of a disease progression, which would provide clinicians better information on when it's best to start and suspend therapy. Until now, we haven't had a tool to do that."
All PET tracers include a radioactive component that decays quickly, so the radioactive part must be made on site just before use. In general, this means that a hospital or research center that wants to do PET scanning needs to have access to a multimillion-dollar cyclotron to produce the radioactive components on demand. As a metal, however, gallium-68 can be produced with only a generator, which costs closer to $50,000, making it potentially affordable for sites with limited imaging budgets.
The researchers are now studying whether Galuminox can be used to study diseases characterized by chronic inflammation, such as lung transplant failure.
"Almost everyone who gets a lung transplant eventually ends up with transplant rejection, and we think it has to do with reactive oxygen species," Gelman said. "The typical lung transplant only lasts about five to six years. We think that a lot of the irreversible changes in the lungs occur before the patient has symptoms. By the time they start having difficulty breathing, it may be too late for effective treatment. If we could detect signs of inflammation early, we might be able to intervene at an earlier stage and extend the life span of the transplant. That's what we're looking at now."
Further development of Galuminox at MIR will be carried out in Sharma's laboratory in collaboration with Washington University's PET Radiotracer Translation and Resource Center, funded by the National Institute of Biomedical Imaging and Bioengineering. Led by Robert J. Gropler, MD, a professor of radiology and a co-author on this paper, the resource center aims to develop new PET tracers capable of delivering precision noninvasive imaging to improve diagnosis and understanding of a wide range of diseases.Back to HCB News