The probe, called 18F-FAC, was created by slightly altering the molecular structure of gemcitabine, one of the most common chemotherapy drugs, and adding a radiolabel to enable PET visualization. Its action is based on the DNA salvage pathway - a fundamental biochemical pathway that helps with DNA replication and repair. All cells use this pathway, but in lymphocytes and macrophages (the cells that initiate immune response) the pathway is activated at high levels. Thus the probe accumulates to a far greater extent in such cells.
Conventional treatment-response monitoring, such as measuring the change in tumour size with MR and CT scans, for example, can take weeks or even months to determine a patient's response. This means that patients who don't respond are exposed to potentially toxic therapies for longer than necessary. If the new PET probe can monitor immune activity and treatment response in a much shorter time - say, within a week or two - patients could be spared from undergoing therapies that aren't working.
This type of dynamic probe should also enable cancer researchers to learn more about the role of immune response in fighting or, in some cases, stimulating tumour growth. Molecular imaging will shed light on how current cancer treatments affect immune cells and allow oncologists to quantitatively monitor responses to new modalities such as tumour vaccines. The new probes may also help identify tumours that will respond to certain drugs, thus enabling more patient-specific treatments.
According to the Jonsson Cancer Center researchers, this work was prompted by the desire to develop PET probes that monitor different molecular functions to existing probes. "We wanted to develop new ways to look inside a living organism and gather as much information as we can about the immune system," explained Caius Radu. "We wanted to know how cells move from one site in the body to another and find a way to trace them to tumours. This probe will tell us things about the immune system that existing probes can't."
The team evaluated 18F-FAC-PET in mouse models of anti-tumour immunity. The probe was sensitive to localized immune activation and enabled visualization of the thymus and spleen, with better selectivity for these lymphoid organs than 18F-FDG and 18F-FLT probes. 18F-FAC microPET also detected early changes in lymphoid mass in systemic autoimmunity and allowed evaluation of immunosuppressive therapy.
Potential disadvantages of 18F-FAC include its baseline retention in lymphoid organs, which could hamper the detection of weak immune responses at these sites, and its relatively high retention in the small and large intestines. The researchers plan to evaluate the probe further in subsequent studies and eventually hope to monitor the immune systems of patients with 18F-FAC and other PET probes.
"This is not a cure or a new treatment, but it will help us to more effectively model and measure the immune system," explained researcher Owen Witte. "This measurement is not invasive - it involves a simple injection of the probe. We could do repetitive scans in a single week to monitor immune response."