A new radiotracer developed at the University of Alberta and soon to be tested in human clinical trials in Europe could make medical imaging of breast cancer tumours quicker and more accurate, and could one day lead to better treatments.
"Our work so far shows that it is far better for early detection and for detecting metastasis, so it could be a superior way to diagnose and stage breast cancer," says Frederick West, professor of chemistry and Allard Research Chair in Oncology, with appointments in the Faculty of Science and the Faculty of Medicine & Dentistry.
"It's going to make it much less inconvenient for patients to get these images, and we're going to get higher-quality images in the process, so from a patient outcome standpoint, the benefit is clear," says West.
West first began working on the new radiotracer in 2009, and was then joined in the work by Frank Wuest, professor and department chair of oncology and Dianne and Irving Kipnes Chair in Radiopharmaceutical Sciences, who did a comprehensive study of the radiotracer's behaviour with breast cancer models in mice in 2011.
The current standard molecule for cancer imaging using positron emission tomography is based on glucose. That's because cancer tumours grow so rapidly that they have a huge need for fuel, and as a result they have an unusual number of glucose transporter proteins to bring glucose into their cells. A radioactive isotope is added to the glucose-based tracer and when it is injected into the body, it is taken up more rapidly by the cancer cells than healthy cells. The tracer's positrons interact with the body's electrons, producing gamma rays that can then be detected by the PET scan.
The newly developed radiotracer, known as [18F]6-fluoro-6-deoxyfructose, mimics the structure of the natural sugar fructose instead, replacing a hydroxyl group with a radioactive fluorine isotope. It takes advantage of an unusual feature of breast cancer: A significant number of breast cancer cells take up fructose, thanks to a fructose transporter protein called GLUT5 that doesn't occur in normal breast tissue cells.
"The fructose transporter is actually very special because it's not found in very many of our cells," explains West.
When the fructose-based radiotracer is injected into the body, it is taken up by the GLUT5 in the cancer cells. The resulting gamma rays are then produced only in the cancer-affected locations, providing a very clear image.
"That's the perfect scenario," says West. "You want your image to light up like a bright light bulb and you want everything else in the background to be black. The problem with the glucose radiotracer is that every cell in our body uses glucose, so there's always going to be a background of gamma rays throughout the body because every cell is taking up the tracer molecule."
Another advantage of the fructose-based radiotracer is the time it takes to get an image. The glucose-based tracer takes up to two hours to accumulate in the tumour enough to be detected. In contrast, the fructose-based tracer lights up the tumour within 15 minutes, then is rapidly cleared from the body.
West and Wuest have so far tested their new radiotracer using animal models, but it will soon be tested in European patients.
"Our collaborators in Germany are motivated to test our compound in a small number of patients this year," says West. "If the results of these preliminary studies show promise, we would be able to fast-track clinical evaluation at the University of Alberta."
The next step, says West, is to consider whether the fructose transporter protein can be used in treatment as well as imaging.
"If we can selectively transport fructose into cancer cells and not into normal cells, the question we ask ourselves is, can we hijack that fructose transporter machinery to actually deliver cancer drugs?" he says. "That's our dream, to go beyond imaging to therapy."
West and Wuest's research has been funded by the Alberta Cancer Foundation, the Allard Foundation, the Dianne and Irving Kipnes Foundation and the Canadian Cancer Society. Both researchers are members of the Cancer Research Institute of Northern Alberta and the Women and Children's Health Research Institute.
