Spying on cancer from the inside of the body

Frank Wuest's work with radiotracers reveals how tumour cells behave at the molecular level, to advance personalized cancer diagnostics and treatment.

Laura Vega - 10 May 2017

One of the main reasons why some cancerous tumours are so threatening is how challenging it can be to detect them-you cannot treat what you cannot see. Even once a tumour is identified, how particular cancer cells will develop or respond to a specific treatment can be unpredictable, uncharted territory.

Frank Wuest and his team are approaching their research to improve cancer detection and treatment with the help of radiopharmaceutical sciences, focused on designing and producing chemical compounds decorated with a radioactive atom-called radiotracers-that can be released into the human body to detect cancer and other diseases.

"I call them 'metabolic spies'," explains Wuest. "These compounds are introduced into patients for us to monitor cancer cells and understand what makes these cells so different from others. We want to look into the inside of the body to identify these cells and the disease at a very early stage."

Helping defeat cancer with personalized treatment

Wuest is a biochemist in the U of A's Department of Oncology, and the Dianne and Irving Kipnes Chair in Radiopharmaceutical Sciences. Originally from Germany, he was drawn to Edmonton's University of Alberta nine years ago by the opportunity to build an innovative cancer research program.

During his tenure to date, Wuest has cemented the foundations of an ambitious and experimental cancer research project that promises to make a deep impact on disease prevention and patient care. The research focus of his team follows one clear mantra: "Selecting the right patient for the right treatment at the right time."

While common diagnostic tools like MRIs can illustrate where a tumour is located, radiotracers can provide more information about how the tumour cells behave and how their metabolism works.

"There are so many cancer treatment opportunities. We want to monitor how patients respond to certain treatments and make sure each patient receives the most optimal treatment option for them."

Wuest's team learned that about 20 to 30 per cent of all breast cancer patients have tumours with a particular type of metabolism. The researchers have developed a fructose derivative to monitor this particular metabolism and hope to begin clinical trials for its use soon.

This specialized research may eventually personalize cancer treatment by identifying a tumour's "molecular signature," and allowing the application of precise therapies specific to it. "This could allow patients to avoid undergoing treatments that will be unnecessary or ineffective for them. It's like a 'key and lock' principle," explains Wuest. "We design molecular 'keys' which fit perfectly into a molecular 'lock' and it gives us the necessary information for visualizing the tumour cells at an early stage."

He adds that radiopharmaceuticals show a great deal of potential in the detection and treatment applications for many types of tumours including prostate cancer, and for neurodegenerative diseases like Alzheimer's.

Better diagnosis for more patients

Because of the radiotracers' short half-life, Wuest's team works with highly sophisticated equipment to produce them daily as needed, in what he calls a "radiopharmacy on demand." The team uses a cyclotron (a particle accelerator, which acts similarly to a nuclear reactor on a much smaller scale) to prepare the radionuclides or radioisotopes that are part of the basic components, and the most intricate part of the process is the actual synthesis and manufacturing of the radiotracers.

The need for complex procedures, costly infrastructure and specialized personnel to manufacture the compounds limits the production only to facilities that have the right technology. Currently, the Cross Cancer Institute is the only facility capable of producing these substances in Alberta, but Wuest's team is currently working on an innovative idea to allow their "spies" to eventually reach more patients.

The Dianne and Irving Kipnes Chair in Radiopharmaceutical Sciences was established in 2012 with generous funding from Dianne and Irving Kipnes through the Alberta Cancer Foundation. The research Chair aims to designate a scientist that provides leadership in the development of world-class radiopharmaceutical sciences research program within the University of Alberta Institutes and expanding to provincial initiatives.

In addition to the funding received through the Kipnes Chair, Wuest's team has received support from NSERC, CIHR, Canadian Breast Cancer Foundation and Alberta Heritage Foundation for Medical Research, among others. The research that supports the radiotracer kits has been partly funded by the Prostate Cancer Foundation, and they have also received funding from the University Hospital Foundation Medical Research Competition for a project on molecular targeting of proteins regulating cell growth in papillary thyroid cancer.

The research group has developed a concept of portable "kits" that would reduce the radiopharmacy to a small vial which contains all the ingredients necessary to produce the compounds. By adding the radionuclide to this special chemical mix, personnel from centres could produce their own radiotracers.

This project is a joint effort together with Ralf Schirrmacher-also from the Department of Oncology-who developed the basic chemistry concept that was used as a foundation for the synthesis of these compounds.

"Currently, most patients have to come here to get that special diagnosis," says Wuest. "We can distribute radionuclides without a problem, and also distribute these kits to many other places, like smaller hospitals, nuclear medicine departments with smaller labs, and they can produce the compounds in these little vials."

The kits are still in early stages of development, but could potentially improve cancer diagnosis and monitoring throughout Canada.

"We want to shift to a 'decentralized pharmacy' concept, and this seems to be a very promising start," adds Wuest.

Advancing through support and collaboration

For Wuest, collaborative work and support from funding partners have been key to moving his research forward.

"We still have a lot to learn about basic cancer biology, and right here, at the University of Alberta, is one of the best places to do that," says Wuest. "We have strong links to other departments like chemistry and biology, and to other research hubs within the Faculty of Medicine & Dentistry. Here at the Cross Cancer Institute we have very strong experimental oncology research. Under the umbrella of the Cancer Research Institute of Northern Alberta (CRINA), we aim to intensify collaboration with physicians, clinicians and oncologists, especially at the Cross Cancer Institute, to provide the platform to introduce these tracers into a clinical application and ultimately improve patient care."

"Currently I think we are probably the most specialized facility in translational cancer research in western Canada," adds Wuest.

He has also designed a new oncology course to train medical students in the most current applications of molecular imaging.

Wuest is grateful for all the help received along the way and hopes to expand this support for the clinical trials phase. In the meantime, he continues to develop these special "spies" hoping to make a difference in patients' lives.

"When you walk into a cancer hospital like the Cross Cancer Institute every morning, you see why cancer research is important. You see the challenges for the patients and their families, and their success stories as well. It's very rewarding to feel that you are a part of that."