PET Imaging: An Emerging Tool in the Fight Against Cancer

As breast cancer awareness month wraps up, it’s a fitting time to take pause and think about all those whose lives have been affected by this life-threatening disease. And, it’s also a time to look forward. Technology is constantly improving, and with it, breast cancer survival rates. Today, doctors are armed with more weapons than ever before, enabling faster, more accurate diagnosis and improved treatment options.

For decades, x-ray mammography has been the standard for breast cancer imaging. In fact, GE Healthcare recently obtained approval to market 3D digital mammography systems in the U.S.  This 3D breast screening technology helps clinicians uncover small cancers which can be a limiting factor in standard 2D mammography.  I’m proud to say that much of the preclinical R&D work occurred right here at GE Global Research.

In addition to x-ray, doctors can now tap into other imaging modalities, like MRI and CT to diagnose cancer and manage treatments. Currently, PET (positron emission technology) scans play a valuable role in treatment by helping clinicians determine if breast cancer has spread to the lymph nodes or other parts of the body, and to assess whether treatment is working.  As the technology advances, PET may enable improved diagnosis and even screening.

Most PET scans use a glucose-like molecule to detect highly metabolic cells, like cancers. I’d like to introduce you to a project I’m working on here at GE Global Research to develop a novel PET imaging agent designed to detect oxidative stress in cells.  One day this technology may allow doctors to make better informed treatment decisions for breast and other cancers.

Cancer is complex
If there is one universal lesson we can take away from decades of cancer research, it is that cancer is extremely complex.  Therapeutic strategies, however, are often guided by relatively simple measures such as the size and location of a tumor or the absence/presence of a biomarker. Genetic and protein expression analysis of surgically removed tumors and biopsy samples can provide insight into the complex nature of cancer, but not the complete picture.  That’s because a single tumor is not a uniform mass of similar cells, it’s a mosaic of cells with differing molecular features and functional properties which are constantly changing as the disease progresses and as therapies are administered.

Imaging should inform us on the complexities of cancer
Biopsies enable the analysis of a tremendous diversity of cancer biomarkers; however the tumor cells being examined have been removed from the body and are no longer a threat to the patient, so these cells may not accurately reflect the remaining tumor. Imaging enables visualization of tumor features while still in the patient allowing doctors to monitor for any change over time. While many imaging agents have been developed targeting various cancer biomarkers, there are very few molecular imaging agents that have become the standard of care in oncology.

In clinical practice, simple measurements are taken from imaging exams to guide diagnosis and treatment.  CT and MRI scans are used for anatomical imaging of a tumor. PET and MRI scans can be used to image functional biomarkers and environmental features of tumors.  Often the results are distilled down to simple metrics like the tumor size (length, in one or two dimensions) or a standardized uptake value.  These metrics influence treatment decisions; however, imaging has the potential to play a much larger role in informing clinicians on the complexities of cancer.  In order to do this there must be a shift from relying on only simple metrics to evaluating high content data from medical images.

High content: imaging more features and getting the most out of every image
Anatomy (CT & MRI) and glucose metabolism (FDG-PET) are workhorse features for cancer imaging. But, in order to get to high content cancer imaging, the medical community will need new technologies that detect additional molecular biomarkers, functions and environmental features. This is where targeted imaging agents come in.  Underneath the surface of each image is a wealth of valuable, extractable information; including hundreds of features related to tumor size, shape, texture and heterogeneity.  This ‘radiomic’ approach to high content imaging is only recently beginning to be tapped into, but will provide additional useful tumor information.

Oxidative Stress PET Imaging
In an effort to enable imaging of different biological features (more content), a team of scientists at GE Global Research is developing a novel PET imaging agent designed to detect a cellular response to oxidative stress. Oxidative stress is caused by an imbalance between the production of toxic free radicals like reactive oxygen and protective cellular antioxidant defenses.  Oxidative stress plays a role in neurodegenerative diseases, heart attack, stroke, and cancer.

The biomarker we are targeting is a molecular transporter that becomes active in response to oxidative stress, which occurs in many cancers.  This transporter is activated as an adaptive response to allow cells to better fight oxidative stress by facilitating the uptake of the amino acid cystine, which is needed in order to make the primary cellular antioxidant, glutathione.  Our oxidative stress PET imaging agent is taken up by cells through this transporter in the same manner as cystine, allowing detection of those cells via preclinical PET imaging.

Oxidative stress results in production of cystine/glutamate transporters, which bring cystine into the cell in exchange for glutamate. Cystine is important for the cellular production of the antioxidant glutathione, which is a primary mechanism for cells to detoxify troublesome reactive oxygen species in the battle against oxidative stress. Our Oxidative Stress PET agent (FASu) is designed to enter cells responding to oxidative stress via this transporter, in a manner similar to the uptake of cystine.

Imaging of this biomarker may someday be useful in highlighting tumor regions with a particularly aggressive nature.  Additionally, this transport system has potential as a therapeutic drug target that could possibly enable selective killing of tumor cells exhibiting this aggressive nature.  For example, “triple negative” breast cancer is associated with a very poor prognosis and limited treatment options.  Our work helps reinforce the potential for a therapeutic drug target expressed in many cancers, including many triple negative breast cancers; which means an oxidative stress PET imaging exam could one day be useful in determining which patients would benefit from such a therapy.  In fact, Dr. Paul Schaffer, a collaborator at TRIUMF (Canada’s National Lab for Particle and Nuclear Physics) in Vancouver, was recently awarded a grant by the Canadian Institutes of Health Research for the preclinical evaluation of our imaging agent in triple negative breast cancer.

Our initial preclinical studies were published in the April 2014 issue of the Journal of Nuclear Medicine.

The Future of Cancer Imaging
In the years to come, I believe that imaging will play an increasingly vital role in cancer care. High content imaging will drive us towards extracting and utilizing more data from every scan. It is my hope that hybrid imaging (like PET/MRI) will become much more than marrying anatomy and functional/molecular imaging; setting us on course to maximize the amount of relevant data and value from every imaging exam. And, I think that our contribution to PET imaging will be one of many crucial developments aimed at giving the medical community a leg up in the fight against cancer.  This month, as we keep those who’ve been impacted by breast cancer in our thoughts, I hope you’ll be inspired by the promise technologies like ours hold to help save lives.


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