Getting the Complete Picture of Cancer

In the same way that cancers differ from one person to another, cancer cells within a single tumour can behave differently from each other. This is due in part to variations in the microenvironment within individual tumours. For example, the availability of oxygen and nutrients varies from one region of a tumour to another. In areas of poor oxygenation, or hypoxia, tumour cells become resistant to therapy and can acquire more aggressive features that enable them to metastasize and regrow following treatment. It is thus important to understand the complete environment of individual cancers, and to develop therapies that will effectively treat all cells in the tumour.

This complexity, however, does not discourage us in our fight to conquer cancer. On the contrary, it motivates us to understand its sophistication, and to create therapies that are tailored to each tumour’s specific composition and vulnerabilities. In order to do this, we must be able to obtain a clear picture of the cancer disease spectrum, and to develop therapies that will be effective in each.

Molecular imaging (MI) is a rapidly evolving field within cancer therapy, which offers clinicians and researchers a noninvasive, real-time approach to visualize and quantify how the body is functioning at the molecular and cellular level. Using technologies such as Positron Emission Tomography (PET) scanning, which can be used to detect specific properties of cancer cells based on the localization of molecular tracers, MI provides a detailed characterization of the body’s biological processes, which opens the door to new, never-before seen, cancer targets through which we can combat the disease.

Molecular Imaging: A Multidisciplinary Field

Molecular imaging (MI) is a multidisciplinary field, requiring collaboration amongst many areas of science – including molecular biology, biochemistry, physiology, physics, genetics, mathematics and more.

The STTARR Facility, located in The Princess Margaret Cancer Research Tower, is a state-of-the-art imaging centre which provides a platform for cutting-edge multidisciplinary research in MI that is unmatched anywhere in the world.

In addition, The Princess Margaret is fortunate to be part of the Joint Department of Medical Imaging (JDMI) – the largest sub-specialty imaging department in Canada, spanning University Health Network (UHN) hospitals, Mount Sinai Hospital, and Women’s College Hospital. Under the leadership of Dr. Lawrence White, the department is continuously evolving to meet international best practices and technology standards. At The Princess Margaret alone, over 80,000 imaging studies are performed annually through the JDMI, ranging from neurological imaging to breast imaging to musculoskeletal imaging.

The Importance of Molecular Imaging for Patients

Molecular imaging plays a critical role in personalizing many facets of cancer care:
• Early and accurate diagnosis (tumour localization, sensitivity, tumour profiling, 3D mapping of disease);
• Selection of therapies (drug target expression, dose optimization);
• Quantitative and early measurement of response to therapies (early response evaluation, early detection of relapse);
• Theranostics (combined diagnostics and therapies). In the sections below, we outline some of the most recent initiatives in MI that we are particularly excited about at The Princess Margaret.

Predicting Tumour Response using Hypoxia Imaging

Just as humans are the product of a complex interplay between their genes and their environment, so too are cancers. Under the guidance of Dr. Bradly Wouters, Interim Research Director at The Princess Margaret, our researchers are paving the way in understanding the role of a tumour’s microenvironment (i.e. its cellular environment) in promoting tumourigenesis (tumour development) and resistance to therapy.

Of particular importance to our scientists is the study of oxygenation levels in the tumour environment. Whereas the majority of tissues in our body are kept at uniform oxygen levels, it is common amongst tumours to have regions of deprived oxygen, known as hypoxia. This hypoxia has proven to be a strong predictor of response, often indicating that a tumour will be aggressive and resistant to therapy.

Understanding why hypoxia and other metabolic features of the microenvironment cause tumours to become more aggressive will pave the way to develop more effective therapies for patients.

Our Institute is among the top three institutes in the world studying tumour hypoxia and includes a large and diverse team of scientists and clinicians translating discoveries from bench to bedside. The team continues to strive to understand at the most fundamental levels why hypoxia causes aggressive tumour growth and treatment resistance, and then uses this understanding to develop new ways to target these cells in combination with other effective therapies.

The Princess Margaret has been leading the development of an image-based hypoxia measurement system that enables physicians to accurately quantify oxygenation levels in patients. Quantifying the degree of tumour hypoxia in individual patients will help guide future cancer therapy decisions and will help inform the selection of cancer patients for clinical trials of new hypoxia-targeting interventions.

Given planned and ongoing application across six clinical disease sites, we are rapidly becoming one of the largest hypoxia imaging sets in the world. The imaging team is working in close collaboration with the cancer genetics team to incorporate imaging and genetics for personalized therapy.

Imaging for Guided Therapy

The Guided Therapeutics (GTx) Program, under the leadership of Techna Institute Director Dr. David Jaffray, is a research platform dedicated to the integration of modern technologies, such as imaging and robotics, with therapy. This program is an excellent example of how molecular imaging can lead to more successful interventions, and fewer therapy side effects.

A) Optical Contouring Technology
Approximately half of cancer patients require radiation therapy at some point during their cancer journey. However, defining the location of radiation targets (i.e. the boundary of the tumour to be removed) can be a major difficulty amongst radiation oncologists. This can be detrimental to a patient if part of the tumour is missed by the radiation, or if the target is too large and unnecessarily irradiates normal tissue.

To resolve this challenge, our scientists at the Techna Institute have designed and built a new software platform to improve optical contouring of tumour boundaries. This optical contouring can be an especially powerful tool in defining head and neck tumours. We have tested this strategy in pre-clinical models, and have seen improvements in defining the tumour boundary by several millimeters.

B) Image-Guided Surgery
To improve surgical procedures in the OR, Drs. David Jaffray and Jonathan Irish and their teams have created a system that alerts a surgeon when he or she is cutting too close to tissue that should be avoided, like a carotid artery or a major nerve.

This innovative technology utilizes visual maps for surgical guidance, and integrates visual, auditory and tactile queues to alert surgeons if they are cutting too close to these important structures.

C) The GTx Operating Room (GTx-OR)
The GTx-OR is a groundbreaking, 1,200 square foot research operating room that is the first of its kind in the world. This unique space, developed at The Princess Margaret, integrates the newest innovations in multimodal image-guidance systems, featuring: a multi-detector CT scanner, a high-performance ultraosound, fluorescence imaging, and more. It will also incorporate robotic surgery in the near future. It supports minimally and ultra-minimally invasive surgeries that, for some patients, can offer surgery without incisions.

The GTx-OR had its first productive year in operation as of July 2014, and the team has treated over 40 patients with lung, head and neck cancers, and also perform cardiac and vascular surgery. This year, the team will also begin pre-clinical work in gynecological and hepato-pancreatic-biliary cancers and sarcoma.

Nanoparticles: The Development of a New Theranostic Agent

We are extremely excited about a recent discovery by The Princess Margaret’s Dr. Gang Zheng, who combined two naturally occurring substances to create “nanoparticles.” These nanoparticles (image below) are less than 100 nanometers in size, and are engineered to be attracted to cancer cells.

The incredible thing about Dr. Zheng’s nanoparticle discovery is that these particular particles can be filled with drugs to treat the tumour being targeted, while sparing surrounding healthy tissue. On top of this, they have the ability to absorb light, and upon irradiation with laser light, they can rapidly heat up and destroy the tumour.

Dr. Zheng’s nanoparticle can also be utilized as an imaging agent for positron emission tomography (PET), which will allow clinicians to visualize nanoparticle distribution in the body. This will serve as an invaluable tool for clinicians, enabling them to localize where drugs are being targeted, to determine how drugs are being released, and to confirm that the therapy has been effective.

These nanoparticles are an excellent example of a theranostic agent – a therapy that is multifunctional, and can provide “one-stop shopping” for cancer treatment and imaging.

Your Support

At The Princess Margaret, we are determined to provide our patients with the gold standard of care through Personalized Cancer Medicine. Given its critical role in personalizing many facets of cancer care, molecular imaging and the investigation of how the microenvironment influences cancer biology has been, and will continue to be, a key area of focus for our clinicians and scientists.

This work requires investments in innovative imaging instruments, such as combined Positron Emission Tomography and Magnetic Resonance Imaging scanners (PET-MRI), as well as facilities and equipment to enable the visualization of molecular imaging agents. Moreover, it requires funding for basic research and drug development that will enable more effective personalized treatments in individuals with unfavourable tumour characteristics.

Molecular imaging and pre-clinical work happening in the GTx OR represent key elements in the future of cancer therapy, and we need your help to support these ground breaking initiatives.

For more information, please contact:
Christy Morrow, CFRE
Associate Director, Major Gifts
The Princess Margaret Cancer Foundation
Tel: 416.946.2107
Email: [email protected]