Let There be Light

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By Mary Sanchez

There are some bright ideas emerging from Canada.

A growing number of Canadian labs and companies are using light to treat and detect disease, including cancers and inflammatory diseases.

This emerging sector, called biophotonics, uses the properties of photons to generate unique interactions with living tissue. The result of the convergence of biology and photonics, biophotonics, put simply, is when living tissue and biomolecules are involved in the generation, transmission and detection of light.

Biophotonics encompasses devices and procedures for diagnostics or therapeutics that are geared towards non- or minimally invasive treatment, diagnosis or understanding of disease using various forms of light-tissue interactions. In diagnostics, for example, researchers can send photons to any point in the tissue and get information without having to do a biopsy. On the therapeutics side, scientists can localize treatment to a small area by using photodynamic therapy (PDT) — the use of light-activated drugs called photosensitizers — rather than a systematic treatment like chemotherapy, which affects the entire body.

Canadian Pioneers

Perhaps the biggest success that Canada has seen from a biophotonics application is from Visudyne®, which has already enjoyed commercial success for the treatment of age-related macular degeneration — the leading cause of blindness for people over the age of 50. Available in almost 60 countries, Visudyne is the largest-selling ophthalmology product ever launched, and one of the fastest-growing biopharmaceutical products in history.

Visudyne is the brainchild of Drs. Julia Levy and David Dolphin. It would be a fair assumption to say that anybody who is anybody in this industry is familiar with at least the names, if not the work, of Levy and Dolphin. The scientists are renowned for their work in PDT. Levy, the co-founder and former president and CEO of Vancouver’s QLT Inc., is well-known for co-inventing PDT, which led to the invention of QLT’s first-generation product for the treatment of cancer, Photofrin®, and Visudyne, which was discovered in her lab. Dolphin, a world-renowned expert in porphyrin chemistry and biochemistry, was instrumental in the co-discovery of the family of photosensitive compounds that led to the development of Visudyne. Due to the success of the anti-blindness drug, QLT has grown from a startup to one of about 14 profitable biopharmaceutical companies out of a field of over 400 worldwide. In fact, Levy and Dolphin are the 2002 recipients of the Friesen-Rygiel Prize — awarded annually to the partners credited with the creation of a commercial enterprise from an outstanding discovery generated in a Canadian academic institution.

On the diagnostics side, Canada is home to the developers of the only U.S. FDA-approved fluorescence-imaging device. Vancouver-based Xillix Corp. — a company focused on the research, development and commercialization of medical imaging technologies to aid in the early detection and localization of cancer — is responsible for the LIFE-Lung Fluorescence Endoscopy System™. In clinical trials, lung cancer detection rates improved by more than 171% with the LIFE-Lung system, compared to conventional white light bronchoscopy. Today, Xillix is improving upon its fluorescence endoscopy technology through the development of its third-generation product, Onco-LIFE™, for the detection of both lung and gastrointestinal (GI) cancers. The technology detects and localizes abnormal tissues, which fluoresce differently than normal cells, so doctors will know where to do a biopsy.

Also developed by a Canadian company, Theralux™ is an ex vivo photodynamic treatment device targeting cancers affecting bone marrow, graft-versus-host disease and certain autoimmune diseases. Created by Montreal-based Theratechnologies Inc. and transferred to the company’s subsidiary, Celmed BioSciences, in June 2001, Theralux is meant to restore the normal function of the marrow of patients who have undergone chemotherapy. In the Theralux process, stem cells are withdrawn from the patient, and are then treated with the photosensitive molecule TH 9402 and a light source to eradicate the cancerous cells, while preserving an adequate number of healthy cells. Then, the treated cells are reinfused into the patient who has undergone chemotherapy. In preclinical research, Theralux has been shown to prevent rejection problems, while preserving the immune response and the anti-cancer effect that is sought in bone marrow transplants.

Lighting the Way

A real contribution to the country’s capabilities in biophotonics is the 2,500-square-foot Biophotonics Facility, which is jointly operated by the Ontario Cancer Institute (OCI) and Photonics Research Ontario (PRO). Research taking place within the biophotonics program is both for cancer and non-cancer applications, including: PDT; image-guided, minimally invasive therapies; non-invasive optical diagnostics; and confocal laser scanning technologies. The facility is home to the research of some big names in biophotonics.

Say the name Brian Wilson and most scientists know that you’re not referring to the ex-Beach Boy, but rather an OCI scientist involved in the development and application of new therapeutic and diagnostic techniques based on the use of lasers and other optical technologies. The head of the Division of Medical Physics at the OCI, Wilson is using animal models to study the relationship between tissue and light in therapeutic and diagnostic techniques. On the therapeutic side, Wilson and his team are using PDT as a method for selective destruction of solid tumours, with a focus on malignant brain tumours. His research involves the induction of intracranial tumours in an animal model, followed by PDT treatment and quantitative histopathology and biochemical analysis of resected tissues to determine the fundamental PDT sensitivity of the tissue-photosensitizer combination. The team has found that one photosensitizer (5d-aminolevulinic acid, a heme precursor) has an extremely high sensitivity in tumours compared to normal white matter in the brain.

On the diagnostic side, Wilson’s group is investigating tissue fluorescence — the re-emission of longer wavelength light by a molecule after absorption of a shorter wavelength photon — as a possible method for early cancer detection during endoscopy of the GI tract. The data resulting from the group’s research will form the basis for developing imaging algorithms to be used in a real-time fluorescence endoscope, a prototype that is undergoing initial clinical trials.

Dr. Michael Sherar, also with the OCI, is looking into the use of lasers for thermal therapy as a treatment for various cancers. This involves using light to heat up and then kill cancer cells in a tumour, while sparing healthy, normal cells. Sherar’s lab is also using light to develop and test methods of image guidance for monitoring thermal therapy during treatment to ensure the safety and efficacy of the procedure.

Dr. Lothar Lilge, a staff scientist with the University Health Network and an assistant professor with the University of Toronto, is also involved in PDT. The former director of the Biophotonics Facility is designing new protocols and tools to increase the efficacy of treatment, with a focus on brain and prostate cancers. On the diagnostic side, Lilge is using transillumination spectroscopy combined with numerical biostatistical methods to quantify the risk of cancer. For example, Lilge explains, his group is using white light to do transillumination of the breast tissue to see if they can somehow quantify a breast cancer risk. Lilge is also using light as a tool for biomedical research. This includes using optical tweezers, optical scissors, chromophore-assisted laser inactivation and capillary electrophoresis to sort, manipulate and detect cells, proteins, DNA and mRNA.

At the Hamilton Regional Cancer Centre, Dr. Mike Patterson, head of the Medical Physics Department, is conducting research into the dosimetry of PDT.

“We’re trying to develop instruments and tools and theories to help us predict what the biological effect of a PDT treatment will be,” Patterson says.

Currently, he explains, all patients are given the same dose of the PDT drug and the same amount of light.

“But we know there are individual variations in how much of the drug goes to the tumour, and there are differences in the optical properties of the tissue. So, how well the light penetrates is different from individual to individual,” he explains. He adds that his lab is developing a non-invasive optical measurement using optical fibres that could be put on the tumour or the tissue that’s going to be treated. The measurement would tell how much of the photosensitizing drug is actually in the tissue. So, rather than relying on the dose that was injected into the patient, Patterson and his team could measure the tumour to find out how much of the drug found its way to the tumour.

In a lab at the University of Waterloo, Ted Dixon is developing applications for the fluorescence imaging of protein gels and DNA sequencing gels, and fluorescence imaging for cancer detection.

“We have a laser scanning system that scans a laser beam across a specimen. We then look at the fluorescence that comes back from the specimen and we form a high-resolution image in fluorescence,” explains Dixon. “One of the reasons for imaging tissue, say from biopsy specimens, is that in fluorescence you can outline the areas that are cancerous.”

In addition, he explains, tissue imaging allows scientists to see the physical effect of a drug on the human body.

“So you can take an image before a drug is given and then wait for some time after and see what change has occurred in the tumour and so forth,” he says.

Calling for Sunshine

Although the biophotonics industry is still in its infancy, it has enormous potential and is really only beginning to be investigated. According to Photonics Research Ontario, the global market for biophotonics technologies will reach $8 billion US by 2005, up $6.8 billion US from 2000.

Canada has already made a significant contribution to the biophotonics industry with the commercialization of QLT’s Visudyne and Xillix’s U.S. FDA-approved LIFE-Lung system. And the hope is that the country’s contribution to biophotonics research will continue to grow.

Indeed, the future for biophotonics in Canada looks bright.