The thought of medicine mixing with radioactivity may not leave you with the best feeling in your stomach, but researchers at U of T are doing just that, using radioactive particles to develop novel advances in the field of therapeutic medicine.
Professor Raymond Reilly, the principal investigator at the Lab of Molecular Imaging and Targeted Radiotherapeutics (LMIR) in the faculty of pharmacy, focuses on using radiation-emitting pharmaceuticals (radiopharmaceuticals) to detect and treat cancers.
“[Radiopharmaceuticals] are much more focused and biologically-targeted than external radiation,” Reilly explained. Radiation has been used in the treatment of cancer for over a century, but radiopharmaceuticals offer more effective treatment possibilities.
One part of Reilly’s research deals with Trastuzumab (sold as Herceptin), an expensive new drug for breast cancer that costs about $50,000 a year. The problem with Herceptin is that not all patients respond to it, a discovery to be made only after paying thousands of dollars for a treatment that does not even touch the tumour.
Reilly is developing radio-labeled Herceptin-the same drug but attached to a radioisotope that can be detected on a scan-so that he can track the drug to see if it will reach the tumour. If Herceptin successfully targets cancer in a certain patient, then Herceptin treatment may also be effective. If it doesn’t work, other treatment options can be investigated for that patient.
“Treatment and diagnostics are on a continuum,” Reilly said. “A diagnostic imaging radiopharmaceutical can be used for treatment by changing the isotope or by increasing the dose.”
Reilly has gone from words to action. He is working on a radio-labeled form of Herceptin for treatment of breast cancer tumours, turning a tracking device into a more effective drug. This drug would target tumours in two approaches: the growth-inhibiting properties of the basic drug (Herceptin) and the cell-killing properties of the radioisotope label. In preliminary findings, the radio-labeled Herceptin is more effective at suppressing and destroying breast cancer cells in laboratory cell cultures than its non-radio-labeled counterpart.
Perhaps one of LMIR’s biggest successes is the development of a radiopharmaceutical currently in clinical trials. This novel drug is based on a normal hormone system that cancer cells are particularly sensitive to. Epidermal growth factor (EGF) is a hormone that normally stimulates cells to grow and divide. Like all hormonal systems, the body regularly needs to shut off the growth signal as part of its everyday cycle. In order for this to happen, EGF must be directly taken into the cell and degraded. Reilly has found that coupling an EGF molecule to a radioisotope that emits very short-range electrons is lethal to cells. When the molecule is pulled into a cell for routine degradation, the attached radioisotope emits its electrons and kills the cell from within.
“This is like the Trojan horse legend, but in a radiopharmaceutical context,” Reilly said. The group has found that breast cancer cells, which use more EGF than normal cells, are particularly sensitive to the radio-labeled EGF.
Appropriately enough, in order to administer any investigational drugs to patients, Reilly must receive approval not only from Health Canada but also from the Canadian Nuclear Safety Commission.
“One of the things about nuclear medicine is that it is not very well-known,” he said. “The big difference [between] military use of radioactivity and medical use of radioactivity is that we use radioisotopes that are much shorter-lived, so we don’t have issues of nuclear waste.”
Radioisotopes in medicine have a maximum half-life-the time it takes for the quantity to degrade to half of its original value-of several days to one week. Some exceptionally short-lived species of radioisotopes in the field are the positron-emitters whose half-lives range from mere minutes to a few hours. This translates into essentially indiscernible levels of radiation after a few days.
“Another general thing is that a lot of people are cautious about radioactivity because we are capable of measuring it very easily and so we are more aware of it as a hazard,” added Reilly. For researchers, the fact that radioactivity can be measured acutely means that it can be contained more easily. (The same cannot be said for other environmental hazards, like greenhouse gas emissions, where atmospheric levels cannot be determined to a precise degree.)
The field of nuclear medicine is a growing one and will be increasingly important in the general pharmaceutical industry. Reilly hopes to improve the treatment other types of cancers by developing more targeted therapies in the near future.
“At some point, we hope that we won’t be using the same chemotherapy drugs that we have been using for the last thirty years,” Reilly said. “We really need better treatment.”
