A radiopharmaceutical developed by University of Toronto PhD student Stephanie Borlase is set to play a crucial role in an upcoming clinical trial at Sunnybrook Health Sciences Centre, potentially improving lung cancer treatment. The trial, slated for 2025, will investigate whether focused ultrasound can disrupt the blood-brain barrier, thereby increasing the uptake of immunotherapy into brain metastases—tumors resulting from cancer cells spreading to the brain from other parts of the body.
Overcoming the Blood-Brain Barrier
Immunotherapy has demonstrated promise in treating lung cancer, but its effectiveness is limited by its inability to cross the blood-brain barrier. Borlase's radiopharmaceutical, developed as part of her doctoral research at the Leslie Dan Faculty of Pharmacy, will be used to monitor the delivery of immunotherapy drugs to brain metastases using PET (positron emission tomography) scans.
Borlase has been working on pairing the immunotherapy drug pembrolizumab (Keytruda) with a radioactive isotope that can be imaged by PET. This combination could allow physicians to determine whether the therapy effectively enters the brain and concentrates within tumors following focused ultrasound application.
Development and Manufacturing
For the initial two years of her PhD, Borlase worked in the Centre for Pharmaceutical Oncology’s (CPO) Good Manufacturing Practices facility to prepare the new radiopharmaceutical for clinical trials. Her work involved optimizing and formulating the drug to meet the quality standards required for human use, as well as testing it in pre-clinical models.
Clinical Significance and Impact
Raymond Reilly, director of the CPO, emphasized the significance of this work, stating, "One of the greatest impacts and rewards of pharmaceutical sciences research is to see your work advanced to a clinical trial to make a difference in patient outcomes, which Stephanie has this wonderful opportunity to do."
The trial builds on a previous study where clinicians and scientists at Sunnybrook used a radiopharmaceutical from Reilly’s team to track the delivery of a breast cancer drug to brain metastases. That study provided initial evidence that the technique could improve drug uptake.
Borlase hopes the trial will lead to improved therapies for a notoriously challenging form of cancer. "Even if we cannot completely cure the brain metastases, we can work to prolong survival to give these individuals more time with their families and friends," she said. Borlase recently received a Research Training Award from the Canadian Cancer Society and Brain Canada Foundation.
