Raymond Reilly, University of Toronto
Project Title: “Radiation Nanomedicine for Intraoperative Treatment of Glioblastoma Multiforme (GBM)”
In this project, we will study for the first time a new radiation nanomedicine for local treatment of glioblastoma multiforme (GBM) that could be administered at surgery in order to prevent tumour recurrence. The radiation nanomedicine is composed of gold nanoparticles (AuNPs) labeled with radioisotope, lutetium- 177 (177Lu) that emits short range radiation. The radiation nanomedicine is expected to eradicate small tumour deposits that the surgeon is unable to remove, but the short range of the radiation should also minimize normal brain toxicity. Although the surgeon aims to remove the entire brain tumour, any cancer cells that remain cause recurrence of GBM, and death from GBM. Our hope is that this radiation nanomedicine will present tumour recurrence. This approach to local treatment of brain tumours has never been previously studied. We will test the idea in mice implanted with human GBM in the brain that are treated by local administration of the radiation nanomedicine.
The effectiveness and normal tissue toxicity (including the normal brain) will be assessed. Our team includes neurosurgeons, Dr. James Rutka who treats GBM, thus if we are successful, we plan to advance this radiation nanomedicine to a Phase 1 clinical trial in patients with GBM.
What receiving this award means to Raymond:
“My research team is tremendously excited to receive support from Brain Tumour Foundation of Canada. This support will allow my team to test a new idea for preventing recurrence in patients with glioblastoma multiforme (GBM), which is one of the most difficult to treat and unfortunately one of the most common forms of brain cancer. Despite surgery, radiation and chemotherapy, recurrence remains a major challenge in treating GBM, contributing to the poor outcome in patients. We plan to study a new local form of radiation called a radiation nanomedicine that could be administered locally at the time of surgery to eradicate any remaining tumour and reduce the risk of recurrence. We could not study this new radiation nanomedicine without the support of Brain Tumour Foundation of Canada.”
UPDATE: October, 2020
This research project aims to develop a new radiation treatment for glioblastoma multiforme (GBM) called a radiation nanomedicine that could be infused at surgery into the brain to eradicate any tumour that the surgeon is unable to remove.
The long-term goal is to reduce the risk for recurrence of GBM and thereby improve the longterm outcome of patients with this very poor prognosis form of brain tumour. In the first year of the project, we synthesised the radiation nanomedicine and studied its retention in human GBM tumours implanted into the
brain in mice. The radiation nanomedicine was strongly retained in the brain tumour and did not re-distribute into the normal brain or to normal organs outside the brain.
This is a very promising finding since it means that the radiation nanomedicine will deposit radiation only in the tumour and not in the normal brain or other normal
organs, which should maximize its effectiveness for treatment of GBM, while minimizing any toxicity to the normal brain or normal organs.
Indeed, we conducted a study in the past year to evaluate the normal organ
toxicity of the radiation nanomedicine, which showed no evidence of toxicity against any normal organs. We still need to study if the radiation nanomedicine has any toxicity against the normal brain, but this is not expected due to the local retention in the tumour. In the second year of the project, we will study the effectiveness of the radiation nanomedicine for treating human GBM tumours in mice and examine the toxicity on normal brain.
The project is on track. In addition, the support of the BTFC has allowed us to be successful in obtaining additional major funding from the Canadian Cancer Society as an Innovation Grant (2020-2022) to extend the idea to another radioisotope, mercury-197 that emits a different type of radiation (Auger electrons) and combine the radiation nanomedicine with immunotherapy for treatment of GBM.