[Triumf-seminars] TRIUMF Colloquium today at 14:00

[TRIUMF Seminars]

Date/Time: Thu 2023-05-11 at 14:00

Location:  Auditorium/remote   

Speaker:   Raymond M. Reilly (University of Toronto)

Title:     Radiation Nanomedicines for Treatment of Triple-Negative Breast Cancer (TNBC) and Glioblastoma Multiforme (GBM)

Abstract: Radiation nanomedicines are composed of gold nanoparticles (AuNPs) modified with metal-chelating polymers that complex radionuclides emitting short-range beta-particles. In this presentation, I will describe two promising applications of radiation nanomedicines for cancer treatment – one aimed at local treatment of triple-negative breast cancer (TNBC) and a second aimed at treatment of glioblastoma multiforme (GBM). For TNBC, AuNPs labeled with 90Y were embedded into a calcium alginate seed (nanodepot) which was implanted intratumorally into 4T1 murine mammary carcinoma TNBC tumours in immunocompetent Balb/c mice. The tumour growth-inhibitory effects on this tumour were evaluated and the radiation nanomedicine was combined with anti-PD-L1 checkpoint immunotherapy to investigate an abscopal effect on a distant 4T1 tumour outside the range of the beta-particles. SPECT/CT imaging and biodistribution studies were performed. The radiation doses to tumours and normal organs were estimated. Normal tissue toxicity was assessed. For local treatment of GBM, AuNPs complexed to 177Lu were infused into U251-Luc human GBM tumours in the brain in NRG mice. SPECT/CT was used to image retention of 177Lu-AuNPs in the tumour while bioluminescence imaging (BLI) and MRI were used to assess tumour growth inhibition. Kaplan-Meier median survival of treated and control mice was determined. Our results showed that 90Y-labeled AuNPs strongly inhibited 4T1 tumour growth in mice and caused an abscopal effect on a distant tumour, which was enhanced when combined with anti-PD-L1 immunotherapy. There was no normal tissue toxicity and doses to the treated tumour were high (500 Gy) while normal tissue doses were low (<1 Gy). Similarly, in mice with GBM, 177Lu-AuNPs were retained in the the tumour with minimal redistrbution to normal brain or other organs. Radiation doses in GBM tumours were high (600 Gy) while doses in normal brain were >100-fold lower (<6 Gy). There was no normal tissue toxicity. MRI showed no evidence of GBM in mice
 treated with the radiation nanomedicine but large GBM tumours in control mice receiving unlabeled AuNPs or no treatment. The median survival of mice treated with 177Lu-labeled AuNPs was >4-fold longer than control mice. These two studies demonstrate the potential of radiation nanomedicines for local treatment of tumours without normal tissue toxicity. Future research in this area will be discussed.

For people who join remotely:  
Topic: TRIUMF Colloquium -- Dr. Raymond M. Reilly
Time: May 11, 2023 02:00 PM Pacific Time (US and Canada)

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Dr.