Research at LMIR (Reilly laboratory at the Leslie Dan Faculty of Pharmacy, University of Toronto) focuses on the discovery, preclinical development and clinical translation of novel radiopharmaceutical probes for molecular imaging of cancer as well as molecularly-targeted radiotherapeutics for cancer. Molecular imaging is a powerful state-of-the-art imaging modality which probes the biology of tumours to permit their detection, but most importantly reveal their phenotypic properties. The laboratory exploits the overexpression of peptide growth factor receptors on cancer cells and their recognition by highly specific monoclonal antibodies or peptide receptor ligands to devise imaging probes for tumour detection by single-photon-emission-computed tomography (SPECT) or positron-emission tomography (PET). Additionally, we explore the potential of using molecular imaging to predict or monitor the response of tumours to targeted cancer therapies.
An extension of molecular imaging is the application of radiopharmaceuticals for the treatment of cancer (targeted radiotherapy). A major research thrust is to exploit the nanometer-micrometer range Auger electrons emitted by 111In to cause single-cell killing of tumour cells without significant toxicity to normal cells. To achieve this, we employ monoclonal antibodies and peptides to target 111In to cancerous cells and mediate their internalization, then route them to the nucleus of the cells with nuclear-localization peptide sequences (NLS), where the emitted Auger electrons are most damaging to DNA and lethal [Auger electron radioimmunotherapy (RIT)]. We are also exploring the use of the millimetre-range beta-particle emitters, 177Lu and 64Cu conjugated to monoclonal antibodies for RIT of breast and pancreatic cancer. 64Cu is also a positron emitter which may permit combined PET imaging and RIT ("theranostic approach"). Finally, we are exploring the application of molecularly-targeted gold nanoparticles labeled with 177Lu or 111In for localized radiotherapy of breast cancer.
Our mission is to translate the most promising imaging or targeted radiotherapeutic agents discovered in the laboratory to Phase I clinical trials in cancer patients at the University of Toronto affiliated hospitals. We have successfully achieved this for three agents to date with a fourth agent currently under development. Thus, educational opportunities for students and trainees encompass radiopharmaceutical chemistry, preclinical evaluation in small animal tumour models including microSPECT and microPET imaging, formulation of pharmaceutical quality radiopharmaceuticals, and the design and conduct of clinical trials of new agents for imaging or treatment of malignancies. Opportunities exist for university-industry collaborations for companies interested to pursue joint projects with the laboratory.
An extension of molecular imaging is the application of radiopharmaceuticals for the treatment of cancer (targeted radiotherapy). A major research thrust is to exploit the nanometer-micrometer range Auger electrons emitted by 111In to cause single-cell killing of tumour cells without significant toxicity to normal cells. To achieve this, we employ monoclonal antibodies and peptides to target 111In to cancerous cells and mediate their internalization, then route them to the nucleus of the cells with nuclear-localization peptide sequences (NLS), where the emitted Auger electrons are most damaging to DNA and lethal [Auger electron radioimmunotherapy (RIT)]. We are also exploring the use of the millimetre-range beta-particle emitters, 177Lu and 64Cu conjugated to monoclonal antibodies for RIT of breast and pancreatic cancer. 64Cu is also a positron emitter which may permit combined PET imaging and RIT ("theranostic approach"). Finally, we are exploring the application of molecularly-targeted gold nanoparticles labeled with 177Lu or 111In for localized radiotherapy of breast cancer.
Our mission is to translate the most promising imaging or targeted radiotherapeutic agents discovered in the laboratory to Phase I clinical trials in cancer patients at the University of Toronto affiliated hospitals. We have successfully achieved this for three agents to date with a fourth agent currently under development. Thus, educational opportunities for students and trainees encompass radiopharmaceutical chemistry, preclinical evaluation in small animal tumour models including microSPECT and microPET imaging, formulation of pharmaceutical quality radiopharmaceuticals, and the design and conduct of clinical trials of new agents for imaging or treatment of malignancies. Opportunities exist for university-industry collaborations for companies interested to pursue joint projects with the laboratory.