Director, Centre for Pharmaceutical Oncology
Molecular Imaging and Targeted Radiotherapy of Cancer
Our research focuses on the discovery, preclinical development and translation to Phase I/II clinical trials of novel radiopharmaceuticals for molecular imaging and targeted radiotherapy of cancer.
Molecular Imaging is a powerful new imaging modality which probes the biology of tumours to permit their detection, but most importantly reveal their phenotypic properties. Molecular imaging which includes SPECT and PET nuclear medicine technologies has great potential for cancer detection as well as predicting and monitoring response to treatment, especially to new molecularly-targeted drugs (e.g. Herceptin). Our approach focuses on imaging the over expression of peptide growth factor receptors (e.g. EGFR, HER2 or IGF-1R) since these are often the targets for these drugs. In addition, we are interested in imaging leukemia stem cells using radiolabeled anti-CD123 antibodies; imaging of cytolytic vaccinia virus delivery to tumours using radiolabeled octreotide analogues, and imaging the tumour and normal tissue distribution of micellar drug delivery systems. In addition, we are conducting a Phase I/II clinical trial of radioimmunoguided surgery (RIGS) of breast cancer using radiolabeled trastuzumab Fab antibodies directed against HER2 which aims to improve the surgical management of the disease.
Targeted Radiotherapy is an extension of molecular imaging which utilizes radiopharmaceuticals for treatment of cancer. In this area, we are exploiting the nanometer-range Auger electrons emitted by 111In to cause single-cell killing of tumour cells while avoiding toxicity to normal cells. We are developing novel radiotherapeutics directed towards EGFR, HER2 and EGFR overexpressed on breast cancer cells for treatment of metastatic disease. We are also exploring the treatment of acute myelogenous leukemia (AML) using radiolabeled antibodies directed against CD33 or CD123 epitopes. CD123 is particularly attractive because it is uniquely expressed on leukemic stem cells (LSCs), which are thought to be responsible for recurrence of the disease. In addition, we are developing gold nanoparticles targeted to HER2 which could be used to dramatically radiosensitize breast cancer cells to X-radiation treatment to improve the treatment of locally-advanced breast cancer (LABC). Finally, we are examining combining vaccinia cytolytic virus therapy with targeted radiotherapy for the treatment of peritoneal carcinomatosis. One radiotherapeutic agent (111In-DTPA-hEGF) discovered in our laboratory has been tested in a Phase I clinical trial for treatment of metastatic breast cancer. An extension of this trial at the University of Oxford is being supported by Cancer Research – UK and is expected to commence in 2010.
Graduate students and post-doctoral fellows have opportunities to receive training in radiopharmaceutical design and development, preclinical evaluation as well as clinical investigation in early Phase I/II trials and our laboratory is an active participant in two CIHR-funded traing programs (Excellence in Radiation Research for the 21st Century and Strategic Training Program in Biological Therapeutics).