Grant: Collaborative Health Research Projects (NSERC partnered)

Glioblastoma multiforme (GBM) (WHO grade IV) is a highly aggressive tumour with distinct histopathological features including high proliferation, necrosis, and considerable neo-vascularization. GBM remains one of the most devastating cancers and is among the most common solid tumours in children. Radiographic and histological evidence have determined that increased tumour vascularity is correlated with the clinical grade of gliomas. At present, tissue samples are required for absolute classification, from which the outcome may be predicted and adjuvant therapies, such as radio and/or chemotherapy, may be determined. Therefore, there is an unmet clinical need to develop a non-invasive method to assess the degree of glioma vascularity and determine the associated clinical aggressiveness. Such a molecular imaging method could significantly improve the clinical management of gliomas. The application of molecular imaging to CNS neoplasms would ensure more accurate diagnosis if an appropriate targeted contrast agent were developed. Previously in our laboratory, the insulin-like growth factor-binding protein-7 (IGFBP7) has been discovered to be a highly up-regulated biomarker specific for GBM vessels and a single domain antibody (sdAbs) that target against IGFBP7 has been developed. Bioconjugation of sdAbs to magnetic resonance (MR) and near-infrared (NIR) imaging contrast agents is a novel method that has the potential to provide accurate molecular imaging of GBM vessels in the clinic. MRI is an advanced 3D non-invasive imaging modality, but the lack of molecular MR imaging contrast agents with sufficient specificity and high relaxivity, and thus MR contrast sensitivity, is a major impediment. We propose to make antibody-nanoparticle conjugates, more specifically to make MR molecular imaging agents consisting of anti-IGFBP7 sdAb targeted FeCo nanoparticles, which are predicted to have a 3 times stronger magnetic moment than 20 nm SPIO (superparamagnetic iron oxide) thus providing better targeted tissue contrast. In addition, it has a turn-on near-infrared optical probe.