Duration: June. 2012 - May. 2014
Funding: € 178.803
Project Coordinator: C. Pitris ; Partner: A. Odysseos
This project brings together expertise in medical optics and optoelectronics, magnetics, coordinate Lanthanide chemistry, bio-organic synthesis and molecular oncology, aiming at introducing a break-through solution for the overall management of colorectal cancer and potentially other malignancies expressing the epidermal growth factor family of receptors (EGFR). The solutions is based on prototype metal-based functionalized compounds engaging cutting-edge synthetic and complexation approaches. Initially, a panel of kinetically stable prototype lanthanides complexes with potent (a) optical (e.g near infrared spectroscopic) and (b) magnetic /relaxation properties will be designed and synthesized as building blocks for heterometallic arrays and subsequently the lanthanide complexes will be functionalized to a series of biologically active bimodal theranostic agents with anti-EGFR recognizing and inhibiting properties. Functionalization of the probes with the recognizing and therapeutic ligands (i.e. anilinoquinazolines) will increase the molecular size, thus optimizing proton relaxivity and magnetic efficacy. Diagnostic specificity will be assessed by ERB-B1 recognition and internalization of the compounds on (a) cell monolayers and (b) 3-dimensional tissue phantoms of cell lines differentially expressing ERB-B1 under inverted NIR microscope. Highly sensitive and efficacious compounds will be considered for further development as theranostic agents for early detection and therapy of CRC in subsequent pre-clinical models with the application of multimodal Molecular Imaging. This approach enables the quantitative imaging of defined cancer biomarkers in a non-invasive manner, aiding in lesion detection, patient stratification, new drug development and validation, dose optimization and treatment monitoring.