Diagnosis and therapy of cancer, inflammatory and thrombotic diseases

Activated platelets have been shown to play an important role in cancer, inflammation and thrombotic diseases. This project would focus on Glycoprotein (GP) IIb/IIIa, which plays an important role in the aggregation of platelets. GPIIb/IIIa is the most abundant platelet receptor; it undergoes a change in confirmation when activated. For this reason, this molecule has been chosen as the target epitope for molecular imaging. The use of small recombinant antibodies for diagnostic molecular imaging and targeted drug delivery are well-established in our lab. We propose to conjugate activated GPIIb/IIIa targeting recombinant antibodies to different contrast agents for their respective imaging modality. These recombinant antibodies can be used for diagnostic imaging as well as targeted delivery of pharmacological treatment. Our group has access to a variety of clinically available imaging modalities, including Magnetic Resonance Imaging (MRI), ultrasound, Computed Tomography (CT) and Positron Emission Tomography (PET), as well as the latest preclinical scanners, such as new 19-Flourine MRI technology and 3D Fluorescence Emission Computed Tomography (FLECT). This project aims to investigate activated platelet-targeted contrast agents for detection of inflammation, cancer and/or thrombosis using molecular imaging, thereby providing better diagnostic technology. By harnessing the targeting ability of the antibodies, we can then conjugate drugs onto them for side-effect-free, targeted drug delivery. Technologies/disease models to learn/apply: cell culture, flow cytometry, molecular biology, PCR, Western blots, animal models and statistical methods.