Objective The major causes of death in the Western world are cardiovascular diseases and cancer. More accurate detection of these diseases will improve clinical outcomes. Thus, we will develop unique X-ray contrast reagents for use in spectral computerized tomography (CT) that bind active proteases to reveal the exact location and stage of cancer and atherosclerosis.Activity-based probes (ABPs) are small molecules that covalently bind to active proteases. Based on our success in developing optical ABPs for non-invasive optical detection of cancer and atherosclerosis, we will focus on two novel types of reagents: (1) ABPs conjugated to the various contrast elements that can be visualized by x-rays. (2) “smart probes” conjugated to different contrast reagents on each side of the molecule to overcome clearance limitations. Protease found in diseased tissue will selectively bind and remove a part of the molecule, changing the physical properties of the bound probe. Thus, different signals from bound and unbound probes could be detected by photon counting spectral CT scanners.Our initial target, cysteine cathepsin proteases, are overexpressed and activated in cancer and arthrosclerosis. The level of active cathepsins correlates with progression of both diseases, thereby serving as a promising biomarker for these pathologies. The “smart probes” are an innovative type of spectral CT agent that will enable high-resolution rapid imaging in humans before probe clearance.Our probes increase imaging sensitivity since the contrast element remains at the desired site. Moreover, the levels of active cathepsins will reveal critical information regarding disease progression, yielding more accurate diagnoses and improved personalized treatment. For example, these reagents can distinguish between a vulnerable and stable atherosclerotic plaque. Thus, our novel probes will directly reduce cancer and cardiovascular disease mortality by enabling earlier and more accurate disease detection. Fields of science social sciencessociologydemographymortalitymedical and health sciencesclinical medicinecardiologycardiovascular diseasesarteriosclerosismedical and health sciencesclinical medicineoncologymedical and health sciencesbasic medicinepathologynatural sciencesphysical sciencestheoretical physicsparticle physicsphotons Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS7 - Applied life sciences, biotechnology and bioengineering: agricultural, animal, fishery, forestry/food sciences; biotechnology, chemical biology, genetic engineering, synthetic biology, industrial biosciences; environmental biotechnology. Call for proposal ERC-2013-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution THE HEBREW UNIVERSITY OF JERUSALEM EU contribution € 1 499 780,00 Address EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Israel See on map Activity type Higher or Secondary Education Establishments Principal investigator Galia Blum (Dr.) Administrative Contact Hani Ben Yehuda (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE HEBREW UNIVERSITY OF JERUSALEM Israel EU contribution € 1 499 780,00 Address EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem See on map Activity type Higher or Secondary Education Establishments Principal investigator Galia Blum (Dr.) Administrative Contact Hani Ben Yehuda (Ms.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data