Final Report Summary - THERAPEUTIC QABP (Protease Quenched Activity-Based Probes for Targeted Cancer Diagnostic and Therapy) The goal of this project was to generate unique fluorescent probes that would enable simultaneous diagnoses and treatment of cancer. These probes target specific active enzymes elevated in inflammation and in cancer tissues. They emit fluorescent light only upon binding the active enzymes therefore the probes were used to detect cancer using non-invasive methods. Furthermore, these probes carry tags that were used to treat these tissues by generating reactive toxic molecules just by shining visible light at them. During the last two years of the project we have used the probes that we have designed and synthesized, they were found to bind their enzyme targets efficiently and specifically. The probes were detected in the cells using fluorescent microscopy and a few were found to induce death of cancerous cells after light treatment. As intended the probes worked very well in vivo, when subjected to tumor bearing mice they accumulated at the tumor site and enabled non-invasive optical detection of the tumor. Most importantly, light treatment of tumors that accumulated the probe after systemic injection, lead to high levels of cells death within the tumor. Thus all goals of this project are completed.The project described here has wide impact; it is the first time that activity-based probes are used as a theranostic agent that enables both detection and treatment of cancer. These probes can also be used for other diseases with elevation of the same enzyme class such as atherosclerosis, and arthritis. The technology developed in this project has critical importance since it can be modified to target other proteases and if has a strong translational aspect.