Grant: Project Grant

Cancer is the leading cause of death in developed countries. More effective diagnostic and therapeutic agents are urgently needed to improve patient outcome. One method doctors use to diagnose cancer is positron emission tomography. Patients receive a small dose of a radioactive agent which accumulates into tumors and sends a signal to a camera to localize tumors. These imaging agents can be modified to carry a more potent radioactive element to kill cancer cells, making them potential radiotherapeutic agents. However, the accumulation of theses radioactive agents in tumors might not be high enough, so some tumors might not be detected or cured using this strategy. The main causes of the low tumor accumulation include (1) the radioactive agents are cleared from the body too quickly so they do not have much chance to bind to their targets (markers) in tumors; and (2) these markers are present only in cancer cells, but not in the non-cancer-cell components of tumors (called tumor stroma) which might make up to 90% of the whole tumor mass. The goal of this proposed project is to develop novel radioactive agents which can bind to markers in cancer cells and also a specific target called fibroblast activation protein (FAP) present in abundance in tumor stroma. In addition, we will also introduce a novel chemical component to these radioactive agents, so they can circulate longer in the body, and have more chances to bind to makers in cancer cells and FAP in tumor stroma. The success of this project will greatly enhance tumor uptake of radioactive agents, leading to improved detection sensitivity and treatment efficacy. In addition, the general strategy developed by this project can be applied to other cancer-marker-binding agents to improve their accumulation in a variety of FAP-expressing tumors, ultimately leading to reduced mortality and improved prognosis for cancer patients in Canada and worldwide.