Project 460171

Cancer is a deadly disease and the leading cause of death worldwide. As early detection and treatment can greatly improve patient outcomes, better diagnostic and therapeutic agents are urgently needed. One method physicians used to diagnose cancers is by giving patients an imaging scan called positron emission tomography. Patients receive a small dose of a radioactive agent, which selectively accumulates into tumors and sends a signal to a detector to pinpoint their location. These imaging agents, also called tracers, can be easily modified to carry a more potent radioactive element to kill cancer cells for therapeutic applications. Our goal is to develop radioactive agents to target a protein called gastrin-releasing peptide receptor (GRPR), which is observed in high abundance in many cancer types including prostate and breast cancer. While imaging and therapeutic agents targeting GRPR have been developed, these existing agents are encumbered by severe limitations. Current GRPR-targeting agents get degraded quickly once injected into the body and have much higher accumulation in the pancreas than in tumor tissues. These lead to suboptimal detection for imaging and unwanted toxicity for therapeutic application. Recently, we identified novel GRPR-targeting agents with high tumor uptake and minimal accumulation in the pancreas. For this proposed project, we will modify the chemical structures of GRPR-targeting agents, so they will not get degraded quickly in the body. 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 GRPR in cancer cells. We will evaluate our GRPR-targeting radioactive agents for detection and therapy using mice bearing implanted human prostate and breast tumors. The success of this project will greatly enhance tumor uptake of GRPR-targeting radioactive agents, leading to improved detection sensitivity and treatment efficacy.