Scientists at Washington University School of Medicine have developed an imaging agent that can identify multiple types of tumors as well as the surrounding normal cells that the cancer uses as a shield against attempts to destroy it. “This unique imaging agent identifies cancer cells as well as other compromised cells surrounding the tumor,” professor Samuel Achilefu said. “Cancer transforms surrounding cells so that it can proliferate, spread to other parts of the body, and escape treatment. This imaging compound can detect cancer cells and their supporting cast, the diseased cells that are otherwise invisible.” A new imaging agent, developed at Washington University School of Medicine in St. Louis, illuminates cancerous cells of a breast tumor. The new agent lights up cancer cells and the supporting cells that act as a shield and protect the tumor from various treatment strategies. The new investigational agent is being tested in small clinical trials. Courtesy of the Achilefu lab. The researchers showed that in a range of solid tumors, a cyclic octapeptide labeled with a near-infrared dye selectively bound to the activated form of a protein that is present in many types of solid tumors but not in healthy tissue. The activated form of the protein annexin A2 promotes inflammation and invasiveness in tumors, which allows the cancer to spread. Since the activated form of the protein also is present in the cells that surround the tumor — and is not present in normal, healthy cells — doctors potentially could use the imaging agent to identify cells the tumor has “hijacked.” Despite their benign status, these hijacked cells protect the tumor from chemotherapy, radiation, and other attempts to kill the cancer cells. By illuminating a tumor and its surrounding cells with the new imaging agent, referred to as LS301, doctors would have a better chance of removing the entire tumor as well as any areas that could harbor microscopic cancer cells. As proof-of-concept, the researchers used LS301 to detect tumor xenografts and metastatic lesions and perform fluorescence-guided surgical tumor resection in mice. They found that the compound lit up the hijacked cells on the periphery of the tumor, as well as parts of the central core of the tumor. “We were amazed when we saw this because it’s extremely difficult to access anything inside a tumor,” Achilefu said. “There seems to be a type of immune cell that carries the imaging agent into the core of the tumor. So we now see the tumor margin and the core light up. This allows us to imagine a situation in which we could deliver a drug to the outside and the inside of the tumor at the same time. This dual targeting is not something we purposefully designed — it’s not something we ever anticipated.” In mouse studies, the researchers were able to attach a chemotherapy drug to the compound and use it to image the tumor and treat the disease simultaneously. “Attaching a chemotherapy drug to this targeted imaging agent could reduce side effects as we are delivering the drug directly to the tumor,” Achilefu said. The imaging agent LS301 has been approved for investigational use in small clinical trials at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. The first trial will investigate its use in imaging breast cancer. Achilefu said that if the clinical trials are successful, the imaging agent would be moved into therapy. The research was published in Nature Biomedical Engineering (www.doi.org/10.1038/s41551-020-0528-7).