Cancerous tumors, surrounding cells illuminated by new imaging agent

March 10, 2020

Scientists at Washington University School of Medicine in St. Louis have developed a new imaging agent that could let doctors identify not only multiple types of tumors but the surrounding normal cells that the cancer takes over and uses as a shield to protect itself from attempts to destroy it.

The study appears March 9 in the journal Nature Biomedical Engineering.

The imaging agent, referred to as 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.

"This unique imaging agent identifies cancer cells as well as other compromised cells surrounding the tumor," said Samuel Achilefu, PhD, the Michel M. Ter-Pogossian Professor of Radiology. "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."

The compound binds to the activated form of a protein called annexin A2, which is present in many types of solid tumors but not healthy tissue. The activated form of the protein promotes inflammation and invasiveness of these tumors, which allows the cancer to spread.

Solid tumors that contain activated annexin A2 are found in breast, colon, liver, pancreatic, head and neck, and brain cancers. Since the activated form of the protein also is present in the cells that surround the tumor -- and not normal, healthy cells -- doctors potentially could use this 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. Such co-opted cells also conceal cancer stem cells, whose stealth presence can lead to a recurrence of the tumor.

"We are coming to the realization that to eradicate cancer, we also need to focus on the microenvironment of the tumor," said Achilefu, who also directs the university's Optical Radiology Lab at the Mallinckrodt Institute of Radiology and is co-leader of the Oncologic Imaging Program at Siteman. "Most cancer drugs are designed to target cancer cells. But cancer cells create their own fiefdom, where they impose their own rules. If a normal cell nearby wants to continue living, it must follow the new rules. And slowly these cells come to identify with the tumor rather than their normal identity."

Achilefu expects that with a tumor and its surrounding fiefdom illuminated by the new imaging agent, doctors would have a better chance of removing the entire tumor as well as any areas that are likely to harbor microscopic cancer cells. In past work, Achilefu's team has developed cancer goggles that allow surgeons to visualize cancer cells in real time during surgery to remove a tumor. The new imaging agent can be used with these goggles, which are being evaluated in clinical trials. The researchers also are working on a version of the compound that could be used in positron emission tomography (PET) scans, which many cancer patients undergo to assess whether cancer has spread.

As Achilefu and his colleagues saw that the compound lit up the hijacked cells on the periphery of the tumor, they were surprised to see the imaging agent light up parts of the central core of the tumor as well.

"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."

With this in mind, Achilefu's team conducted mouse studies to show that the researchers can 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," he said. "If the clinical trials are successful with the imaging, we will move into therapy."
-end-
This study was supported by the National Cancer Institute (NCI), grant number R01 CA171651; the National Institutes of Health (NIH), grant numbers U54 CA199092, R01 EB021048, P50 CA094056, P30 CA091842, S10 OD016237, S10 RR031625, and S10 OD020129; the Department of Defense Breast Cancer Research Program, grant number W81XWH-16-1-0286; and the Alvin J. Siteman Cancer Research Fund, grant number 11-FY16-01. Further support was provided by the Alvin J. Siteman Cancer Center at Washington University School of Medicine and Barnes-Jewish Hospital in St. Louis, and the Institute of Clinical and Translational Sciences at Washington University, through the use of the Tissue Procurement Core, which provided tissues of human breast cancer patients. Siteman is supported in part by an NCI Cancer Center Support Grant, grant number P30 CA091842; and the ICTS is funded by the National Institutes of Health's NCATS Clinical and Translational Science Award program, grant number UL1 TR002345. Gabriel Birrane, PhD, provided purified ANXA2 and pANXA2 protein reagents used in the initial study.

Achilefu is a co-inventor on a U.S. patent issued to Washington University covering LS301. The patent may become the subject of a licensing agreement in the future.

Shen D, Xu B, Liang K, Tang R, Sudlow GP, Egbulefu C, Guo K, Som A, Gilson R, Maji D, Mondal S, Habimana-Griffin L, Akers W, Li S, Liu Y, Bloch S, Kurkure S, Nussinov Z, Seidel A, Tsen SD, Achilefu S. Selective imaging of solid tumours via the calcium-dependent high-affinity binding of a cyclic octapeptide to phosphorylated Annexin A2. Nature Biomedical Engineering. March 9, 2020.

Washington University School of Medicine's 1,500 faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is a leader in medical research, teaching and patient care, ranking among the top 10 medical schools in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.