Researchers at King’s College London have developed a new imaging technique that lights up treatment-resistant cancers at an earlier stage, a breakthrough that could allow doctors to determine which aggressive cancers may not respond to chemotherapy. Using a radiotracer—a chemical compound used in PET scans—the researchers demonstrated that non-small cell lung cancer (NSCLC) tumors resistant to chemotherapy “lit up like a Christmas tree” on imaging scans.
“Currently, there is no quick and early method that shows whether malignant tumors are resistant to treatment,” said Tim Witney, professor of molecular imaging at King’s College London and lead researcher of the study.
The new PET imaging technique, published in Nature Communications, could prevent patients from receiving unnecessary treatments that often have toxic side effects—and instead suggest alternate ways to treat their tumors.
“Time is essential for patients with lung cancer, and many cannot afford to wait to see if chemotherapy is working. We wanted to increase the window of opportunity for treatment for these patients—giving them more choice and a better chance of survival.”
NSCLC is the most common form of lung cancer in the U.S., accounting for approximately 80% to 85 % of the total of 236,000 new cases of lung cancer this year, according to the American Cancer Society. Standard treatments for NSCLC include surgery, chemotherapy, radiotherapy and immunotherapy. After receiving treatment patients then wait about three months for a follow up CT or PET scan to assess if the treatment was effective. But this time lapse can result in some patients discovering that the treatment was not effective, and it is often too late to switch to more effective options, resulting in poor outcomes.
For this research, the King’s College team focused on a molecule called xCT, which is part of a transport system that regulates the exchange of cystine and glutamate between cancer cells and the surrounding environment. Previous research has shown xCT is particularly active in cancers that are resistant to chemotherapy. The investigators repurposed a radiotracer called 18F-FSPG, which is currently used in clinical trials in the U.S. and Korea, to bind to xCT, which allows it to be seen on PET scans. In animal models, the researchers found that treatment resistant cancer cells lit up much brighter than those tumor cells that are responsive to treatment.
“Our study is the cumulation of five years of work,” Whitney said. “Frequently, cancer patients find out too late that the treatment they’re on does not work. With this technique, we can give the right treatment to the right patient.”
Based on these findings, the researchers are planning a Phase I clinical trial, set to begin in January at St Thomas’ Hospital in London. This trial will seek to enroll 35 patients, and will employ the repurposed radiotracer for total-body PET scans to detect xCT both before and after treatment.
In addition to its diagnostic potential, the study also suggests a possible therapeutic approach. The researchers found that the xCT protein could be targeted by an antibody-drug conjugates (ADC). These drugs are designed to specifically target and destroy therapy-resistant tumor cells while minimizing damage to healthy tissue. In animal models, treatment with an xCT-targeting ADC resulted in significant tumor growth suppression and prolonged survival.
