Scientists Develop New Scans That Light-Up Aggressive Tumors

Researchers have used a chemical compound to light up treatment-resistant cancers on imaging scans, in a breakthrough that could help medical professionals better target and treat cancer.

The authors at King’s say that using the radiotracer – an injected compound used in PET scans – could help inform doctors that a patient's aggressive cancer will not respond to chemotherapy before treatment is given. This would prevent the patients receiving unnecessary treatment and provide them with alternative options that will give them the best chance of beating the disease.

The paper, published today in Nature Communications, shows therapy-resistant non-small cell lung cancer tumors "lit up like a Christmas tree" on PET scans when the radiotracer was injected.

Tim Witney, a professor of molecular imaging from King’s College London, and lead researcher of the study said: “Currently, there is no quick and early method that shows whether malignant tumors are resistant to treatment. Time is essential for patients with lung cancer, and many cannot afford to wait to see if chemotherapy is working. 

Non-small cell lung cancer is the most common type of lung cancer in the UK and 47,000 people are diagnosed with it every year. Standard care includes surgery, radiotherapy, chemotherapy and immunotherapy, but despite advancements in treatment, survival rates have not improved much in the past decade.

Typically, patients with lung cancer will be started on a treatment plan – such as chemotherapy – and then wait twelve weeks to have a CT or PET scan to see whether the treatment has shrunk the tumor, or the tumor has stayed the same or has grown. But twelve weeks can often be too late to change course of treatment and end-of-life care is frequently the only option.

Researchers from King’s re-purposed a radiotracer, currently used as a diagnostic tool in clinical trials in the USA and South Korea, to show treatment-resistant tumors on PET scans. The molecule targets xCT, a tumor-associated protein which is present on therapy-resistant tumors. In images from the study, PET scans of animal models show tumor-resistant cancer cells light up brighter compared to tumors responsive to treatment.

The authors will now trial this in humans with a phase I clinical trial beginning in January at St Thomas’ Hospital in London. The trial will recruit 35 patients and use the total-body PET scanner at the hospital’s PET Centre to see xCT with imaging before and after patients receive treatment.

Professor Witney added: “Our study is the cumulation of five years of work. Frequently, cancer patients find out too late that the treatment they’re on does not work. The radiotracer ¹⁸F-FSPG binds to the tumor-resistant cells and lights up like a Christmas tree in imaging – clearly showing the aggressive cancer. With this technique, we can give the right treatment to the right patient, making it more cost-efficient for the NHS and providing hope for patients with aggressive tumors.”

In the same paper, researchers also show that xCT can also be targeted by an antibody-drug conjugate, a new class of drug designed as a targeted treatment for therapy-resistant cancer cells, which selectively kills these cells whilst minimizing unwanted toxicity. While research is still in the early stages, the authors hope this could offer a glimmer of hope for patients with the most aggressive and difficult-to-treat cancers, including lung, pancreatic and breast cancers.

Reference: Greenwood HE, Barber AR, Edwards RS, et al. Imaging NRF2 activation in non-small cell lung cancer with positron emission tomography. Nat Commun. 2024. doi: 10.1038/s41467-024-54852-4

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