Pancreatic cancer is notorious for its late detection and high mortality rate, but a new Israeli approach to magnetic resonance imaging (MRI) that illuminates pancreatic tumours offers hope for earlier diagnoses and treatment.
The challenge of detecting pancreatic cancer arises from the pancreas’s deep location in the abdominal cavity, which varies among individuals, often concealing tumours until it is too late for effective treatment.
Although it is only the 12th most common form of cancer globally, pancreatic cancer was the sixth deadliest in 2020. Without improved detection, pancreatic cancer is projected to become the deadliest form of cancer by 2030.
However, an innovative MRI method developed by the Weizmann Institute of Science tracks how cells metabolize glucose, similar to how glucose tolerance tests indicate diabetes. The findings were recently published in the peer-reviewed Science Advances journal.
Nearly a century ago, Nobel Prize laureate Otto Warburg discovered that cancer cells consume glucose at unusually high rates compared to non-cancerous cells, a phenomenon now known as the Warburg effect.
This effect causes glucose to ferment into lactate rather than being fully metabolized into carbon dioxide. Leveraging this metabolic quirk, the Weizmann MRI method maps specific metabolic products unique to cancer cells, potentially allowing for the identification of pancreatic cancer.
The researchers, led by Prof. Lucio Frydman and Prof. Avigdor Scherz, utilized chemically altered glucose containing a stable isotope of hydrogen called deuterium. This modified glucose was injected into mice with pancreatic tumours before scanning.
According to Frydman, this new method may surpass traditional MRI and positron emission tomography (PET) scans, both of which struggle to accurately identify pancreatic tumours.
“Traditional MRI fails to detect pancreatic tumours because, even when external contrast agents are added, the scanning is not specific enough to highlight the presence and location of the cancer. Doctors can’t see the tumour until the patient feels its effects,” Frydman said.
“Even when the scan indicates an abnormality, it often cannot be distinguished from an inflammation or a benign cyst. Likewise, PET scans cannot necessarily be trusted because a positive scan does not always mean the patient has cancer, and a negative PET scan does not always mean the patient is cancer-free,” he explained.
Standard preventive care for pancreatic cancer currently involves periodic CT and MRI scans, often accompanied by invasive and uncomfortable endoscopic biopsies, but this combined approach rarely works. The researchers aimed to address this diagnostic gap by using MRI to detect the distinct metabolic patterns of normal and cancerous tissues.
“In healthy cells, glucose digestion ends with carbon dioxide, which we exhale,” Frydman explained. “Cancer cells, however, stop this process early, producing lactate, which aids in their proliferation.”
The challenge lay in detecting the small amounts of lactate produced by cancer cells. Conventional MRI measures abundant protons in tissue water, overshadowing the faint lactate signal. To solve this, the researchers replaced glucose’s protons with deuterium. This “deuterized” glucose, when metabolized by cancer cells, produced detectable deuterized lactate, overcoming the water signal interference.
Enhancing the sensitivity of this method, Frydman’s team developed advanced experimental and image-processing techniques, significantly improving the detection of deuterized lactate. The new MRI scans illuminated even the smallest tumors, while healthy tissues remained dark.
“Even if the cancer is not caught in time, deuterium MRI will help measure rates at which the glucose-to-lactate conversion happens. This could provide a crucial metric for predicting the usefulness of certain treatments, or even determining whether a treatment is working. This could establish deuterium MRI as a preferred method for diagnosing hard-to-identify pancreatic tumors and choosing the treatment that will generate the best prognosis,” Frydman said.
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