ICRF Scientist Researching Tools for Early Detection of Pancreatic Cancer

Lucio Frydman, PhD, of the Weizmann Institute of Science, is investigating techniques for understanding, diagnosing and assessing treatment for pancreatic cancer.  

As a renowned expert in magnetic resonance imaging (MRI), can you briefly describe the challenges in early detection of pancreatic cancer?

My work focuses on pancreatic ductal adenocarcinoma (PDAC), a highly aggressive form of pancreatic cancer and a leading cause of cancer-related mortality. It is currently the third most common cause of cancer-related deaths, second only to colon and lung cancer in the U.S. Seven percent of cancer deaths are due to PDAC, and with a five-year survival of 9 percent, it is among the deadliest of cancers. This is largely due to difficulties in its early diagnosis and the dearth of screening tests, compared to lung, colorectal, breast and prostate cancers. In fact, PDAC diagnosis comes too late for most patients, and even with its resection survival is little more than a year.  Imaging methods have been remarkably ineffective in helping to change this state of affairs: CT, endoscopic ultrasound, MRI, and PET, are all used for detecting pancreatic cancer and guiding its needle biopsies – but they have been found lacking despite the period of ten years that it takes for PDAC to develop. PET plays an important role in monitoring for metastases, yet its PDAC sensitivity and specificity is not good – even worse than that of MRI. Compounding this bleak picture is the inability of most methods to distinguish PDAC from non-malignant pancreatitis, an uncertainty that leads to unnecessary biopsies in the best case scenario, and to potentially fatal misdiagnoses and treatments in too many occasions.  

What are you hoping to achieve in your Project Grant research?

Of particular usefulness to stage the status and progression of cancers is the measure and mapping of the Warburg effect – a hallmark of tumors. The Warburg effect is a metabolism-related process whereby, when fed with glucose, tumors will generate a compound called lactate, instead of leading to the more efficient conversion of glucose into CO2 and water. Diagnosis methods like PET excel mapping the Warburg effect, thereby being of paramount importance in clinical practice.  PET does not detect the conversion of glucose into lactate however, but rather an increase in glucose uptake; in the “eating” of a radioactive derivative of glucose by cancerous cells.

Stimulated by PET’s success, the present ICRF grant seeks to develop an alternative way of detecting altered metabolic processes – not by injecting radioactive glucose and seeing its uptake, but by administration of deuterated (2H) chemicals, particularly deuterated glucose. Preliminary studies that we have carried out indicate that MRI of 2H could become a key tool for detecting glucose’s transformation into lactate, providing a rich metabolic information. Pancreatic cancer is one of the deadliest forms of cancer in both the U.S. and Israel and is expected to become the second deadliest cancer by the 2030s –unless stopped by advances in its early diagnosis. Our ultimate goal is creating a new tool for understanding, diagnosing, assessing treatment, and eventually screening high-risk populations, that will be reliable, uncompromised by ionizing radiation, and translatable to clinical facilities worldwide.

How has ICRF helped further your study and diagnosis of pancreatic cancer?

ICRF has allowed us to achieve to milestones. In one of them, it enabled us to carry out 2H MRI experiments on animals implanted with several pancreatic cancer models. In all of them we have seen that deuterated glucose transformed, solely in the tumors, into deuterated lactate; other pathways also highlighted the malignancies through the enhanced generation of deuterated water. This means we can detect the presence of tumors that are otherwise not visible in conventional 1H MRI. In parallel, we have used our physics background to develop improved 2H MRI methods that can deliver the individual signatures of these metabolites – glucose, water, lactate – non-invasively, and image their in vivo distributions with sensitivities and spatial resolutions that are remarkably better than those arising from traditional MRI options. The goal of our ICRF-funded research is to further these tools, use them to better understand the biology of pancreatic cancer, optimize them to diagnose these cancers on animals, and eventually translate these minimally invasive techniques on humans –including the staging the disease and differentiation from confounding maladies such as pancreatitis. Eventually, we also hope to use these techniques to diagnose the status of established and emerging PDAC treatments, as viewed by their effects on metabolic processes.

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