Study challenges conventional understanding of signal from new diagnostic imaging technique
August 24, 2020
Medically Reviewed | Last reviewed by an MD Anderson Cancer Center medical professional on August 24, 2020
Diagnostic imaging is a powerful tool for clinicians and researchers to see cancer in the body, enabling them to distinguish between benign and malignant areas, find metastases, or see how a tumor is responding to treatment. MD Anderson researchers are continually working to advance new imaging technologies, and a new study out this week has important implications for properly understanding and applying a new technique in the clinic.
Certain imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI), are useful in providing anatomical information about the tumor, explains David Piwnica-Worms, M.D., Ph.D., chair of Cancer Systems Imaging. These images are frequently used to determine disease stages and response to treatment.
On the other hand, he says, techniques such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) can provide important molecular information about the tumor, such as metabolic activity. This can be valuable in finding any small areas of cancer metastases or distinguishing between normal and malignant tissue.
A new technique, which uses MRS, offers potential advantages over the well-known PET scan, but a study led by Piwnica-Worms’ team has found that the traditional interpretation of signals from that technique are not correct. The findings, published today in the Proceedings of the National Academy of Science, are critical for ensuring that this technique can be appropriately used as a diagnostic imaging tool.
Imaging to better understand a cancer’s increased metabolism
Increased metabolic activity is a hallmark of cancer. Converting lots of sugars to cellular building blocks and energy through a process known as glycolysis helps to fuel a cancer’s uncontrolled growth. A PET scan takes advantage of this, using a radiolabeled glucose analog (flurodeoxyglucose; FDG), which has small amounts of radioactivity (F-18), to make tumors “light up” so that they’re visible on a scan.
“Normal cells process glucose in the same way, but cancer cells do it in rip-roaring high levels,” says Piwnica-Worms. “So, compared to the background normal tissue, a tumor or metastasis in the body will look really bright on a PET scan because of this trace amount of radioactivity trapped there.”
Using MRS imaging has the potential to also highlight increased metabolic activity, but it does so without using a radioactive compound. Instead, it is able to detect special magnetic properties of chemical compounds to visualize activity in our cells.
MRS typically is not as sensitive as PET imaging, but recently the use of hyperpolarized compounds, which have a very high magnetic state, has increased the signal by more than 10,000 fold, says Piwnica-Worms. That allows for the study of metabolic reactions in ways that weren’t possible before.
By using a hyperpolarized form of a sugar metabolite known as pyruvate with a special form of carbon (C-13), MRS is able to follow the chemical conversions of pyruvate by glycolysis and visualize metabolic activity in the body.
While the small amounts of radioactivity from PET are not dangerous, this MRS technique offers an option with no radioactivity as well as an opportunity to get more detailed information about metabolism in the body, explains Piwnica-Worms.
Challenging traditional thinking about what the signal means
As the use of hyperpolarized C-13 pyruvate MRS has advanced toward the clinic, conventional thinking was that the technique would be applied similar to F-18 FDG PET imaging: areas with high metabolic activity would light up with increased signals. Thus, a higher signal would indicate a more active or aggressive cancer.
However, until now the studies hadn’t been done to verify that was indeed the case.
“Our science has challenged the conventional orthodoxy about what the signal actually means,” says Piwnica-Worms. “We propose that our work changes the meaning of that signature, and that’s important as we are beginning to apply this in human medicine.”
Through the work of a multidisciplinary, collaborative research team, Yi Rao, a graduate student in the Piwnica-Worms group and lead author, was able to clarify that increased signals from this approach do not necessarily reflect high levels of metabolic activity, but instead high levels of the pyruvate being taken into the cell.
Pyruvate must be transported into the cell by a protein in the cell membrane called MCT1. Through their work, the researchers showed that the levels of MCT1 transporter in cancer cells are a bottleneck, or rate-limiting step, for this metabolic process to be detected. Thus, a high signal from this MRS technique does not indicate a more aggressive tumor, but rather a tumor with more of the MCT1 protein.
Knowing this, it became clear that by using the conventional interpretation of this technique, there was a potential for error, that is, false negatives, meaning an aggressive tumor that was considered to be benign because of a low signal.
“We showed explicitly that you could have an aggressive tumor, in this case a metastatic breast cancer model that has high metabolic activity, and we saw no signature from MRS because it has very low amounts of the MCT1 transporter,” says Piwnica-Worms.
Implications for diagnostic imaging
While it does challenge the conventional thinking, this study does not show that the technique was flawed or not working, says Piwnica-Worms. “It just means that we need to reinterpret our data in the context of using this technique for cancer diagnostic imaging.”
There are good data available on which cancer types have high or low levels of MCT1, so hyperpolarized MRS may be useful when combined with those data. That is something that needs to be tested further. It will be the focus of future work for Piwnica-Worms’ team.
This research was supported by the National Institutes of Health, the Gerald Dewey Dodd Jr. Endowed Distinguished Chair, a UT STARs Award, the Pancreatic Cancer Action Network, the Cancer Prevention and Research Institute of Texas, and the Barbara Cox Anthony/Koch Foundation. For a complete list of funding support and collaborating authors, please see the full paper.
Refer a patient to MD Anderson online or by calling 1-877-632-6789.
Diagnostic imaging is a powerful tool for clinicians and researchers to see cancer in the body, enabling them to distinguish between benign and malignant areas, find metastases, or see how a tumor is responding to treatment. MD Anderson researchers are continually working to advance new imaging technologies, and a new study out this week has important implications for properly understanding and applying a new technique in the clinic.
Certain imaging techniques, such as computed tomography (CT) or magnetic resonance imaging (MRI), are useful in providing anatomical information about the tumor, explains David Piwnica-Worms, M.D., Ph.D., chair of Cancer Systems Imaging. These images are frequently used to determine disease stages and response to treatment.
On the other hand, he says, techniques such as positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) can provide important molecular information about the tumor, such as metabolic activity. This can be valuable in finding any small areas of cancer metastases or distinguishing between normal and malignant tissue.
A new technique, which uses MRS, offers potential advantages over the well-known PET scan, but a study led by Piwnica-Worms’ team has found that the traditional interpretation of signals from that technique are not correct. The findings[NR1] , published today in the Proceedings of the National Academy of Science, are critical for ensuring that this technique can be appropriately used as a diagnostic imaging tool.
Imaging to better understand a cancer’s increased metabolism
Increased metabolic activity is a hallmark of cancer. Converting lots of sugars to cellular building blocks and energy through a process known as glycolysis helps to fuel a cancer’s uncontrolled growth. A PET scan takes advantage of this, using a radiolabeled glucose analog (flurodeoxyglucose; FDG), which has small amounts of radioactivity (F-18), to make tumors “light up” so that they’re visible on a scan.
“Normal cells process glucose in the same way, but cancer cells do it in rip-roaring high levels,” says Piwnica-Worms. “So, compared to the background normal tissue, a tumor or metastasis in the body will look really bright on a PET scan because of this trace amount of radioactivity trapped there.”
Using MRS imaging has the potential to also highlight increased metabolic activity, but it does so without using a radioactive compound. Instead, it is able to detect special magnetic properties of chemical compounds to visualize activity in our cells.
MRS typically is not as sensitive as PET imaging, but recently the use of hyperpolarized compounds, which have a very high magnetic state, has increased the signal by more than 10,000 fold, says Piwnica-Worms. That allows for the study of metabolic reactions in ways that weren’t possible before.
By using a hyperpolarized form of a sugar metabolite known as pyruvate with a special form of carbon (C-13), MRS is able to follow the chemical conversions of pyruvate by glycolysis and visualize metabolic activity in the body.
While the small amounts of radioactivity from PET are not dangerous, this MRS technique offers an option with no radioactivity as well as an opportunity to get more detailed information about metabolism in the body, explains Piwnica-Worms.
Challenging traditional thinking about what the signal means
As the use of hyperpolarized C-13 pyruvate MRS has advanced toward the clinic, conventional thinking was that the technique would be applied similar to F-18 FDG PET imaging: areas with high metabolic activity would light up with increased signals. Thus, a higher signal would indicate a more active or aggressive cancer.
However, until now the studies hadn’t been done to verify that was indeed the case.
“Our science has challenged the conventional orthodoxy about what the signal actually means,” says Piwnica-Worms. “We propose that our work changes the meaning of that signature, and that’s important as we are beginning to apply this in human medicine.”
Through the work of a multidisciplinary, collaborative research team, Piwnica-Worms was able to clarify that increased signals from this approach do not necessarily reflect high levels of metabolic activity, but instead high levels of the pyruvate being taken into the cell.
Pyruvate must be transported into the cell by a protein in the cell membrane called MCT1. Through their work, the researchers showed that the levels of MCT1 transporter in cancer cells are a bottleneck, or rate-limiting step, for this metabolic process to be detected. Thus, a high signal from this MRS technique does not indicate a more aggressive tumor, but rather a tumor with more of the MCT1 protein.
Knowing this, it became clear that by using the conventional interpretation of this technique, there was a potential for error, that is, false negatives, meaning an aggressive tumor that was considered to be benign because of a low signal.
“We showed explicitly that you could have an aggressive tumor, in this case a metastatic breast cancer model that has high metabolic activity, and we saw no signature from MRS because it has very low amounts of the MCT1 transporter,” says Piwnica-Worms.
Implications for diagnostic imaging
While it does challenge the conventional thinking, this study does not show that the technique was flawed or not working, says Piwnica-Worms.
“It just means that we need to reinterpret our data in the context of using this technique for cancer diagnostic imaging.”
There are good data available on which cancer types have high or low levels of MCT1, so hyperpolarized MRS may be useful when combined with those data. That is something that needs to be tested further. It will be the focus of future work for Piwnica-Worms’ team.
This research was supported by the National Institutes of Health, the Gerald Dewey Dodd Jr. Endowed Distinguished Chair, a UT STARs Award, the Pancreatic Cancer Action Network, the Cancer Prevention and Research Institute of Texas, and the Barbara Cox Anthony/Koch Foundation. For a complete list of funding support and collaborating authors, please see the full paper here[NR2] .
Refer a patient to MD Anderson online or by calling 1-877-632-6789.
Topics
Breast CancerOur science has challenged the conventional orthodoxy about what the signal actually means.
David Piwnica Worms, M.D., Ph.D.
Physician & Researcher