Precision cancer care focuses on identifying the specific biomarkers
of a patient's cancer, which can help doctors make decisions about the
best treatment options. A traditional way to learn about the genetic
makeup of cancer is through a biopsy - in which doctors have to
physically remove tissue from a patient and then examine it.
molecular imaging, which can be used to complement the biopsy and is
noninvasive, can provide added benefit in certain cases, especially when
multiple examinations are needed.
‘New molecular imaging technologies can make it easier to diagnose, monitor, and treat cancers while saving patients from undergoing therapies that could be ineffective and play a role in minimizing side effects.’
New molecular imaging technologies can make it easier to diagnose,
monitor, and treat cancers while potentially saving patients from
undergoing therapies that are likely to be ineffective and playing a
role in minimizing side effects, according to experts from the Abramson
Cancer Center and the Perelman School of Medicine at the University of
In a review published online today in JAMA Oncology
, the Penn team says finding a way to use these techniques more widely in clinical settings should be a top priority.There are four main areas where molecular imaging can have a major
impact, according to the study's lead author David A. Mankoff, the Gerd Muehllehner Professor of Radiology and director of the PET
Center at the Perelman School of Medicine at the University of
Pennsylvania. First, it can help identify patients most likely to
benefit from targeted therapy.
"Once we start treatment, it can also help us plan radiotherapy
treatment and help define the boundaries of the active tumor," Mankoff
Second, it can monitor the movement of drugs throughout the body to
guide drug dosing and minimize side effects. Similarly, it can also
monitor whether those drugs are having an effect. Finally, all of this
data can be combined to predict patient outcomes including overall
Unlike X-ray and ordinary magnetic resonance imaging (MRI), which
reveal the large-scale structures of tissues in the body, molecular
imaging uses special imaging "probe" compounds - injected into the
patient - to highlight a desired molecular target in a tissue of
FDG-PET, one of the only molecular imaging techniques
routinely used in oncology, employs a glucose-like probe, FDG, with a
radioactive isotope of fluorine attached as a beacon. Once it is
injected into the bloodstream, the FDG probe quickly accumulates in
tumors, which tend to make heavy use of glucose. Thus, it "lights up"
those tumors on a PET (positron emission tomography) scan.
FDG-PET, a method that the University of Pennsylvania helped pioneer,
has been used for more than two decades to detect tumors and determine
the extent to which cancer has spread. But the newer PET probes now in
development and testing are meant for many other applications in cancer
Two new classes of probe that show particular promise are designed to
bind to estrogen and HER2 receptors. Breast, uterine, and ovarian
tumors often use these receptors to boost their growth, and many cancer
drugs target them. Detecting the presence of tumor estrogen or HER2
receptors with PET scans would enable oncologists to examine all sites
of cancer for each patient, choose the appropriate drug treatment more
quickly, monitor the tumor for changes that would necessitate a switch
to another treatment, and even evaluate how well a drug is hitting its
Imaging with the new PET probes also could reveal receptors or other
tumor-related markers at sites where the cancer may have spread,
including bone, which is much harder to biopsy.
The probes targeted to breast cancer have shown great promise so far
in breast cancer clinical trials, and Mankoff and his Penn Medicine
colleagues have helped lead this research effort. One national,
multi-center trial focused on the estrogen receptor is co-chaired by
oncologist Amy Clark, a co-author of the review and an
assistant professor of medicine at the Abramson Cancer Center at the
University of Pennsylvania. Another smaller trial of estrogen receptor
imaging is underway at the Abramson Cancer Center's 2-PREVENT
Translational Center of Excellence.
"Many of these methods are already being studied in clinical trials,
but the path from clinical trials to routine clinical use is seldom
easy," Mankoff said. "And molecular imaging methods face some
particularly challenging hurdles such as the need to deliver the
short-lived imaging probes to centers performing the imaging."
Because these methods are so new to oncologists, there is no standard
procedure for testing them, or for making an empirical case for their
clinical value to the FDA, medical insurers, and ultimately oncologists
themselves. "We don't have a good framework yet for moving these
potentially powerful diagnostic tools into routine clinical use,"
Mankoff said. "Among other things, we need to bring the imaging and
oncology communities together to find the best way forward."
Mankoff and his colleagues argue that making a strong clinical case
for these new imaging techniques will mean demonstrating their ability
to improve traditional treatment outcomes such as progression-free
survival and quality of life. Clinical trials of these methods also
could take into account the value of avoiding ineffective treatments. In
one recent trial, researchers showed that a combination of FDG and
HER2-targeted PET imaging was 100 percent accurate in predicting patient
responses to a costly new anti-HER2 breast cancer drug.
"In that case, molecular imaging could have directed treatment to
patients highly likely to benefit and spared many other patients the
toxic effects and costs of ineffective therapy," Mankoff said.
Above all, Mankoff says testing of new imaging methods should focus
on applications where they clearly represent an advance for patients
over other imaging or biopsy-based techniques.
"These clinical trial results for the new molecular imaging methods
are going to be compelling for patients and their referring oncologists
only when they address clinical challenges not met by existing
approaches," he said.
Michael D. Farwell, an assistant professor of Radiology at Penn,
and Daniel A. Pryma, associate professor of Radiology at Penn, also
co-authored the review.