A PET Imaging Tracer may Accelerate Brain Tumor Treatment Progress
First-in-Human Trial of 4-18F-(2S,4R)-Fluoroglutamine Positron Emission Tomography
Mark Dunphy, D.O.
Memorial Sloan-Kettering Cancer Center0, Department of Radiology
David Mahoney Neuroimaging Program
September 2015, for 3 years
A PET imaging tracer may accelerate brain tumor treatment progress
new non-invasive PET imaging tracer is showing promise for improving the
ability to differentiate indolent brain tumors from those that are aggressively
growing, and for assessing the aggressive tumor’s response to therapy, faster
and more reliably than currently available methods. This study will provide
preliminary validation of this technique by expanding the number of
Standard structural MRI imaging
has been the primary radiologic technique used to determine whether a brain
tumor is a low grade indolent glioma that can be safely monitored or a high
grade aggressive tumor that must be treated immediately. MRI is also the
primary imaging technique used to assess the tumors’ post-treatment responses.
Does residual tumor remain? Does the tumor recur? Does a low grade indolent
tumor transform into a high grade glioma? Unfortunately, though, MRI has a
limited capacity to reveal answers to these critical questions rapidly and
accurately, essential when patients’ lifetimes are measured in months.
MRI’s speed and accuracy are
limited by several key factors. First, certain characteristics of low grade and
high grade gliomas overlap, making it difficult to differentiate the two using
MRI. Second, ironically, if a specific treatment is effective in killing off
the cancerous and surrounding cells, this process results in inflammation and
edema. The swelling produced, though, often mimics tumor growth as seen on MRI.
So physicians typically need to wait for an additional month or two for
follow-up scans to confirm whether the treatment is working or the tumor is
truly progressing and requires a change in treatment.
Now a metabolic PET tracer
(F-18 Fluoroglutamine) may provide a faster and more reliable alternative.
Since tumors rely on exogenous glucose for fuel, the tracer is based on the
premise that tumor cells will take up (consume) the metabolic glutamine tracer
and this will be evident on PET scans. To date, this PET tracer has been tested
in nine glioma patients (four with low grade and five with high grade tumor).
Initial findings show that the PET tracer differentiates aggressive tumors from
indolent ones: Only the high grade gliomas consume an abnormally high amount of
the PET tracer. Moreover, inflammation does not take up the tracer. So,
treatments that produce inflammation by killing cancer cells can be
differentiated from actual tumor progression and spread.
The investigators hypothesize,
therefore, that the PET tracer will provide definitive assessment of treatment
efficacy within one month of treatment initiation compared to two or more
months needed for accurate MRI assessment. They will test this hypothesis in an
additional 18 patients. These patients will undergo MRI and PET scans before
glioma treatment and a month following treatment, when MRI scans are unreliable
in differentiating inflammation from tumor progression. The investigators then
will re-image patients over the following few months with MRI, when its
reliability is greater.
Next, they will compare PET
findings of treatment efficacy at one month to the MRI treatment efficacy
results obtained over several additional months of treatment. If the later MRI
results confirm the earlier PET results, the study will provide validation that
the PET tracer yields rapid definitive results of treatment efficacy.
Physicians then can assess whether to continue with the current treatment or
change to a new one. The investigators also will analyze surgically removed
tumor tissue to study genes and proteins that may reveal why consumption of the
PET tracer differs among low grade tumors, and whether relatively higher
consumption by some compared to others is a biomarker indicating imminent
conversion from low to high grade glioma.
: If validated, this PET tracer will enable
clinicians to rapidly differentiate low from high grade tumors and assess
treatment efficacy, and will expedite clinical testing of experimental glioma