First-in-Human Trial of 4-18F-(2S,4R)-Fluoroglutamine Positron Emission Tomography

Lay Summary

A PET imaging tracer may accelerate brain tumor treatment progress

A 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 participating patients.

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.

Significance: 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 therapies.