18F-FDOPA PET TO ACCESS RESPONSE OF HIGH GRADE GLIOMAS

June 28, 2012 (Miami Beach, Florida) — Metabolic tumor volume assessed by 18F fluoro-phenylalanine positron emission tomography (18F-FDOPA PET) shows treatment response to antiangiogenic therapy as early as 2 weeks after initiation of treatment in patients with recurrent high-grade gliomas, according to new research presented here at the SNM 2012 Annual Meeting.

"From a clinical point of view, being able to tell if a treatment is working is very good for patients because not only are these treatments toxic, they are also extremely expensive," senior author Wei Chen, MD, PhD, associate clinical professor of molecular and medical pharmacology for the Ahmanson Biological Imaging Center at the University of California at Los Angeles David Geffen School of Medicine, told Medscape Medical News.

"It's better to know as early as possible, so patients can avoid unnecessary toxicity and maybe switch to something that works or is less toxic," Dr. Chen said.

Early prediction of response is also of benefit from a research point of view, she added. "When researchers are looking for new agents and treatment methods, they really want a test that is reliable and is a good way to measure lesion response, so this type of imaging is a boon in that regard."

Dr. Chen and colleagues tested combining PET with 18F-FDOPA, an amino acid imaging probe targeting the increased protein transport of glioma cells, to evaluate the ability of the combination to monitor treatment and also assess its use as a staging and restaging tool.

Their study included 30 patients with recurrent high-grade gliomas. The 18F-FDOPA PET scans were done immediately before the start of bevacizumab combination therapy and at 2 and 6 weeks after.

Metabolic tumor volumes using standardized uptake value thresholds were obtained and the response to treatment as assessed with magnetic resonance imaging (MRI) was obtained at 6 weeks.

The predictive power of 18F-FDOPA PET and MRI response were compared with regard to progression-free survival and overall survival.

The study found that 18F-FDOPA PET standardized uptake values and changes during therapy were not predictive of treatment response. However, metabolic tumor volume, metabolic tumor volume changes, and tumor burden were highly prognostic.

At 2 weeks, 18F-FDOPA PET metabolic tumor volume was the most significant predictor for overall survival (P = .001) and progression-free survival (P =.002).

The 17 patients who were metabolic responders survived 3.5 times longer (12.1 months vs 3.5 months; P < .001) than 11 nonresponders. In comparison, 9 responders (based on MRI results) lived 1.4 times as long (12.9 months vs 9.0 months; P =.05) as 20 nonresponders (based on MRI findings).

There were 9 cases with discrepant findings on PET and MRI. In 8 of the 9 cases, 18F-FDOPA PET was able to show treatment response earlier than MRI, Dr. Chen said.

"We need a larger patient population, but still, doctors can now tell their patients that there is a way we can tell if treatment is going to be effective sooner, and ask them if they would like to be part of those studies," Dr. Chen said.

She added that the scan is now the most commonly ordered brain scan at her hospital for patients with brain tumors.

"The agent is approved for clinical use. It is not a new tracer, it's just being used for a different purpose, and still needs FDA approval for this clinical use, but we are using it now, and the approval is in the works. If this were made readily available, it would provide clinicians with a powerful tool to help patients with this deadly disease," she said.

An Important Development

"Using a PET tracer with an analog of an essential amino acid of the brain to get as early indication as possible for the response to treatment is important," Norman LaFrance, MD, an independent consultant from Leesburg, Virginia, told Medscape Medical News.

"Historically, this was a death sentence, but increasingly there are novel treatments coming along that have the potential to be more potent and targeted therapies which will clearly improve patients' survival rates," Dr. LaFrance said.

"Many of these therapies will go on for weeks or months, and they have lots of side effects, so if you have a noninvasive and basically risk-free way [to assess treatment response], which is what this PET scan is, that would be huge. If the treatment is effective, even with some toxicity, and if the patient can continue, then it's worth the risk. If you're not getting anywhere, you can go on to another novel therapy or else move to palliative care and not be subjecting the patient to needless treatment that is making him sick and adversely affecting his quality of life," he said.

The study was supported by the National Cancer Institute at the National Institutes of Health and the US Department of Energy. Dr. Chen and Dr. LaFrance have disclosed no relevant financial relationships.

SNM 2012 Annual Meeting: Abstract 250. Presented June 11, 2012.