PET Radiotracer Identifies Glioma Treatment Response

A PET imaging protocol using an amino acid analog radiotracer in patients with recurrent high-grade gliomas identified responses to treatment with bevacizumab as early as 2 weeks after starting therapy in a prospective study.

In the 28-patient pilot study, the metabolic tumor volume measured in follow-up PET scans with 6-¹⁸F-fluoro-L-DOPA (¹⁸F-FDOPA) at 2 and 6 weeks after the baseline scan proved to be the most significant predictor of survival with the method.

There is currently no reliable way to predict treatment response noninvasively in patients with malignant glioma, which has only 6% overall survival at 5 years. Chemotherapeutics have toxic side effects and are expensive, "so from the patient’s point of view, if a treatment doesn’t work, it’s important to get that information as early as possible," said the senior investigator of the study, Dr. Wei Chen of the division of molecular and medical pharmacology at the University of California, Los Angeles.

The ability to detect treatment response only 2 weeks after the start of treatment is the shortest interval yet reported, Dr. Chen said. In a study published last year, she and her colleagues reported that another PET radiotracer, 3´-deoxy-3´-[¹⁸F]-fluorothymidine (¹⁸F-FLT), could be used to monitor the response of recurrent high-grade gliomas to treatment (J. Nucl. Med. 2012;53:29-36). However, change in response to treatment with bevacizumab (Avastin) could not be detected with ¹⁸F-FLT until 6 weeks after starting therapy in that study, compared with 2 weeks for ¹⁸F-FDOPA in the current study.

The ¹⁸F-FDOPA technique of assessing metabolic tumor volume as early as 2 weeks after starting bevacizumab proved to be a significant predictor of overall and progression-free survival. The 17 metabolic responders survived a median of 12.1 months, compared with 3.5 months for 11 nonresponders. In comparison, when MRI was used to determine response, the survival difference shrank (12.9 months vs. 9.0 months). All patients in the study eventually died.

The investigators chose to use bevacizumab because "it is the most effective treatment," with a significant treatment response of 50% instead of 5%-10% with other drugs, Dr. Chen said in an interview. "But in terms of monitoring, it doesn’t matter which agent is used for treatment."

¹⁸F-FDOPA is normally used to assess the striatal dopaminergic system in patients with movement disorders. But it works in assessing tumor treatment response because the higher metabolic rate of cancer cells causes greater uptake of the tracer through a phenylalanine and tyrosine transporter. Conventional MRI assessments for tumor recurrence cannot distinguish tumor from scar tissue left by surgery or radiation, and cannot determine the amount of change until 1.5 to 3 months, according to Dr. Chen.

In eight of nine discrepant cases between PET and MRI, ¹⁸F-FDOPA PET demonstrated treatment response earlier than MRI.

The study was supported by grants from the National Cancer Institute and the Department of Energy. Dr. Chen had no relevant disclosures.

A PET imaging protocol using an amino acid analog radiotracer in patients with recurrent high-grade gliomas identified responses to treatment with bevacizumab as early as 2 weeks after starting therapy in a prospective study.

In the 28-patient pilot study, the metabolic tumor volume measured in follow-up PET scans with 6-¹⁸F-fluoro-L-DOPA (¹⁸F-FDOPA) at 2 and 6 weeks after the baseline scan proved to be the most significant predictor of survival with the method.

There is currently no reliable way to predict treatment response noninvasively in patients with malignant glioma, which has only 6% overall survival at 5 years. Chemotherapeutics have toxic side effects and are expensive, "so from the patient’s point of view, if a treatment doesn’t work, it’s important to get that information as early as possible," said the senior investigator of the study, Dr. Wei Chen of the division of molecular and medical pharmacology at the University of California, Los Angeles.

The ability to detect treatment response only 2 weeks after the start of treatment is the shortest interval yet reported, Dr. Chen said. In a study published last year, she and her colleagues reported that another PET radiotracer, 3´-deoxy-3´-[¹⁸F]-fluorothymidine (¹⁸F-FLT), could be used to monitor the response of recurrent high-grade gliomas to treatment (J. Nucl. Med. 2012;53:29-36). However, change in response to treatment with bevacizumab (Avastin) could not be detected with ¹⁸F-FLT until 6 weeks after starting therapy in that study, compared with 2 weeks for ¹⁸F-FDOPA in the current study.

The ¹⁸F-FDOPA technique of assessing metabolic tumor volume as early as 2 weeks after starting bevacizumab proved to be a significant predictor of overall and progression-free survival. The 17 metabolic responders survived a median of 12.1 months, compared with 3.5 months for 11 nonresponders. In comparison, when MRI was used to determine response, the survival difference shrank (12.9 months vs. 9.0 months). All patients in the study eventually died.

The investigators chose to use bevacizumab because "it is the most effective treatment," with a significant treatment response of 50% instead of 5%-10% with other drugs, Dr. Chen said in an interview. "But in terms of monitoring, it doesn’t matter which agent is used for treatment."

¹⁸F-FDOPA is normally used to assess the striatal dopaminergic system in patients with movement disorders. But it works in assessing tumor treatment response because the higher metabolic rate of cancer cells causes greater uptake of the tracer through a phenylalanine and tyrosine transporter. Conventional MRI assessments for tumor recurrence cannot distinguish tumor from scar tissue left by surgery or radiation, and cannot determine the amount of change until 1.5 to 3 months, according to Dr. Chen.

In eight of nine discrepant cases between PET and MRI, ¹⁸F-FDOPA PET demonstrated treatment response earlier than MRI.

The study was supported by grants from the National Cancer Institute and the Department of Energy. Dr. Chen had no relevant disclosures.

A PET imaging protocol using an amino acid analog radiotracer in patients with recurrent high-grade gliomas identified responses to treatment with bevacizumab as early as 2 weeks after starting therapy in a prospective study.

In the 28-patient pilot study, the metabolic tumor volume measured in follow-up PET scans with 6-¹⁸F-fluoro-L-DOPA (¹⁸F-FDOPA) at 2 and 6 weeks after the baseline scan proved to be the most significant predictor of survival with the method.

There is currently no reliable way to predict treatment response noninvasively in patients with malignant glioma, which has only 6% overall survival at 5 years. Chemotherapeutics have toxic side effects and are expensive, "so from the patient’s point of view, if a treatment doesn’t work, it’s important to get that information as early as possible," said the senior investigator of the study, Dr. Wei Chen of the division of molecular and medical pharmacology at the University of California, Los Angeles.

The ability to detect treatment response only 2 weeks after the start of treatment is the shortest interval yet reported, Dr. Chen said. In a study published last year, she and her colleagues reported that another PET radiotracer, 3´-deoxy-3´-[¹⁸F]-fluorothymidine (¹⁸F-FLT), could be used to monitor the response of recurrent high-grade gliomas to treatment (J. Nucl. Med. 2012;53:29-36). However, change in response to treatment with bevacizumab (Avastin) could not be detected with ¹⁸F-FLT until 6 weeks after starting therapy in that study, compared with 2 weeks for ¹⁸F-FDOPA in the current study.

The ¹⁸F-FDOPA technique of assessing metabolic tumor volume as early as 2 weeks after starting bevacizumab proved to be a significant predictor of overall and progression-free survival. The 17 metabolic responders survived a median of 12.1 months, compared with 3.5 months for 11 nonresponders. In comparison, when MRI was used to determine response, the survival difference shrank (12.9 months vs. 9.0 months). All patients in the study eventually died.

The investigators chose to use bevacizumab because "it is the most effective treatment," with a significant treatment response of 50% instead of 5%-10% with other drugs, Dr. Chen said in an interview. "But in terms of monitoring, it doesn’t matter which agent is used for treatment."

¹⁸F-FDOPA is normally used to assess the striatal dopaminergic system in patients with movement disorders. But it works in assessing tumor treatment response because the higher metabolic rate of cancer cells causes greater uptake of the tracer through a phenylalanine and tyrosine transporter. Conventional MRI assessments for tumor recurrence cannot distinguish tumor from scar tissue left by surgery or radiation, and cannot determine the amount of change until 1.5 to 3 months, according to Dr. Chen.

In eight of nine discrepant cases between PET and MRI, ¹⁸F-FDOPA PET demonstrated treatment response earlier than MRI.

The study was supported by grants from the National Cancer Institute and the Department of Energy. Dr. Chen had no relevant disclosures.