Imaging with new biomarker tracks

Researchers from UT Southwestern’s Peter O’Donnell Jr. Brain Institute and Harold C. Simmons Comprehensive Cancer Center collaborated with investigators in the Advanced Imaging Research Center to identify 2HG (2-hydroxyglutarate), a metabolite that is produced in gliomas that carry IDH (isocitrate dehydrogenase) gene mutations.

Using MR spectroscopy, the team announced in 2012 that they could detect 2HG in the tumour with high sensitivity and specificity. This next-step study showed that 2HG can be useful in tracking the disease, researchers said.

‘This is the first non-invasive biomarker for brain cancer and represents a major advance for the field. Our current imaging is not nearly as precise and takes a longer time to see results,’ said senior author Dr. Maher, who holds the Theodore H. Strauss Professorship in Neuro-Oncology. ‘Within a week of starting treatment, we know whether we hit the target’. This new method will be a much more rapid way of assessing the therapy – allowing the physician to know to stop treatments that aren’t working or continue treatments that are.’

Most biomarkers are in the blood, so identifying biomarkers that can be tracked without drawing blood or obtaining a tissue biopsy is particularly valuable, said Dr. A. Dean Sherry, Director of the Advanced Imaging Research Center and Professor of Radiology at UT Southwestern, and Professor of Chemistry at UT Dallas, where he holds the Cecil H. and Ida Green Distinguished Chair in Systems Biology.

The technique also may serve as a model to develop other imaging biomarkers for the brain, and already is being used to learn more about the biology of glioma, the most common type of brain cancer.

‘In terms of research, the biomarker is a window’ into IDH-mutant glioma biology and we are using it to learn more about how the tumour grows, responds to therapy, and ultimately becomes resistant to treatment,’ said lead author Dr. Changho Choi, Professor of Radiology and with the Advanced Imaging Research Center, where the study was performed using a dedicated research MR scanner.

2HG tracking also could prove useful in diagnosing some brain tumours in which typical surgical procedures to obtain tissue samples can’t be done. That may be because the tumour isn’t accessible, such as near the brainstem, or when trying to get a sample could cause neurological damage. These patients are excluded from clinical trials because of the lack of available tumour tissue for diagnostic analyses.

‘We established in this study that 2HG levels in these tumours can be used to make a presumptive’ molecular diagnosis of an IDH mutation, based solely on imaging,’ said Dr. Choi.

UT Southwestern Medical Center