18F-DOPA-PET Detects Early Response in IDH-Mutant Glioma

Key Clinical Summary: 

• ¹⁸F-DOPA-PET detected metabolic responses not captured by conventional MRI, identifying treatment activity in patients classified as having stable disease by RANO 2.0 criteria.
• Metabolic tumor volume reductions were associated with prolonged tumor control, suggesting PET-based parameters may have prognostic value during IDH inhibitor therapy.
• Advanced imaging modalities may provide earlier and more sensitive response assessment, supporting their potential integration into monitoring strategies for patients with IDH-mutant glioma receiving targeted therapy.

Diego Prost, MD, Pitié-Salpêtrière University Hospital, Paris, France, discusses findings from a real-world imaging analysis evaluating early response assessment in patients with IDH1/2-mutant glioma treated with IDH inhibitors. 

These findings suggest that ¹⁸F-DOPA-PET and advanced MRI techniques may detect treatment response earlier and more sensitively than conventional MRI in patients receiving IDH-targeted therapy, supporting their potential integration into response assessment strategies for IDH-mutant gliomas.

Transcript:

My name is Diego Prost, I’m a medical oncologist at Pitié-Salpêtrière Hospital in Paris. In this video, I will present our recent work on how ¹⁸F-DOPA-PET can improve the way we assess treatment response in IDH-mutant glioma patients treated with IDH inhibitors.

Diffuse gliomas are the most common malignant primary brain tumors and about ⅓ of them have a mutation in the IDH1/2 genes. In recent years, small-molecule IDH inhibitors, such as ivosidenib or vorasidenib, have emerged as promising targeted therapies for patients with IDH-mutant gliomas. However, in daily practice, we rely on conventional MRI to evaluate response. 

Under IDH inhibitors, radiologic responses are often rare, and many patients are classified as having stable disease for long periods of time. This creates 2 main problems: First, we lack early biomarkers that tell us whether the patient is truly benefiting from treatment and second, in a population that is often clinically stable, it can be difficult to decide whether to continue or stop treatment. 

PET imaging, like ¹⁸F-DOPA-PET, is more sensitive for detecting tumor functional activity, and it is already used in many centers to help with diagnosis and follow-up. To address this gap, we performed a retrospective, single-center study of 20 patients with IDH-mutant astrocytoma or oligodendroglioma treated with ivosidenib or vorasidenib. We used RANO 2.0 criteria for MRI assessment and PET RANO 1.0 criteria for PET assessment, focusing mainly on metabolic tumor volume and tumor-to-background ratios.

Our first key finding is that we did not observe any formal radiologic response on MRI. In contrast, ¹⁸F-DOPA-PET detected a significant metabolic response in half of the patients. We observed 1 complete metabolic response and 9 partial metabolic responses based on reductions in metabolic tumor volume and tracer uptake. We also found 2 patients who showed an increase in their FLAIR lesion at the first evaluation, a phenomenon already described with IDH inhibitors during the first 6 months of treatment. In these patients, PET showed a metabolic response despite the FLAIR increase. When we looked at outcomes, the functional response on PET was not just a cosmetic change, a reduction in metabolic tumor volume was associated with longer progression-free survival. 

So what does this mean for clinical practice– First, in patients treated with IDH inhibitors, adding ¹⁸F-DOPA-PET gives us extra information about tumor dynamics that we would miss using only MRI. Second, ¹⁸F-DOPA-PET seems to be a sensitive tool to detect early metabolic changes and to distinguish true progression from treatment-related fluctuations. [Lastly], our data suggest that metabolic tumor volume on PET could serve as an early marker of benefit for IDH inhibitors.

Of course, this is a preliminary study in a small cohort, larger prospective studies and standardized imaging protocols will be needed before these approaches can be widely adopted.

Source: 

Prost D, Nichelli L, Rozenblum L, et al. 18F-DOPA-PET and advanced MRI improve treatment response assessment in IDH1/2-mutant gliomas treated with IDH inhibitors. Clin Cancer Res. Published online: February 2, 2026. doi:10.1158/1078-0432.CCR-25-0279