¹⁸F-DOPA PET Detects Treatment Response Missed by Conventional MRI in IDH-Mutant Glioma

Clinical Summary: 

• Design/Population: This retrospective imaging study evaluated 20 patients with IDH1/2-mutant astrocytoma or oligodendroglioma treated with IDH inhibitors who underwent serial MRI and ¹⁸F-DOPA PET imaging.

• Key Outcomes: Metabolic responses on¹⁸F-DOPA PET, including reductions in tumor-to-background ratios and metabolic tumor volume, were observed in half of patients. PET identified partial or complete responses that were not detected by conventional MRI, which classified all patients as having stable disease.

• Clinical Relevance: These findings support ¹⁸F-DOPA PET and advanced MRI as complementary imaging modalities to conventional RANO 2.0 MRI criteria for assessing treatment response in patients with IDH-mutant glioma receiving IDH inhibitor therapy.

Results from a retrospective imaging study demonstrated that ¹⁸F-DOPA PET identified metabolic responses not detected by conventional MRI in patients with IDH-mutant glioma receiving IDH inhibitor therapy, supporting its role as a complementary imaging modality for treatment assessment.

“Small-molecule inhibitors targeting IDH1/2-mutant proteins have demonstrated benefit in IDH1/2-mutant gliomas,” stated Diego Prost, Pitié-Salpêtrière University Hospital, Paris, France, and coauthors. “However, responses assessed by conventional MRI measurements are infrequent, delayed, and difficult to interpret, highlighting the need for early biomarkers of treatment benefit.” 

In this retrospective study, investigators evaluated 20 patients with IDH1/2-mutant astrocytoma (n = 8) or oligodendroglioma (n = 12) treated with either ivosidenib (n = 4) or vorasidenib (n = 16). All patients underwent serial MRI and ¹⁸F-DOPA PET imaging before and after treatment. MRI assessments included conventional morphologic, volumetric, diffusion, and perfusion imaging, while PET analyses evaluated metabolic tumor volume, total lesion glycolysis, and tumor-to-background ratios. Treatment response was assessed using volumetric MRI, RANO 2.0 criteria, and PET RANO 1.0 criteria.

At analysis, 50% of patients experienced significant reductions in ¹⁸F-DOPA PET parameters, including tumor-to-background ratios and metabolic tumor volume. Using PET-based response criteria, 9 patients achieved a partial response and 1 patient achieved a complete response. In contrast, both conventional morphologic MRI and volumetric MRI classified all patients as having stable disease.

Reductions in metabolic tumor volume on ¹⁸F-DOPA PET were also associated with prolonged tumor control, supporting the potential prognostic value of metabolic imaging during IDH inhibitor treatment.

“These results highlight the potential of ¹⁸F-DOPA PET and advanced MRI sequences as valuable complements to standard RANO 2.0 MRI evaluations for assessing treatment response in glioma patients undergoing IDHi therapy,” concluded Dr Prost et al. 

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