Effect of 18F-DOPA-PET and advanced MRI on treatment response assessment in IDH1/2-mutant gliomas treated with IDH inhibitors.

Abstract

2050 Background: Small-molecule inhibitors targeting IDH1/2-mutant proteins (IDHi) have shown promise as treatments for IDH1/2 -mutant gliomas. However, accurate assessment of response using morphological magnetic resonance imaging (MRI) measurements remains difficult, and the potential of PET imaging with radiolabeled amino acids in this context is yet to be explored. Here, we investigated 3,4-Dihydroxy-6-[18F]-fluoro-L-phenylalanine PET (¹⁸F-DOPA-PET) and MRI responses in IDH1/2 -mutant glioma patients receiving IDHi. Methods: IDH1/2 -mutant glioma patients receiving IDHi as part of trials or expanded access programs were included. Patients had pre- and post-treatment MRI and ¹⁸F-DOPA-PET. Centralized evaluations included 2D/3D measurements on T2-weighted FLAIR images, T1-post contrast, perfusion, and diffusion imaging for MRI, and metabolic tumor volume (MTV), total lesion glycolysis (TLG), and tumor-to-background ratios (TBRs) for ¹⁸F-DOPA-PET. Disease response evaluation using volumetric assessments, RANO 2.0 and PET RANO 1.0 criteria were compared and confronted to outcomes. Results: From 2021 to 2024, 10 patients with IDH1/2 -mutant glioma (3 astrocytoma, 7 oligodendroglioma) receiving IDHi (4 ivosidenib, 6 vorasidenib) were analyzed. Significant reductions in 18 F-DOPA-PET parameters including TBRmean, TBRmax, and MTV were observed in 8/10 patients, aligning with observed changes in perfusion and diffusion imaging. Seven partial responses and one complete response were identified using ¹⁸F-DOPA-PET, while both volumetric and standard 2D morphological MRI assessments indicated stable disease as best response. PET response was correlated with prolonged tumor control. Conclusions: This study highlights 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.