Amino acid PET imaging to monitor mIDH inhibitor treatments in patients with refractory IDH-mutant gliomas.

Abstract

PURPOSE: Mutant IDH (mIDH) inhibitors represent a novel therapeutic approach for IDH-mutant gliomas. This study aimed to evaluate the role of amino acid PET in monitoring the response to mIDH inhibitor treatment in patients with refractory IDH-mutant gliomas. METHODS: Patients with confirmed IDH-mutant gliomas who received mIDH inhibitor treatments, ivosidenib or vorasidenib, between February 2022 and November 2024, with baseline [¹⁸F]-FDOPA scans, were included. Lesions were assessed using the RANO 2.0 and PET RANO criteria to determine measurability and, in patients with early follow-up imaging, to predict 6-month progression-free survival (PFS-6). RESULTS: Twenty-two patients were included (mean age: 42.1 ± 10.5 years; 8 women; 14 with IDH-mutant astrocytomas). Among them, 11 underwent follow-up imaging with both MRI and PET within the first 100 days of treatment. At baseline, MRI identified measurable lesions in 10 of 22 patients (45%), whereas amino acid PET identified lesions in 20 of 22 patients (91%) (p < 0.01). In patients with early follow-up, the RANO 2.0 criteria predicted PFS-6 with 91% accuracy (10/11) compared with 82% accuracy (9/11) with PET RANO (p > 0.05). The only discordant case showed progression on PET but stability on MRI, with confirmed clinical progression at 10 months post-treatment initiation. CONCLUSION: Amino acid PET is a valuable tool for identifying measurable lesions in patients with refractory IDH-mutant gliomas. Moreover, in this specific population, its performance for monitoring treatment with mIDH inhibitors is at least comparable to that of MRI. CLINICAL TRIAL REGISTRATION: Trial was registered at ClinicalTrials.gov (NCT07017790) and complied with the principles of the Declaration of Helsinki.