Preoperative [ 11 C]methionine PET to personalize treatment decisions in patients with lower-grade gliomas

Background : PET with radiolabelled amino acids is used in the preoperative evaluation of patients with glial neoplasms. This study aimed to assess the role of [ 11 C]methionine (MET) PET in assessing molecular features, tumour extent, and prognosis in newly-diagnosed lower-grade gliomas (LGGs) surgically treated. Methods : 153 patients with a new diagnosis of grade 2/3 glioma who underwent surgery at our Institution and were imaged preoperatively using [ 11 C]MET PET/CT were retrospectively included. [ 11 C]MET PET images were qualitatively and semiquantitatively analyzed using tumour-to-background ratio (TBR). Progression-free survival (PFS) rates were estimated using the Kaplan-Meier method and Cox proportional-hazards regression was used to test the association of clinicopathological and imaging data to PFS. Results : Overall, 111 lesions (73%) were positive, while thirty-two (21%) and ten (6%) were isometabolic and hypometabolic at [ 11 C]MET PET, respectively. [ 11 C]MET uptake was more common in oligodendrogliomas than IDH -mutant astrocytomas (87% vs 50% of cases, respectively). Among [ 11 C]MET-positive gliomas, grade 3 oligodendrogliomas had the highest median TBR max (3.22). In 25% of patients, PET helped to better delineate tumour margins compared to MRI only. In IDH -mutant astrocytomas, higher TBR max values at [ 11 C]MET PET were independent predictors of shorter PFS. Conclusions : This work highlights the role of preoperative [ 11 C]MET PET in estimating the type, assessing tumour extent, and predicting biological behaviour and prognosis of LGGs. Our findings support the implementation of [ 11 C]MET PET in routine clinical practice to better manage these neoplasms. [ 11 C]methionine (MET) PET is widely used to complement to MRI in the preoperative management of patients with gliomas. However, there is still no clear evidence for its added value in lower-grade gliomas (LGGs). This study is the first comprehensive investigation on the diagnostic and prognostic value of amino acid PET in LGGs stratified according to WHO type and other known prognostic factors. We showed that [ 11 C]MET PET is valid for the prospective assessment of LGG type and grade before the availability of a histomolecular diagnosis. Additionally, we demonstrated the complementary role of MRI and [ 11 C]MET PET in delineating of tumour margins before surgery. Finally, for the first time, our findings proved that [ 11 C]MET PET has an independent prognostic role in LGG patients with IDH -mutant astrocytomas. Our results support the routine implementation of [ 11 C]MET PET to personalize treatment decisions and optimize patient management in newly diagnosed LGGs. When looking at LGG types, the great majority (87%) of oligodendroglial tumours included in our cohort showed [ 11 C]MET uptake and they exhibited the highest MTV and TBR values. Accordingly, of a [ 11 C]MET PET-negative lesion support an alternative diagnosis. Conversely, IDH -mutant astrocytomas presented the lowest MTV and TBR values and were PET-negative in half of the patients. IDH -mutant astrocytomas represented 71% of all PET-negative lesions, in particular 80% and 69% of all hypometabolic and isometabolic tumours, respectively. Consequently, cold and isometabolic lesions at [ 11 C]MET PET should raise the suspicion of these specific LGG entities. Our findings were in line with two previous reports by Kebir et al. 25 and Takei et al. 26 , who have described a higher [ 11 C]MET uptake in IDH -mutant, 1p/19q-codeleted LGGs compared to IDH -mutant, 1p/19q-non codeleted tumours. However, the small sample size in both these studies did not allow to find significant differences among LGG types with respect to radiopharmaceutical uptake.