Metabolic characterization of brainstem glioma in children according to 11C-methionine PET/CT data: a retrospective study

INTRODUCTION: One of the main difficulties in prognosis and treatment planning in children with brainstem glioma is rare histological verification of the diagnosis, which prompts increased attention to non-invasive diagnostics using neuroimaging.

OBJECTIVE: To study the metabolic characteristics of brainstem and thalamic tumors in children using PET/CT with ¹¹Cmethionine (Met) in association with MRI results.

MATERIALS AND METHODS: The study included the results of Met PET/CT in 63 children aged 3 to 18 with brainstem gliomas who underwent contrast-enhanced MRI (CE) and ¹¹C-methionine PET/CT before treatment. The analysis was performed on fused PET and MRI images and consisted of visual assessment and calculation of Met tumor-to-brain ratio (TBR) and the metabolic tumor volume.

RESULTS: Tumors were divided into two groups: diffuse intrinsic pontine gliomas (DIPG) and other gliomas (OG). Significant differences between DIPG and OG were found in lesion size and initial tumor bed. No differences were found in the frequency of tumor contrast enhancement (p=0.21). Met high uptake was observed in 72% of DIPG and in 58% of other gliomas without significant differences (p=0.25), but TBR depended on the reference structure: cerebellum or frontal cortex (p=0.00001). Positive or negative Met tumor uptake, as well as TBR, were not associated with either the tumor type or its localization. The relationship between tumor enhancement and Met uptake pattern was found in DIPG.

DISCUSSION: Variability in amino acid transport and metabolism in brainstem tumors did not allow a reliable discrimination between tumor types, which may be due to the similar phenotypic features in DIPG and OG affecting Met uptake. The data obtained are consistent with the results of studies by other groups of authors, which showed that the greatest prognostic value for brainstem tumors is not the histological structure, but the glioma genotype.

CONCLUSION: The absence of a specific pattern of methionine transport and metabolism disorders for diffuse midline glioma limits the significance of metabolic biomarkers in the diagnosis and differential diagnosis of brainstem tumors.

1. Ostrom Q.T., Price M., Ryan K. et al. CBTRUS Statistical Report: Pediatric Brain Tumor Foundation Childhood and Adolescent Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2014–2018 // NeuroOncol. 2022. Vol. 24, Suppl. 3. P. iii1-iii38. doi: 10.1093/neuonc/noac161.

2. Ozerov S.S., Ryzhova M.V., Kumirova E.V. Diffuse brainstem tumors in children. Tumor biology and hope dor a better outcome. Current state of the problem. Burdenko Journal of Neurosurgery, 2021, Vol. 85, No. 4, pp. 77– 86 (In Russ.). doi: 10.17116/neiro20218504177

3. Hassan H., Pinches A., Picton S.V. et al. Survival rates and prognostic predictors of high-grade brain stem gliomas in childhood: a systematic review and meta-analysis // J. Neurooncol. 2017. Vol. 135. P. 13–20. doi: 10.1007/s11060-017-2546-1.

4. Castel D., Philippe C., Calmon R. et al. Histone H3F3A and HIST1H3B K27M mutations define two subgroups of diffuse intrinsic pontine gliomas with different prognosis and phenotypes // Acta. Neuropathol. (Berl.). 2015. Vol. 130, No 6. P. 815–827. doi: 10.1007/s00401-015-1478-0.

5. Mohammad F., Helin K. Oncohistones: drivers of pediatric cancers // Genes Dev. 2017. Vol. 31, No. 23–24. P. 2313–2324. doi: 10.1101/gad.309013.117.

6. Khuong-Quang D.A., Buczkowicz P., Rakopoulos P. et al. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas // Acta Neuropathol. 2012. Vol. 124. No 3. P. 439–447. doi: 10.1007/s00401-012-0998-0.

7. Louis D.N., Perry A., Wesseling P. et al. The 2021 WHO classification of tumors of the central nervous system: a summary // Neuro-Oncol. 2021. Vol. 23, No. 8. P. 1231–1251. doi: 10.1093/neuonc/noab106.

8. Buczkowicz P., Bartels U., Bouffet E. et al. Histopathological spectrum of paediatric diffuse intrinsic pontine glioma: diagnostic and therapeutic implications // Acta Neuropathol. 2014. Vol. 128, No. 4. P. 573–581. doi: 10.1007/s00401-014-1319-6.

9. Green A.L., Kieran M.W. Pediatric brainstem gliomas: new understanding leads to potential new treatments for two very different tumors // Curr. Oncol. Rep. 2015. Vol. 17, No. 12. P. 1–11. doi: 10.1007/s11912-014-0436-7.

10. Leach J.L., Roebker J., Schafer A. et al. MR imaging features of diffuse intrinsic pontine glioma and relationship to overall survival: report from the International DIPG Registry // Neuro-Oncol. 2020. Vol. 22, No 11. P. 1647–1657.

11. Chiang J., Diaz A.K., Makepeace L. et al. Clinical, imaging, and molecular analysis of pediatric pontine tumors lacking characteristic imaging features of DIPG // Acta. Neuropathologica Communications. 2020. Vol. 8. Р. 57. doi: 10.1186/s40478-020-00930-9.

12. Tinkle C.L., Duncan E.C., Doubrovin M. et al. Evaluation of 11C-methionine PET and anatomic MRI association in diffuse intrinsic pontine glioma // J. Nucl. Med. 2019. Vol. 60, No 3. P. 312–319. doi: 10.2967/jnumed.118.212514.

13. Zhao X., Li D., Qiao Z. et al. 11C methionine PET imaging characteristics in children with diffuse intrinsic pontine gliomas and relationship to survival and H3 K27M mutation status // Eur. J. Nucl. Med. Mol. Imaging. 2023. Vol. 50, No. 6. P. 1709–1719. doi: 10.1007/s00259-022-06105-z.

14. Susin D., Skvortsova T. Normal [11C]-methionine PET uptake in the brain in children before and after treatment // Eur. J. Nucl. Med. Mol. Imaging. 2019. Vol. 46, Suppl 1. P. S328. doi: 10.1007/s00259-019-04486-2.