Hyperpolarized Carbon-13 Metabolic Imaging Differentiates Distinctive Molecular Phenotypes in Diffuse Midline Gliomas

Area of Science:

• Oncology
• Radiology
• Metabolic Imaging

Background:

• Diffuse midline gliomas (DMGs) are heterogeneous pediatric brainstem tumors with a specific histone mutation.
• Existing imaging modalities struggle to differentiate molecular subtypes of DMGs.
• Understanding tumor heterogeneity is crucial for targeted treatment strategies.

Purpose of the Study:

• To investigate the feasibility of hyperpolarized carbon-13 (¹³C) MR metabolic imaging for differentiating molecular features in H3K27M-mutant DMGs.
• To assess the potential of ¹³C MR metabolic imaging in characterizing tumor hypoxia and lactate dehydrogenase-A (LDH-A) activity.
• To compare metabolic profiles of two distinct DMG xenografts (SF8628 and SF7761).

Main Methods:

• Utilized hyperpolarized [1-¹³C]pyruvate injection in rats implanted with SF8628 or SF7761 DMG xenografts.
• Acquired ¹³C MR metabolic imaging data on a 3T scanner.
• Performed immunohistochemical staining for LDH-A and carbonic anhydrase-IX.

Main Results:

• ¹³C metabolic imaging revealed significantly higher ratios of lactate to pyruvate, lactate to total carbon, and normalized lactate in SF8628 compared to SF7761.
• Elevated lactate levels in SF8628 correlated with increased LDH-A and carbonic anhydrase-IX expression.
• These findings suggest a highly hypoxic condition in SF8628 contributing to increased pyruvate-to-lactate conversion.

Conclusions:

• Hyperpolarized ¹³C MR metabolic imaging can noninvasively differentiate molecular features of DMGs.
• This technique shows promise for characterizing molecular hypoxia and LDH-A activity in pediatric brainstem gliomas.
• Advanced metabolic imaging may aid in personalized treatment approaches for DMGs.