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Updated: Dec 11, 2025
Live-3D-Cell Immunocytochemistry Assays of Pediatric Diffuse Midline Glioma
Published on: November 11, 2021
PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models
Umberto Tosi1, Harikrishna Kommidi2, Oluwaseyi Adeuyan1
1Department of Neurological Surgery, Weill Cornell Medicine, New York, NY 10065, USA.
Abstract:
Efforts at altering the dismal prognosis of pediatric midline gliomas focus on direct delivery strategies like convection-enhanced delivery (CED), where a cannula is implanted into tumor. Successful CED treatments require confirmation of tumor coverage, dosimetry, and longitudinal in vivo pharmacokinetic monitoring. These properties would be best determined clinically with image-guided dosimetry using theranostic agents. In this study, we combine CED with novel, molecular-grade positron emission tomography (PET) imaging and show how PETobinostat, a novel PET-imageable HDAC inhibitor, is effective against DIPG models. PET data reveal that CED has significant mouse-to-mouse variability; imaging is used to modulate CED infusions to maximize tumor saturation. The use of PET-guided CED results in survival prolongation in mouse models; imaging shows the need of CED to achieve high brain concentrations. This work demonstrates how personalized image-guided drug delivery may be useful in potentiating CED-based treatment algorithms and supports a foundation for clinical translation of PETobinostat.
Insights
This study introduces PETobinostat, a novel PET-imageable drug, for treating pediatric midline gliomas. Image-guided convection-enhanced delivery (CED) with PETobinostat improved survival in DIPG models by optimizing drug distribution.
Area of Science:
- Oncology
- Neuro-oncology
- Radiochemistry
Background:
- Pediatric midline gliomas, including diffuse intrinsic pontine glioma (DIPG), have a poor prognosis.
- Direct drug delivery strategies like convection-enhanced delivery (CED) are being explored but require precise monitoring.
- Image-guided dosimetry with theranostic agents is crucial for optimizing CED treatments.
Purpose of the Study:
- To evaluate the efficacy of a novel PET-imageable HDAC inhibitor, PETobinostat, delivered via CED in DIPG models.
- To demonstrate the utility of molecular-grade positron emission tomography (PET) imaging for guiding CED and monitoring drug distribution.
- To assess the impact of image-guided CED on therapeutic outcomes and drug concentrations in the brain.
Main Methods:
- Combination of convection-enhanced delivery (CED) with novel molecular-grade positron emission tomography (PET) imaging.
- Administration of PETobinostat, a PET-imageable histone deacetylase (HDAC) inhibitor, in DIPG mouse models.
- Utilizing PET imaging to assess and modulate CED infusion variability, aiming to maximize tumor saturation.
Main Results:
- PET imaging revealed significant variability in CED drug distribution among individual mice.
- Image-guided adjustments to CED infusions successfully enhanced tumor coverage.
- PET-guided CED with PETobinostat demonstrated survival prolongation in DIPG mouse models.
- Imaging confirmed the necessity of CED for achieving high therapeutic drug concentrations in the brain.
Conclusions:
- Personalized, image-guided drug delivery can significantly enhance CED-based treatment strategies for pediatric brain tumors.
- PETobinostat shows promise as a theranostic agent for image-guided therapy in DIPG.
- This study provides a foundation for the clinical translation of PET-guided CED with PETobinostat.
