Journal
SCIENCE ADVANCES
Volume 6, Issue 30, Pages -Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abb4105
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Funding
- Cristian Rivera Foundation
- Olivia Boccuzzi Foundation
- Fly a Kite Foundation
- McKenna Claire Foundation
- Lyonhearted Foundation
- Brooke Healey Foundation
- Isabella Rose Romano Foundation
- Lily LaRue Foundation
- Samuel Jeffers Childhood Cancer Foundation
- Ty Louis Campbell Foundation
- Children's Brain Tumor Family Foundation
- Alex Lemonade Stand Foundation (Innovation Grant)
- Department of Defense [CA160373]
- Christian Koehler Foundation
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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 PET obinostat.
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