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PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.

TitlePET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.
Publication TypeJournal Article
Year of Publication2020
AuthorsTosi U, Kommidi H, Adeuyan O, Guo H, Maachani UBhanu, Chen N, Su T, Zhang G, Pisapia DJ, Dahmane N, Ting R, Souweidane MM
JournalSci Adv
Volume6
Issue30
Paginationeabb4105
Date Published2020 Jul
ISSN2375-2548
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.

DOI10.1126/sciadv.abb4105
Alternate JournalSci Adv
PubMed ID32832670
PubMed Central IDPMC7439439