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.
journal_name
Sci Advjournal_title
Science advancesauthors
Tosi U,Kommidi H,Adeuyan O,Guo H,Maachani UB,Chen N,Su T,Zhang G,Pisapia DJ,Dahmane N,Ting R,Souweidane MMdoi
10.1126/sciadv.abb4105subject
Has Abstractpub_date
2020-07-24 00:00:00pages
eabb4105issue
30issn
2375-2548pii
abb4105journal_volume
6pub_type
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