PT  - JOURNAL ARTICLE
AU  - Tosi, Umberto
AU  - Kommidi, Harikrishna
AU  - Adeuyan, Oluwaseyi
AU  - Guo, Hua
AU  - Maachani, Uday Bhanu
AU  - Chen, Nandi
AU  - Su, Taojunfeng
AU  - Zhang, Guoan
AU  - Pisapia, David J.
AU  - Dahmane, Nadia
AU  - Ting, Richard
AU  - Souweidane, Mark M.
TI  - PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models
AID  - 10.1126/sciadv.abb4105
DP  - 2020 Jul 01
TA  - Science Advances
PG  - eabb4105
VI  - 6
IP  - 30
4099  - http://advances.sciencemag.org/content/6/30/eabb4105.short
4100  - http://advances.sciencemag.org/content/6/30/eabb4105.full
SO  - Sci Adv2020 Jul 01; 6
AB  - 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.