|Title||PET, image-guided HDAC inhibition of pediatric diffuse midline glioma improves survival in murine models.|
|Publication Type||Journal Article|
|Year of Publication||2020|
|Authors||Tosi U, Kommidi H, Adeuyan O, Guo H, Maachani UBhanu, Chen N, Su T, Zhang G, Pisapia DJ, Dahmane N, Ting R, Souweidane MM|
|Date Published||2020 Jul|
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.
|Alternate Journal||Sci Adv|
|PubMed Central ID||PMC7439439|