Diffuse intrinsic pontine glioma (DIPG) is an invasive pediatric brainstem malignancy exclusively in children without effective treatment due to the often-intact blood-brain tumor barrier (BBTB), an impediment to the delivery of therapeutics. Herein, we used focused ultrasound (FUS) to transiently open BBTB and delivered radiolabeled nanoclusters (64Cu-CuNCs) to tumors for positron emission tomography (PET) imaging and quantification in a mouse DIPG model. First, we optimized FUS acoustic pressure to open the blood-brain barrier (BBB) for the effective delivery of 64Cu-CuNCs to pons in wild-type mice. Then, the optimized FUS pressure was used to deliver radiolabeled agents in DIPG mouse. Magnetic resonance imaging (MRI)-guided FUS-induced BBTB opening was demonstrated using a low-molecular-weight, short-lived 68Ga-DOTA-ECL1i radiotracer and PET/CT before and after treatment. We then compared the delivery efficiency of 64Cu-CuNCs to DIPG tumor with and without FUS treatment and demonstrated the FUS-enhanced delivery and time-dependent diffusion of 64Cu-CuNCs within the tumor.

Original languageEnglish
Pages (from-to)11129-11134
Number of pages6
JournalACS Applied Nano Materials
Issue number11
StatePublished - Nov 25 2020


  • diffuse intrinsic pontine glioma
  • focused ultrasound
  • magnetic resonance imaging
  • nanoclusters
  • positron emission tomography


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