Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma

Xiaohui Zhang, Dezhuang Ye, Lihua Yang, Yimei Yue, Deborah Sultan, Christopher Pham Pacia, Hannah Pang, Lisa Detering, Gyu Seong Heo, Hannah Luehmann, Ankur Choksi, Abhishek Sethi, David D. Limbrick, Oren J. Becher, Yuan Chuan Tai, Joshua B. Rubin, Hong Chen, Yongjian Liu

Research output: Contribution to journalArticlepeer-review

Abstract

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
Volume3
Issue number11
DOIs
StatePublished - Nov 25 2020

Keywords

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

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