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

• Published in: ACS applied nano materials Vol. 3; no. 11; pp. 11129 - 11134
• Main Authors: Zhang, Xiaohui, Ye, Dezhuang, Yang, Lihua, Yue, Yimei, Sultan, Deborah, Pacia, Christopher Pham, Pang, Hannah, Detering, Lisa, Heo, Gyu Seong, Luehmann, Hannah, Choksi, Ankur, Sethi, Abhishek, Limbrick, David D, Becher, Oren J, Tai, Yuan-chuan, Rubin, Joshua B, Chen, Hong, Liu, Yongjian
• Format: Journal Article
• Language: English
• Published: American Chemical Society 25.11.2020
• Subjects: magnetic resonance imaging; nanoclusters; positron emission tomography; diffuse intrinsic pontine glioma; focused ultrasound
• ISSN: 2574-0970; 2574-0970
• DOI: 10.1021/acsanm.0c02297

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.