Open AccessMagnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma
Author(s) -
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
Publication year - 2020
Publication title -
acs applied nano materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.227
H-Index - 29
ISSN - 2574-0970
DOI - 10.1021/acsanm.0c02297
Subject(s) - magnetic resonance imaging , pons , glioma , medicine , positron emission tomography , blood–brain barrier , malignancy , nuclear medicine , pathology , cancer research , radiology , central nervous system , anatomy
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 ( 64 Cu-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 effective delivery of 64 Cu-CuNCs to pons in wildtype 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 68 Ga-DOTA-ECL1i radiotracer and PET/CT before and after treatment. We then compared the delivery efficiency of 64 Cu-CuNCs to DIPG tumor with and without FUS treatment and demonstrated the FUS-enhanced delivery and time-dependent diffusion of 64 Cu-CuNCs within the tumor.