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

doi:10.1021/acsanm.0c02297

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 journal › Article › peer-review

19 Scopus citations

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 language	English
Pages (from-to)	11129-11134
Number of pages	6
Journal	ACS Applied Nano Materials
Volume	3
Issue number	11
DOIs	https://doi.org/10.1021/acsanm.0c02297
State	Published - Nov 25 2020

Keywords

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

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10.1021/acsanm.0c02297

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Zhang, X., Ye, D., Yang, L., Yue, Y., Sultan, D., Pacia, C. P., Pang, H., Detering, L., Heo, G. S., Luehmann, H., Choksi, A., Sethi, A., Limbrick, D. D., Becher, O. J., Tai, Y. C., Rubin, J. B., Chen, H., & Liu, Y. (2020). Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma. ACS Applied Nano Materials, 3(11), 11129-11134. https://doi.org/10.1021/acsanm.0c02297

@article{a4986755a1ed4d92b3e2b3cf1ec307a4,

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

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.",

keywords = "diffuse intrinsic pontine glioma, focused ultrasound, magnetic resonance imaging, nanoclusters, positron emission tomography",

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

note = "Publisher Copyright: {\textcopyright} ",

year = "2020",

month = nov,

day = "25",

doi = "10.1021/acsanm.0c02297",

language = "English",

volume = "3",

pages = "11129--11134",

journal = "ACS Applied Nano Materials",

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Zhang, X, Ye, D, Yang, L, Yue, Y, Sultan, D, Pacia, CP, Pang, H, Detering, L, Heo, GS, Luehmann, H, Choksi, A, Sethi, A, Limbrick, DD, Becher, OJ, Tai, YC , Rubin, JB , Chen, H & Liu, Y 2020, 'Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma', ACS Applied Nano Materials, vol. 3, no. 11, pp. 11129-11134. https://doi.org/10.1021/acsanm.0c02297

TY - JOUR

T1 - Magnetic Resonance Imaging-Guided Focused Ultrasound-Based Delivery of Radiolabeled Copper Nanoclusters to Diffuse Intrinsic Pontine Glioma

AU - Zhang, Xiaohui

AU - Ye, Dezhuang

AU - Yang, Lihua

AU - Yue, Yimei

AU - Sultan, Deborah

AU - Pacia, Christopher Pham

AU - Pang, Hannah

AU - Detering, Lisa

AU - Heo, Gyu Seong

AU - Luehmann, Hannah

AU - Choksi, Ankur

AU - Sethi, Abhishek

AU - Limbrick, David D.

AU - Becher, Oren J.

AU - Tai, Yuan Chuan

AU - Rubin, Joshua B.

AU - Chen, Hong

AU - Liu, Yongjian

PY - 2020/11/25

Y1 - 2020/11/25

N2 - 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.

AB - 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.

KW - diffuse intrinsic pontine glioma

KW - focused ultrasound

KW - magnetic resonance imaging

KW - nanoclusters

KW - positron emission tomography

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U2 - 10.1021/acsanm.0c02297

DO - 10.1021/acsanm.0c02297

M3 - Article

C2 - 34337344

AN - SCOPUS:85096027299

SN - 2574-0970

VL - 3

SP - 11129

EP - 11134

JO - ACS Applied Nano Materials

JF - ACS Applied Nano Materials

IS - 11

ER -

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

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