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^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

21 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 (US)
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

Funding

All animal experiments were carried out in compliance with the Institutional Animal Care and Usage Committee (IACUC) guidelines of Washington University. This work is supported by Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (MC-II-2017-661, Y.L.), The Children’s Hospital Foundation (J.B.R.), and NIH (R01EB027223 and R01MH116981, H.C.).

Keywords

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

ASJC Scopus subject areas

General Materials Science

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10.1021/acsanm.0c02297

Cite this

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

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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 = "Funding Information: All animal experiments were carried out in compliance with the Institutional Animal Care and Usage Committee (IACUC) guidelines of Washington University. This work is supported by Children{\textquoteright}s Discovery Institute of Washington University and St. Louis Children{\textquoteright}s Hospital (MC-II-2017-661, Y.L.), The Children{\textquoteright}s Hospital Foundation (J.B.R.), and NIH (R01EB027223 and R01MH116981, H.C.). Publisher Copyright: {\textcopyright} ",

year = "2020",

month = nov,

day = "25",

doi = "10.1021/acsanm.0c02297",

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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

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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

N1 - Funding Information: All animal experiments were carried out in compliance with the Institutional Animal Care and Usage Committee (IACUC) guidelines of Washington University. This work is supported by Children’s Discovery Institute of Washington University and St. Louis Children’s Hospital (MC-II-2017-661, Y.L.), The Children’s Hospital Foundation (J.B.R.), and NIH (R01EB027223 and R01MH116981, H.C.). Publisher Copyright: ©

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

Abstract

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Keywords

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