Drug-carrying microbubbles as a theranostic tool in convection-enhanced delivery for brain tumor therapy
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Pin-Yuan Chen1,5, Chih-Kuang Yeh2, Po-Hung Hsu3, Chung-Yin Lin4, Chiung-Yin Huang1, Kuo-Chen Wei1 and Hao-Li Liu1,3,4
1Department of Neurosurgery, Chang Gung Memorial Hospital, Linkou Medical Center and School of Medicine, Chang Gung University, Taoyuan 333, Taiwan
2Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu 30013, Taiwan
3Department of Electrical Engineering, Chang Gung University, Taoyuan 333, Taiwan
4Medical Imaging Research Center, Institute for Radiological Research, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
5Department of Neurosurgery, Chang Gung Memorial Hospital, Keelung 204, Taiwan
Hao-Li Liu, email: [email protected]
Kuo-Chen Wei, email: [email protected]
Keywords: convection-enhanced delivery, microbubbles, magnetic resonance imaging, R2 relaxometry
Received: September 14, 2016 Accepted: February 22, 2017 Published: March 15, 2017
Convection-enhanced delivery (CED) is a promising technique for infusing a therapeutic agent through a catheter with a pressure gradient to create bulk flow for improving drug spread into the brain. So far, gadopentetate dimeglumine (Gd-DTPA) is the most commonly applied surrogate agent for predicting drug distribution through magnetic resonance imaging (MRI). However, Gd-DTPA provides only a short observation duration, and concurrent infusion provides an indirect measure of the exact drug distribution. In this study, we propose using microbubbles as a contrast agent for MRI monitoring, and evaluate their use as a drug-carrying vehicle to directly monitor the infused drug. Results show that microbubbles can provide excellent detectability through MRI relaxometry and accurately represent drug distribution during CED infusion. Compared with the short half-life of Gd-DTPA (1-2 hours), microbubbles allow an extended observation period of up to 12 hours. Moreover, microbubbles provide a sufficiently high drug payload, and glioma mice that underwent a CED infusion of microbubbles carrying doxorubicin presented considerable tumor growth suppression and a significantly improved survival rate. This study recommends microbubbles as a new theranostic tool for CED procedures.
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