TY - JOUR
T1 - Enhancing tissue permeability with MRI guided preclinical focused ultrasound system in rabbit muscle
T2 - From normal tissue to VX2 tumor
AU - Sun, Yao
AU - Xiong, Xiaobing
AU - Pandya, Darpan
AU - Jung, Youngkyoo
AU - Mintz, Akiva
AU - Hayasaka, Satoru
AU - Wadas, Thaddeus J.
AU - Li, King C.P.
PY - 2017/6/28
Y1 - 2017/6/28
N2 - High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, 111In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of 111In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24 h after systematic delivery of 111In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors.
AB - High Intensity Focused Ultrasound (HIFU) is an emerging noninvasive, nonionizing physical energy based modality to ablate solid tumors with high power, or increase local permeability in tissues/tumors in pulsed mode with relatively low power. Compared with traditional ablative HIFU, nondestructive pulsed HIFU (pHIFU) is present in the majority of novel applications recently developed for enhancing the delivery of drugs and genes. Previous studies have demonstrated the capability of pHIFU to change tissue local permeability for enhanced drug delivery in both mouse tumors and mouse muscle. Further study based on bulk tissues in large animals and clinical HIFU system revealed correlation between therapeutic effect and thermal parameters, which was absent in the previous mouse studies. In this study, we further investigated the relation between the therapeutic effect of pHIFU and thermal parameters in bulky normal muscle tissues based on a rabbit model and a preclinical HIFU system. Correlation between therapeutic effect and thermal parameters was confirmed in our study on the same bulk tissues although different HIFU systems were used. Following the study in bulky normal muscle tissues, we further created bulky tumor model with VX2 tumors implanted on both hind limbs of rabbits and investigated the feasibility to enhance tumor permeability in bulky VX2 tumors in a rabbit model using pHIFU technique. A radiolabeled peptidomimetic integrin antagonist, 111In-DOTA-IA, was used following pHIFU treatment in our study to target VX2 tumor and serve as the radiotracer for follow-up single-photon emission computed tomography (SPECT) scanning. The results have shown significantly elevated uptake of 111In-DOTA-IA in the area of VX2 tumors pretreated by pHIFU compared with the control VX2 tumors not being pretreated by pHIFU, and statistical analysis revealed averaged 34.5% enhancement 24 h after systematic delivery of 111In-DOTA-IA in VX2 tumors pretreated by pHIFU compared with the control VX2 tumors.
KW - In
KW - High intensity focused ultrasound
KW - Image guided drug delivery
KW - MRI
KW - Rabbit model
KW - SPECT
KW - Tissue permeability
KW - Translational study
KW - VX2 tumor
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UR - http://www.scopus.com/inward/citedby.url?scp=85018491861&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2017.04.017
DO - 10.1016/j.jconrel.2017.04.017
M3 - Article
C2 - 28412225
AN - SCOPUS:85018491861
VL - 256
SP - 1
EP - 8
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
ER -