Oncotarget

Research Papers:

Simultaneous sentinel lymph node computed tomography and locoregional chemotherapy for lymph node metastasis in rabbit using an iodine-docetaxel emulsion

Honsoul Kim, Eun-Ji Jang, Sang Kyum Kim, Woo Jin Hyung, Dong Kyu Choi, Soo-Jeong Lim and Joon Seok Lim _

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Oncotarget. 2017; 8:27177-27188. https://doi.org/10.18632/oncotarget.15679

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Abstract

Honsoul Kim1,2, Eun-Ji Jang3, Sang Kyum Kim4, Woo Jin Hyung5, Dong Kyu Choi6, Soo-Jeong Lim3, Joon Seok Lim1,2

1Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea

2Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul, Republic of Korea

3Department of Integrative Bioscience and Bioengineering, Sejong University, Seoul, Republic of Korea

4Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea

5Department of Surgery, Yonsei University College of Medicine, Seoul, Republic of Korea

6New Drug Development Center, Daegu-Gyeongbuk, Medical Innovation Foundation, Daegu, Republic of Korea

Correspondence to:

Joon Seok Lim, email: jslim1@yuhs.ac

Soo-Jeong Lim, email: sjlim@sejong.ac.kr

Keywords: sentinel lymph node, computed tomography (CT), iodine-docetaxel emulsion, lymph node metastasis, locoregional chemotherapy

Received: November 08, 2016     Accepted: February 06, 2017     Published: February 24, 2017

ABSTRACT

Purpose: A sentinel lymph node (SLN) tracer can gain multi-functionality by combining it with additional components. We developed a SLN tracer consisting of iodine and docetaxel and applied it as a theragnostic nanoparticle to simultaneously perform SLN computed tomography (CT) lymphography and locoregional chemotherapy of the draining lymphatic system.

Results: Docetaxel could be loaded in iodine emulsions at a drug-to-surfactant weight ratio as high as that in the drug formulation Taxotere®. The particle size and drug concentration were stable during storage for up to 3 months in optimized nanoemulsions. Popliteal LN enhancement on CT was observed in all healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) 12 hours after injection. The rate of SLN metastasis was significantly lower in the treatment group (29.4%, 5/17) than in the non-treatment group (70.6%, 12/17) (P=0.038).

Material and Methods: We prepared a nanoemulsion carrying both iodine and docetaxel in a single structure by optimizing the composition of surfactants surrounding the inner iodized oil core. CT was performed 12 hours after subcutaneous injection of the emulsion in healthy rabbits (n=3) and VX2 tumor-implanted rabbits (n=6) for SLN imaging. Next, we tested the effect of treatment by histopathologically assessing the popliteal LN metastasis rate in VX2 tumor-implanted rabbits 7 days after subcutaneous injection of the emulsion (treatment group, n=17) and comparing it with that of non-treatment group rabbits (n=17).

Conclusions: We developed an iodine-docetaxel emulsion and demonstrated that it can be applied to simultaneously achieve CT SLN imaging and local chemotherapy against nodal metastasis.


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