Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma

Ying-Hsia Shih,1,2 Xi-Zhang Lin,3 Chung-Hsin Yeh,1 Cheng-Liang Peng,1,2 Ming-Jium Shieh,2,4 Wuu-Jyh Lin,1 Tsai-Yueh Luo1,51Isotope Application Division, Institute of Nuclear Energy Research, Longtan, 2Institute of Biomedical Engineering, National Taiwan University, Taipei, 3Department of Internal M...

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Autores principales:	Shih YH, Lin XZ, Yeh CH, Peng CL, Shieh MJ, Lin WJ, Luo TY
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
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spelling	oai:doaj.org-article:c600ca79209e4cb4b06aa000fc4af8492021-12-02T03:58:31ZPreparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma1178-2013https://doaj.org/article/c600ca79209e4cb4b06aa000fc4af8492014-09-01T00:00:00Zhttp://www.dovepress.com/preparation-and-therapeutic-evaluation-of-188re-thermogelling-emulsion-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Ying-Hsia Shih,1,2 Xi-Zhang Lin,3 Chung-Hsin Yeh,1 Cheng-Liang Peng,1,2 Ming-Jium Shieh,2,4 Wuu-Jyh Lin,1 Tsai-Yueh Luo1,51Isotope Application Division, Institute of Nuclear Energy Research, Longtan, 2Institute of Biomedical Engineering, National Taiwan University, Taipei, 3Department of Internal Medicine, National Cheng Kung University, Tainan, 4Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, 5Institute of Radiological Science, Central Taiwan University of Science and Technology, Taichung, TaiwanAbstract: Radiolabeled Lipiodol® (Guerbet, Villepinte, France) is routinely used in hepatoma therapy. The temperature-sensitive hydrogel polyethylene glycol-b-poly-DL-lactic acid-co-glycolic acid-b-polyethylene glycol triblock copolymer is used as an embolic agent and sustained drug release system. This study attempted to combine the polyethylene glycol-b-poly-DL-lactic acid-co-glycolic acid-b-polyethylene glycol hydrogel and radio-labeled Lipiodol to form a new radio-thermogelling emulsion, rhenium-188–N,N’-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride–Lipiodol/hydrogel (188Re-ELH). The therapeutic potential of 188Re-ELH was evaluated in a rodent hepatoma model. Rhenium-188 chelated with N,N’-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride was extracted with Lipiodol to obtain rhenium-188–N,N’-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride–Lipiodol (188Re-EL), which was blended with the hydrogel in equal volumes to develop 188Re-ELH. The 188Re-ELH phase stability was evaluated at different temperatures. Biodistribution patterns and micro-single-photon emission computed tomography/computed tomography images in Sprague Dawley rats implanted with the rat hepatoma cell line N1-S1 were observed after in situ tumoral injection of ~3.7 MBq 188Re-ELH. The therapeutic potential of 188Re-EL (48.58±3.86 MBq/0.1 mL, n=12) was evaluated in a 2-month survival study using the same animal model. The therapeutic effects of 188Re-ELH (25.52±4.64 MBq/0.1 mL, n=12) were evaluated and compared with those of 188Re-EL. The responses were assessed by changes in tumor size and survival rates. The 188Re-ELH emulsion was stable in the gel form at 25°C–35°C for >52 hours. Biodistribution data and micro-single-photon emission computed tomography/computed tomography images of the 188Re-ELH group indicated that most activity was selectively observed in hepatomas. Long-term 188Re-ELH studies have demonstrated protracted reductions in tumor volumes and positive effects on the survival rates (75%) of N1-S1 hepatoma-bearing rats. Conversely, the 2-month survival rate was 13% in the control sham group. Therapeutic responses differed significantly between the two groups (P<0.005). Thus, the hydrogel enhanced the injection stability of 188Re-EL in an animal hepatoma model. Given the synergistic results, direct 188Re-ELH intratumoral injection is a potential therapeutic alternative for hepatoma treatment.Keywords: 188Re-ECD-Lipiodol, hydrogel, hepatoma, thermogelling emulsionShih YHLin XZYeh CHPeng CLShieh MJLin WJLuo TYDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 4191-4201 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Shih YH Lin XZ Yeh CH Peng CL Shieh MJ Lin WJ Luo TY Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
description	Ying-Hsia Shih,1,2 Xi-Zhang Lin,3 Chung-Hsin Yeh,1 Cheng-Liang Peng,1,2 Ming-Jium Shieh,2,4 Wuu-Jyh Lin,1 Tsai-Yueh Luo1,51Isotope Application Division, Institute of Nuclear Energy Research, Longtan, 2Institute of Biomedical Engineering, National Taiwan University, Taipei, 3Department of Internal Medicine, National Cheng Kung University, Tainan, 4Department of Oncology, National Taiwan University Hospital and College of Medicine, Taipei, 5Institute of Radiological Science, Central Taiwan University of Science and Technology, Taichung, TaiwanAbstract: Radiolabeled Lipiodol® (Guerbet, Villepinte, France) is routinely used in hepatoma therapy. The temperature-sensitive hydrogel polyethylene glycol-b-poly-DL-lactic acid-co-glycolic acid-b-polyethylene glycol triblock copolymer is used as an embolic agent and sustained drug release system. This study attempted to combine the polyethylene glycol-b-poly-DL-lactic acid-co-glycolic acid-b-polyethylene glycol hydrogel and radio-labeled Lipiodol to form a new radio-thermogelling emulsion, rhenium-188–N,N’-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride–Lipiodol/hydrogel (188Re-ELH). The therapeutic potential of 188Re-ELH was evaluated in a rodent hepatoma model. Rhenium-188 chelated with N,N’-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride was extracted with Lipiodol to obtain rhenium-188–N,N’-1,2-ethanediylbis-L-cysteine diethyl-ester dihydrochloride–Lipiodol (188Re-EL), which was blended with the hydrogel in equal volumes to develop 188Re-ELH. The 188Re-ELH phase stability was evaluated at different temperatures. Biodistribution patterns and micro-single-photon emission computed tomography/computed tomography images in Sprague Dawley rats implanted with the rat hepatoma cell line N1-S1 were observed after in situ tumoral injection of ~3.7 MBq 188Re-ELH. The therapeutic potential of 188Re-EL (48.58±3.86 MBq/0.1 mL, n=12) was evaluated in a 2-month survival study using the same animal model. The therapeutic effects of 188Re-ELH (25.52±4.64 MBq/0.1 mL, n=12) were evaluated and compared with those of 188Re-EL. The responses were assessed by changes in tumor size and survival rates. The 188Re-ELH emulsion was stable in the gel form at 25°C–35°C for >52 hours. Biodistribution data and micro-single-photon emission computed tomography/computed tomography images of the 188Re-ELH group indicated that most activity was selectively observed in hepatomas. Long-term 188Re-ELH studies have demonstrated protracted reductions in tumor volumes and positive effects on the survival rates (75%) of N1-S1 hepatoma-bearing rats. Conversely, the 2-month survival rate was 13% in the control sham group. Therapeutic responses differed significantly between the two groups (P<0.005). Thus, the hydrogel enhanced the injection stability of 188Re-EL in an animal hepatoma model. Given the synergistic results, direct 188Re-ELH intratumoral injection is a potential therapeutic alternative for hepatoma treatment.Keywords: 188Re-ECD-Lipiodol, hydrogel, hepatoma, thermogelling emulsion
format	article
author	Shih YH Lin XZ Yeh CH Peng CL Shieh MJ Lin WJ Luo TY
author_facet	Shih YH Lin XZ Yeh CH Peng CL Shieh MJ Lin WJ Luo TY
author_sort	Shih YH
title	Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
title_short	Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
title_full	Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
title_fullStr	Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
title_full_unstemmed	Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma
title_sort	preparation and therapeutic evaluation of 188re-thermogelling emulsion in rat model of hepatocellular carcinoma
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/c600ca79209e4cb4b06aa000fc4af849
work_keys_str_mv	AT shihyh preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma AT linxz preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma AT yehch preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma AT pengcl preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma AT shiehmj preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma AT linwj preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma AT luoty preparationandtherapeuticevaluationof188rethermogellingemulsioninratmodelofhepatocellularcarcinoma
_version_	1718401515977179136

Preparation and therapeutic evaluation of 188Re-thermogelling emulsion in rat model of hepatocellular carcinoma

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