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Preparation and therapeutic evaluation of (188)Re-thermogelling emulsion in rat model of hepatocellular carcinoma.
- Source :
-
International journal of nanomedicine [Int J Nanomedicine] 2014 Sep 02; Vol. 9, pp. 4191-201. Date of Electronic Publication: 2014 Sep 02 (Print Publication: 2014). - Publication Year :
- 2014
-
Abstract
- 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 ((188)Re-ELH). The therapeutic potential of (188)Re-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 ((188)Re-EL), which was blended with the hydrogel in equal volumes to develop (188)Re-ELH. The (188)Re-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 (188)Re-ELH. The therapeutic potential of (188)Re-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 (188)Re-ELH (25.52±4.64 MBq/0.1 mL, n=12) were evaluated and compared with those of (188)Re-EL. The responses were assessed by changes in tumor size and survival rates. The (188)Re-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 (188)Re-ELH group indicated that most activity was selectively observed in hepatomas. Long-term (188)Re-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 (188)Re-EL in an animal hepatoma model. Given the synergistic results, direct (188)Re-ELH intratumoral injection is a potential therapeutic alternative for hepatoma treatment.
- Subjects :
- Animals
Carcinoma, Hepatocellular pathology
Drug Combinations
Emulsions chemical synthesis
Emulsions chemistry
Hydrogels chemical synthesis
Hydrogels chemistry
Iodized Oil chemistry
Liver Neoplasms, Experimental pathology
Male
Organometallic Compounds chemistry
Polyethylene Glycols
Polyglactin 910
Radioisotopes chemistry
Rats
Rats, Sprague-Dawley
Rhenium chemistry
Survival Analysis
Tissue Distribution
Carcinoma, Hepatocellular radiotherapy
Emulsions therapeutic use
Hydrogels therapeutic use
Liver Neoplasms, Experimental radiotherapy
Radioisotopes therapeutic use
Rhenium therapeutic use
Subjects
Details
- Language :
- English
- ISSN :
- 1178-2013
- Volume :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of nanomedicine
- Publication Type :
- Academic Journal
- Accession number :
- 25214783
- Full Text :
- https://doi.org/10.2147/IJN.S66346