Antitumor Effect of Nanoparticle I-131-Labeled Arginine-Glycine-Aspartate-Bovine Serum Albumin-Polycaprolactone in Lung Cancer

作者：Ming, Hui; Fang, Lei; Gao, Jingmei; Li, Chengxia; Ji, Yanhui; Shen, Yiming; Hu, Yiming; Li, Ning; Chang, Jin; Li, Wei^*; Tan, Jian

来源：American Journal of Roentgenology, 2017, 208(5): 1116-1126.

DOI：10.2214/AJR.16.16947

• arginine-glycine-aspartate
• nanoliposome
• non-small cell lung carcinoma
• radioiodine therapy
• SPECT/CT

OBJECTIVE. The aim of the present study is to investigate the biologic effects of internal irradiation and the therapeutic effectiveness of I-131-labeled arginine-glycine-aspartate (RGD)-bovine serum albumin (BSA)-polycaprolactone (PCL) (I-131-RGD-BSA-PCL) in murine lung cancer models.
MATERIALS AND METHODS. The target binding and cellular uptake of NCI-H460 lung cancer cells overexpressing integrin alpha(v)beta(3) were observed by confocal microscopy. Flow cytometry was used to assay apoptosis. The biologic effects of internal irradiation and the therapeutic efficacy of I-131-RGD-BSA-PCL were investigated in murine lung cancer models; tumor size, body weight, histopathologic findings, and SPECT/CT imaging findings were also monitored.
RESULTS. In vitro uptake studies performed using confocal microscopy showed that, after 1 hour of incubation with RGD-BSA-PCL or BSA-PCL, visible fluorescence was present in the cells, and after 8 hours, the florescent signal did not disappear. The mean (+/- SE) tumor uptake level (i.e., the percentage of the injected dose per gram of tissue [% ID/g]) of I-131-labeled BSA-PCL (I-131-BSA-PCL) at 24 and 72 hours after injection was 11.06% +/- 2.15% ID/g and 3.83% +/- 0.87% ID/g, respectively, which is significantly higher than the uptake levels noted for other organs (p < 0.05). The level of tumor uptake of I-131-RGD-BSA-PCL at 24 and 72 hours after injection was 39.49% +/- 6.06% ID/g and 6.97% +/- 1.43% ID/g, respectively, which is significantly higher than that of I-131-labeled liposome (p < 0.05). The decrease in body weight in the group treated with I-131-RGD-BSA-PCL was only 3.5% of the original body weight and was much lower than noted in the group receiving saline (i.e., 21.5% of original body weight). The median survival time for the therapeutic groups was prolonged to 27 days and 23 days after treatment with I-131-RGD-BSA-PCL and I-131-BSA-PCL, respectively.
CONCLUSION. RGD-BSA-PCL has excellent cellular binding in vitro in a non-small cell lung cancer xenograft model. Furthermore, I-131-RGD-BSA-PCL was evaluated as an imaging agent and is an interesting candidate for targeting therapies in the non-small cell lung cancer xenograft model.

• 出版日期2017-5
• 单位天津医科大学