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

Abstract

OBJECTIVE:

The aim of the present study is to investigate the biologic effects of internal irradiation and the therapeutic effectiveness of 131I-labeled arginine-glycine-aspartate (RGD)-bovine serum albumin (BSA)-polycaprolactone (PCL) (131I-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 αvβ3 were observed by confocal microscopy. Flow cytometry was used to assay apoptosis. The biologic effects of internal irradiation and the therapeutic efficacy of 131I-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 131I-labeled BSA-PCL (131I-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 131I-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 131I-labeled liposome (p < 0.05). The decrease in body weight in the group treated with 131I-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 131I-RGD-BSA-PCL and 131I-BSA-PCL, respectively.

CONCLUSION:

RGD-BSA-PCL has excellent cellular binding in vitro in a non-small cell lung cancer xenograft model. Furthermore, 131I-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.

• Authors: Hui Ming, Lei Fang, Jingmei Gao, Chengxia Li, Yanhui Ji, Yiming Shen, Yiming Hu, Ning Li, Jin Chang, Wei Li, Jian Tan
• Journal: AJR. American journal of roentgenology (AJR Am J Roentgenol) Vol. 208 Issue 5 Pg. 1116-1126 (May 2017) ISSN: 1546-3141 [Electronic] United States
• PMID: 28301223 (Publication Type: Journal Article)

Chemical References

• Iodine Radioisotopes
• Liposomes
• Oligopeptides
• Polyesters
• Radiopharmaceuticals
• polycaprolactone
• Serum Albumin, Bovine
• arginyl-glycyl-aspartic acid

Topics

• Animals
• Apoptosis
• Cattle
• Cell Line, Tumor
• Flow Cytometry
• Heterografts
• Humans
• Iodine Radioisotopes (pharmacokinetics, pharmacology)
• Liposomes
• Lung Neoplasms (diagnostic imaging, radiotherapy)
• Mice
• Microscopy, Confocal
• Molecular Targeted Therapy (methods)
• Nanoparticles
• Oligopeptides (pharmacokinetics, pharmacology)
• Polyesters (pharmacokinetics, pharmacology)
• Radiopharmaceuticals (pharmacokinetics, pharmacology)
• Random Allocation
• Serum Albumin, Bovine (pharmacokinetics, pharmacology)
• Single Photon Emission Computed Tomography Computed Tomography
• Theranostic Nanomedicine