title: Antitumor Effect of Nanoparticle131I-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 of131I-labeled arginine-glycine-aspartate (RGD)-bovine serum albumin (BSA)-polycaprolactone (PCL) (131I-RGD-BSA-PCL) in murine lung cancer models.
  
  
  METHODS
  The target binding and cellular uptake of NCI-H460 lung cancer cells overexpressing integrin αvβ3were observed by confocal microscopy. Flow cytometry was used to assay apoptosis. The biologic effects of internal irradiation and the therapeutic efficacy of131I-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]) of131I-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 of131I-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 of131I-labeled liposome (p < 0.05). The decrease in body weight in the group treated with131I-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 with131I-RGD-BSA-PCL and131I-BSA-PCL, respectively.
  
  
  CONCLUSIONS
  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.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Hui
authors.initials: H
authors.lastname: Ming
authors.affiliation: 2 Department of Materials Laboratory, School of Life Sciences, Tianjin, P. R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Jingmei
authors.initials: J
authors.lastname: Gao
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Chengxia
authors.initials: C
authors.lastname: Li
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Ji
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Shen
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Yiming
authors.initials: Y
authors.lastname: Hu
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Li
authors.affiliation: 2 Department of Materials Laboratory, School of Life Sciences, Tianjin, P. R. China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chang
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: 1 Department of Nuclear Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, P. R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Tan
mesh_terms: D000818:Animals; D017209:Apoptosis; D002417:Cattle; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D064593:Heterografts; D006801:Humans; D007457:Iodine Radioisotopes / Q000493:pharmacokinetics / Q000494:pharmacology*; D008081:Liposomes; D008175:Lung Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*; D051379:Mice; D018613:Microscopy, Confocal; D058990:Molecular Targeted Therapy / Q000379:methods*; D053758:Nanoparticles; D009842:Oligopeptides / Q000493:pharmacokinetics / Q000494:pharmacology*; D011091:Polyesters / Q000493:pharmacokinetics / Q000494:pharmacology*; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics / Q000494:pharmacology*; D011897:Random Allocation; D012710:Serum Albumin, Bovine / Q000493:pharmacokinetics / Q000494:pharmacology*; D000072098:Single Photon Emission Computed Tomography Computed Tomography; D000068936:Theranostic Nanomedicine
chemical_list: D007457:Iodine Radioisotopes; D008081:Liposomes; D009842:Oligopeptides; D011091:Polyesters; D019275:Radiopharmaceuticals; C016240:polycaprolactone; D012710:Serum Albumin, Bovine; C047981:arginyl-glycyl-aspartic acid
keywords: SPECT/CT; arginine-glycine-aspartate; nanoliposome; non–small cell lung carcinoma; radioiodine therapy