title: Evaluation of 188Re-labeled PEGylated nanoliposome as a radionuclide therapeutic agent in an orthotopic glioma-bearing rat model.
abstract: OBJECTIVE
  In this study, the (188)Re-labeled PEGylated nanoliposome ((188)Re-liposome) was prepared and evaluated as a therapeutic agent for glioma.
  
  
  METHODS
  The reporter cell line, F98(luc) was prepared via Lentivector expression kit system and used to set up the orthotopic glioma-bearing rat model for non-invasive bioluminescent imaging. The maximum tolerated dose applicable in Fischer344 rats was explored via body weight monitoring of the rats after single intravenous injection of (188)Re-liposome with varying dosages before the treatment study. The OLINDA/EXM 1.1 software was utilized for estimating the radiation dosimetry. To assess the therapeutic efficacy, tumor-bearing rats were intravenously administered (188)Re-liposome or normal saline followed by monitoring of the tumor growth and animal survival time. In addition, the histopathological examinations of tumors were conducted on the (188)Re-liposome-treated rats.
  
  
  RESULTS
  By using bioluminescent imaging, the well-established reporter cell line (F98(luc)) showed a high relationship between cell number and its bioluminescent intensity (R(2)=0.99) in vitro; furthermore, it could also provide clear tumor imaging for monitoring tumor growth in vivo. The maximum tolerated dose of (188)Re-liposome in Fischer344 rats was estimated to be 333 MBq. According to the dosimetry results, higher equivalent doses were observed in spleen and kidneys while very less were in normal brain, red marrow, and thyroid. For therapeutic efficacy study, the progression of tumor growth in terms of tumor volume and/or tumor weight was significantly slower for the (188)Re-liposome-treated group than the control group (P<0.05). As a result, the lifespan of glioma-bearing rats treated with (188)Re-liposome was prolonged 10.67% compared to the control group.
  
  
  CONCLUSIONS
  The radiotherapeutic evaluation by dosimetry and survival studies have demonstrated that passive targeting (188)Re-liposome via systemic administration can significantly prolong the lifespan of orthotopic glioma-bearing rats while maintaining reasonable systemic radiation safety. Therefore, (188)Re-liposome could be a potential therapeutic agent for glioblastoma multiforme treatment.
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Feng-Yun J
authors.initials: FY
authors.lastname: Huang
authors.affiliation: Institute of Nuclear Energy Research, Longtan, Taiwan.
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
authors.affiliation: Institute of Nuclear Energy Research, Longtan, Taiwan.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Institute of Nuclear Energy Research, Longtan, Taiwan.
authors.forename: Liang-Cheng
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Institute of Nuclear Energy Research, Longtan, Taiwan.
authors.forename: Wei-Hsin
authors.initials: WH
authors.lastname: Hsu
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Chang
authors.affiliation: Department of Biomedical Engineering and Environmental Sciences, National Tsing Hua University, Hsinchu, Taiwan.
authors.forename: Jem-Mau
authors.initials: JM
authors.lastname: Lo
mesh_terms: D000818:Animals; D005910:Glioma / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D008081:Liposomes / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D053758:Nanoparticles / Q000737:chemistry / Q000627:therapeutic use; D009374:Neoplasms, Experimental / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology; D011868:Radioisotopes / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D051381:Rats; D012211:Rhenium / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use; D014018:Tissue Distribution
chemical_list: D008081:Liposomes; D011868:Radioisotopes; D019275:Radiopharmaceuticals; D012211:Rhenium
keywords: 188Re; bioluminescent imaging; glioma; liposome; radionuclide therapy