title: Preparation and biodistribution of 188Re-labeled folate conjugated human serum albumin magnetic cisplatin nanoparticles (188Re-folate-CDDP/HSA MNPs) in vivo.
abstract: BACKGROUND
  The purpose of this study was to develop intraperitoneal hyperthermic therapy based on magnetic fluid hyperthermia, nanoparticle-wrapped cisplatin chemotherapy, and magnetic particles of albumin. In addition, to combine the multiple-killing effects of hyperthermal targeting therapy, chemotherapy, and radiotherapy, the albumin-nanoparticle surfaces were linked with radionuclide (188)Re-labeled folic acid ligand ((188)Re-folate-CDDP/HSA).
  
  
  METHODS
  Human serum albumin was labeled with (188)Re using the pre-tin method. Reaction time and optimal conditions of labeling were investigated. The particles were intravenously injected into mice, which were sacrificed at different time points. Radioactivity per gram of tissue of percent injected dose (% ID/g) was measured in vital organs. The biodistribution of (188)Re-folate-CDDP/HAS magnetic nanoparticles was assessed.
  
  
  RESULTS
  Optimal conditions for (188)Re-labeled folate-conjugated albumin combined with cisplatin magnetic nanoparticles were: 0.1 mL of sodium gluconate solution (0.3 mol/L), 0.1 mL of concentrated hydrochloric acid with dissolved stannous chloride (10 mg/mL), 0.04 mL of acetic acid buffer solution (pH 5, 0.2 mol/L), 30 mg of folate-conjugated albumin combined with cisplatin magnetic nanoparticles, and (188)ReO(4) eluent (0.1 mL). The rate of (188)Re-folate-CDDP-HSA magnetic nanoparticle formation exceeded 90%, and radiochemical purity exceeded 95%. The overall labeling rate was 83% in calf serum at 37°C. The major uptake tissues were the liver, kidney, intestine, and tumor after the (188)Re-folate-CDDP/HSA magnetic nanoparticles were injected into nude mice. Uptake of (188)Re-folate-CDDP/HSA magnetic nanoparticles increased gradually after injection, peaked at 8 hours with a value of 8.83 ± 1.71, and slowly decreased over 24 hours in vivo.
  
  
  CONCLUSIONS
  These results indicate that (188)Re-folate-CDDP/HSA magnetic nanoparticles can be used in radionuclide-targeted cancer therapy. Surface-modified albumin nanoparticles with folic acid ligand-labeled radionuclide ((188)Re) were successfully prepared, laying the foundation for a triple-killing effect of thermotherapy, chemotherapy, and radiation therapy.
authors.affiliation: Department of Pathology and Pathophysiology, Medical College, Southeast University, Nanjing, Jiangsu. panyixi-tqs@163.com
authors.forename: Qiu-Sha
authors.initials: QS
authors.lastname: Tang
authors.forename: Dao-Zhen
authors.initials: DZ
authors.lastname: Chen
authors.forename: Wen-Qun
authors.initials: WQ
authors.lastname: Xue
authors.forename: Jing-Ying
authors.initials: JY
authors.lastname: Xiang
authors.forename: Yong-Chi
authors.initials: YC
authors.lastname: Gong
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Cai-Qin
authors.initials: CQ
authors.lastname: Guo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000737:chemistry* / Q000493:pharmacokinetics; D004355:Drug Stability; D005260:Female; D005492:Folic Acid / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D011868:Radioisotopes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D012211:Rhenium / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D012709:Serum Albumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D013696:Temperature; D017971:Tin Compounds / Q000737:chemistry; D014018:Tissue Distribution; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D058185:Magnetite Nanoparticles; D011868:Radioisotopes; D012709:Serum Albumin; D017971:Tin Compounds; C023599:stannous chloride; D012211:Rhenium; D005492:Folic Acid; D002945:Cisplatin