title: Rhenium-188 labeled recombinant human plasminogen kringle5 (rhk5) and preliminary biodistribution. Evaluation in mice bearing A549 tumours.
abstract: OBJECTIVE
  Angiogenesis plays a critical role in tumour formation and metastasis. Suitable radiolabeled angiogenesis inhibitor can be used for noninvasive imaging of angiogenesis and radionuclide therapy. Here we prepare rhenium-188 labeled recombinant human plasminogen kringle5 (188Re-rhk5) in a convenient manner than evaluate its properties in A549 lung adenocarcinoma.
  
  
  METHODS
  188Re-rhk5 was obtained by conjugating His group at the C end of rhk5 with fac-[188Re(H2O)3(CO)3]+. Chelating efficiency of fac-[188Re(H2O)3(CO)3]+ and radiolabeling efficiency of 188Re-rhk5 were measured by radio thin-layer chromatography (RTLC). In vitro stability of 188Re-rhk5 was determined in human serum at 37°C and analyzed by RTLC. Competition test was also performed to verify the specificity of binding. A biodistribution study was carried out in nude mice bearing A549 lung adenocarcinoma.
  
  
  RESULTS
  188Re-rhk5 was obtained with a radiolabel efficiency of 66.1%, the radiochemical purity (RCP) can reach 95.2% after purification. 188Re-rhk5 showed high stability in human serum, the RCP was more than 80% even 12 h after incubation. Competition test showed a high binding specificity. Furthermore, this radio-complex was excreted mainly through kidneys and showed specific tumour uptake in mice bearing A549 tumours.
  
  
  CONCLUSIONS
  188Re-rhk5 was prepared by a simple method. Preliminary biodistribution results showed its potential as an agent for possible tumour imaging, therapy and encouraged further investigation.
authors.affiliation: Department of Nuclear Medicine, Shanghai Jiaotong University, School of Medicine, Shanghai, People's Republic of China.
authors.forename: R
authors.initials: R
authors.lastname: Guo
authors.forename: Y
authors.initials: Y
authors.lastname: Ma
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: S
authors.initials: S
authors.lastname: Liang
authors.forename: H
authors.initials: H
authors.lastname: Shen
authors.forename: H
authors.initials: H
authors.lastname: Xu
authors.forename: B
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D007553:Isotope Labeling; D008175:Lung Neoplasms / Q000000981:diagnostic imaging* / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D051379:Mice; D008819:Mice, Nude; D009928:Organ Specificity; D010865:Pilot Projects; D010958:Plasminogen / Q000493:pharmacokinetics; D011868:Radioisotopes / Q000493:pharmacokinetics*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011994:Recombinant Proteins / Q000737:chemistry / Q000493:pharmacokinetics; D012211:Rhenium / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution; D014915:Whole-Body Counting
chemical_list: D011868:Radioisotopes; D019275:Radiopharmaceuticals; D011994:Recombinant Proteins; C571092:recombinant plasminogen kringle5, human; D012211:Rhenium; D010958:Plasminogen