title: Biodistribution and pharmacokinetics of transgenic pig-produced recombinant human factor IX (rhFIX) in rats.
abstract: BACKGROUND
  Recombinant human factor IX (rhFIX) is a 56 kDa glycoprotein with full biological activity providing a guarantee of freedom from blood-borne viral contamination in the therapy of hemophilia B, but no data are available on the distribution of transgenic pig-produced rhFIX post injection (p.i.). Therefore, an 131I-radiolabeled rhFIX was developed to evaluate the distribution of rhFIX in rats.
  
  
  METHODS
  rhFIX was labeled with the lodogen method. 131I-rhFIX (25 microCi/25 microg/200 microl/rat) was intravenously injected through the tail vein in normal Sprague-Dawley (SD) rats and the biodistribution was examined from 5 min to 72 h p.i.. The pharmacokinetics were also evaluated from 5 min to 96 h p.i.
  
  
  RESULTS
  The radiolabeled efficiency and radiochemical purity of 131I-rhFIX was over 96% and 98%, respectively. The biodistribution study showed that the rhFIX chiefly accumulated in the liver. The distribution and elimination half-life (t(1/2alpha) and t(1/2beta)) of 131I-rhFIX were 0.82 and 9.34 h, respectively. The maximum concentration in the plasma (Cmax) and the area under the concentration versus time curve (AUC(INF)) of 131I-rhFIX in rats were 3.09% injected dose (ID)/g and 15.3 h x % ID/g.
  
  
  CONCLUSIONS
  The transgenic pig-produced rhFIX is mostly retained in the liver and the preclinical biodistribution and pharmacokinetic studies of 131I radiolabeled rhFIX are helpful for researching its biological effect in vivo.
authors.affiliation: Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, ROC.
authors.forename: Chih-Hsien
authors.initials: CH
authors.lastname: Chang
authors.forename: Ta-Kai
authors.initials: TK
authors.lastname: Chou
authors.forename: Chi-Yu
authors.initials: CY
authors.lastname: Yang
authors.forename: Tsui-Jung
authors.initials: TJ
authors.lastname: Chang
authors.forename: Yu-Hsien
authors.initials: YH
authors.lastname: Wu
authors.forename: Te-Wei
authors.initials: TW
authors.lastname: Lee
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified / Q000378:metabolism*; D001921:Brain / Q000378:metabolism; D005164:Factor IX / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000378:metabolism; D006801:Humans; D007457:Iodine Radioisotopes; D007553:Isotope Labeling; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000493:pharmacokinetics*; D013154:Spleen / Q000378:metabolism; D013552:Swine; D014018:Tissue Distribution
chemical_list: D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D005164:Factor IX