Biodistribution and pharmacokinetics of transgenic pig-produced recombinant human factor IX (rhFIX) in rats.
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.
Chang
Chih-Hsien
CH
Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, ROC.
Chou
Ta-Kai
TK
Yang
Chi-Yu
CY
Chang
Tsui-Jung
TJ
Wu
Yu-Hsien
YH
Lee
Te-Wei
TW
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
D007457:Iodine Radioisotopes; D011994:Recombinant Proteins; D005164:Factor IX