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. Materials and Methods: rhFIX was labeled with the Iodogen method. ¹³¹I-rhFIX (25 μCi/25 μg/200 μl/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_1/2α and t_1/2β) of ¹³¹I-rhFIX were 0.82 and 9.34 h, respectively. The maximum concentration in the plasma (C_max) 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×% ID/g. Conclusion: 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.