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.

MATERIALS AND 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.

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.