Chang Chih-Hsien, Chou Ta-Kai, Yang Chi-Yu, Chang Tsui-Jung, Wu Yu-Hsien, Lee Te-Wei
Division of Isotope Application, Institute of Nuclear Energy Research, Taoyuan, ROC.
In Vivo. 2008 Nov-Dec;22(6):693-7.
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.
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.
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.
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.
重组人凝血因子IX（rhFIX）是一种具有完全生物活性的56 kDa糖蛋白，在治疗B型血友病时可确保无血源病毒污染，但尚无关于转基因猪生产的rhFIX注射后分布的数据。因此，开发了一种131I放射性标记的rhFIX来评估其在大鼠体内的分布。
采用氯胺T法对rhFIX进行标记。将131I-rhFIX（25微居里/25微克/200微升/只大鼠）经尾静脉注射到正常的Sprague-Dawley（SD）大鼠体内，在注射后5分钟至72小时检测其生物分布。同时在注射后5分钟至96小时评估其药代动力学。
131I-rhFIX的放射性标记效率和放射化学纯度分别超过96%和98%。生物分布研究表明，rhFIX主要蓄积在肝脏。131I-rhFIX的分布半衰期（t(1/2α)）和消除半衰期（t(1/2β)）分别为0.82小时和9.34小时。大鼠血浆中131I-rhFIX的最大浓度（Cmax）和浓度-时间曲线下面积（AUC(INF)）分别为3.09%注射剂量（ID）/克和15.3小时×%ID/克。
转基因猪生产的rhFIX大多保留在肝脏中，131I放射性标记的rhFIX的临床前生物分布和药代动力学研究有助于研究其体内生物学效应。
