Toxicology of intrahepatic arterial administration of interventional phosphorus-32 glass microspheres to domestic pigs

Objective To evaluate the toxic response to intrahepatic arterial administr ation of radioactive phosphorus-32 glass microspheres (P-32-GMS) in domesti c pigs. Methods Through selective catheterization of hepatic artery, P-32-GMS was i nfused to 5 healthy domestic pigs in a dosage equivalent to the therapeutic dose for human being, and P-31-GMS was infused to other 5 healthy domestic pigs. Two pigs served as the whole course blank controls. One pig from eac h group was surrendered to euthanasia at week 1, 2, 4, 8 and 16, respective ly, and liver biopsies were performed on the rest of pigs at the correspond ing time points. Liver tissues from different sites were taken for light an d electron microscopy. The ultrastructural histopathological changes were e valuated semiquantitatively. Through selective catheterization of hepatic P -32-GMS was infused to 5 healthy domestic Results The accumulative amount of P-32-GMS in the target tissue attained m ore than 90% of the total dose administrated. Histologically, abnormal hepa tocytes were easily found at week 1 or 2. At week 4 they were less than at week 1 or 2, and endothelium of the sinuses were damaged prominently. At we ek 8 they were scarcely seen, and liver tissue recovered gradually. The his tological features of liver tissue restored to normal at week 16. Semiquant itative analysis of ultrastructural morphology in the experimental group sh owed no statistical difference (P > 0.50) between the nuclear abnormality ( N-abn) and mitochrondrial variability (M-var) at week 1 or 2, but revealed prominent difference (P < 0.01, P < 0.001) as compared with those in other groups. In the experimental group the N-abn in tissues showed no significan t difference (P > 0.20) between week 8 and week 16. Conclusion P-32-GMS internal irradiation at the dosage equivalent to human therapeutic dosage exerts reversible injury to domestic pig liver tissue, a nd it takes more than 8 weeks for the injured liver tissue to recover.