Synchronous evaluation of toxico- and pharmaco-dynamics of yttrium-90 by a novel autoradiographic procedure.

ABSTRACT

A synchronous evaluation was performed, using a quick in vivo [2-(14)C]thymidine labeling method, of the toxico- and pharmaco-dynamics of a given dose of yttrium-90 (90Y) at a given time after injection to nude BALB/c mice loaded with 10(7) HuO9 cells. Quantitative data were 14C-microautoradiographs of the liver lobule, intestinal crypts, epiphysial growth plate, secondary ossification center containing pluripotent stem cells, perifollicular zone containing unipotent stem cells in the spleen, and plasmacytoma cells in the osteogenic sarcoma in each mouse following a 10-min labeling with 14C at 0.5, 6, and 24 h after i.v. injection of 90Y. Results show that the cell proliferation rate of the stem cells in respective tissues was markedly suppressed, dependent on time after dosing and the dose of 90Y; 3.7, 37, 370, 3700, and 37,000 kBq per mouse (25 g). In addition to the above, the sensitivity of the proliferation rate was dependent on amitosis or mitosis and the AUC value of 90Y-concentration at specific locations of the cells in the mouse body. The most sensitive cells were the plasmacytoma cells, followed by the pluripotent and unipotent stem cells, the intestinal crypts, epiphysial growth plate, and liver cells.