Limitations of radioactive microspheres as tracers for bone blood flow and extraction ratio studies

Radioactive microspheres have been used for measuring bone blood flow and the extraction ratios of bone-seeking radionuclides, but we have shown that the technique is not completely valid. Bone uptake of 18F and 85Sr was compared with that of microspheres simultaneously injected into the heart or aorta of rats and rabbits under a variety of conditions. In single-passage experiments with quick killing to avoid recirculation, attention was focused on the tibiae and femora which could be dissected quickly to avoid post-mortem migration. For the rest of the skeleton, the effect of the latter was minimized by allowing recirculation for 5 min and comparing blood flow determinations in conjunction wit a cardiac output measurement. The apparent extraction ratio of 18F was variable and always exceeded unity in the single-passage experiments. With recirculation, there were significant differences between the extraction ratios for some bones, and the ratios sometimes exceeded unity. Extraction ratios for 85Sr were similarly variable, but lower. When 85Sr was compared directly with 18F, the relative extraction ratio was 0.8, with little variation between bones or animals. It is concluded that the flux of microspheres entering the vasculature of bone is not representative of blood flow, owing to the removal of some microspheres in pre-osseous capillary beds. Microspheres are therefore not a satisfactory standard for the determination of extraction ratios.