Invalidity of single-passage measurements of the extraction of bone-seeking tracers in rats and rabbits.

Single-passage experiments in which bone-seeking tracers are injected arterially at the same time as microspheres to determine an extraction ratio are only valid if the maximum transit time through bone is less than the minimum recirculation time. This validity was investigated by injecting various intravascular and more diffusible tracers into the hearts or aortas of rats and rabbits at different times before the rapid cessation of circulation. At no time between 4 and 60 s after injection did the bone concentration of any of the tracers fall to negligible values. Removal of unbound tracer is therefore not complete before recirculation starts, and the single-passage technique is invalid. Measurements of bone blood flow based on the clearance of 18F cannot be substantiated, as its extraction is flow dependent.