Studies of Skeletal Tracer Kinetics. III. Tc-99m(Sn)methylenediphosphonate Uptake in the Canine Tibia as a Function of Blood Flow

: Experiments were performed in 14 dogs to study the effect of changes in bone blood flow on the tibial uptake of the skeletal tracer Tc-99m(Sn)methylenediphosphonate (Tc-99m MDP). Aortic blood was diverted through a pulsatile-flow pump in order to monitor and control femoral arterial blood flow. Tibial nutrient perfusion, as measured with labeled microspheres, paralleled the changes in arterial flow. We found that increments in bone blood flow up to four times normal produced only minimal augmentation of Tc-99m MDP uptake (mean = 33%), a markedly nonproportional relationship. The data points clustered about a predicted curve produced by perturbing the rate constants of a seven-compartment model obtained in normal dogs. These findings indicate that bone uptake of Tc-99m MDP is diffusion-limited, and they therefore cast doubt upon the validity of a method used for many years for estimating bone blood flow, the so-called skeletal tracer clearance technique. Nerve section, performed in 14 other dogs, augmented Tc-99m MDP uptake by about 50% at supranormal flows, suggesting a parallel-flow model of the microcirculation in bone, under sympathetic control. Such a model satisfactorily explains many scintigraphic findings in disease states.