The extraction from the blood of phosphate compounds by canine bone

Uptake by bone of 99mTc-labeled pyrophosphate (PPi) and ethane-1-hydroxy-1,1-diphosphonate (EHDP) involves passage through capillaries in the Haversian system, extracellular fluid space, and membrane of osteoblasts before adsorption onto available apatite surfaces. Passage through capillaries was studied by the outflow-dilution technique in a canine tibia model in mongrel dogs. 51Cr-labeled albumin (nondiffusible reference tracer), sucrose (diffusible reference tracer), PPi, and EHDP were injected into the isolated nutrient tibial artery. Blood was collected from the ipsilateral femoral vein every 15 sec for 2 min. Emax, the apparent extraction at the time of the peaks of the dilution curves, is influenced little by back diffusion; for PP, Emax (mean +/- SD) = 0.42 +/- 0.08 (N = 4); for EHDP, Emax = 0.27 +/- 0.05 (N = 10). Net extraction (apparent fractional retention by bone at 2 min) was 0.36 +/- 0.1 for PP. Emax for 85Sr chloride and 18F sodium in our laboratory is 0.69 +/- 0.11 (N = 14) and 0.70 +/- 0.008 (N = 9), respectively. Permeabilities (P) were calculated by PS = -Fs loge (1-Emax), where Fs = plasma flow and S = capillary surface; the ratio of P for EHDP to P for sucrose was 0.71 which is similar to the ratio of diffusion coefficients, 0.78. The data suggest that EHDP and probably also PPi pass through the capillaries by passive diffusion. As expected, the extraction through capillary walls for EHDP and PPi was lower than that for 85Sr and 18F because of their larger molecular size.