Quantitative studies of bone using F-18-fluoride and Tc-99m-methylene diphosphonate: evaluation of renal and whole-blood kinetics

We report a study of the renal and whole-blood kinetics of F-18-fluoride an d Tc-99m-methylene diphosphonate (Tc-99m-MDP) and their effect on the evalu ation of the skeletal kinetics of the two bone tracers. Data were obtained during an investigation of postmenopausal women taking hormone replacement therapy who were compared with untreated, age-matched controls. After intra venous injection of F-18-fluoride (1 MBq), Tc-99m-MDP (1 MBq), Cr-51-ethyle nediaminetetraacetic acid (Cr-51-EDTA) (3 MBq) and I-125-human serum albumi n (I-125-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. Cr-51-EDTA data were used to eval uate the glomerular filtration rate (GFR) and the completeness of each time d urine collection. I-125-HSA data were used to evaluate the plasma volume and the red cell uptake of the other three tracers. At 4 h, the cumulative urine excretions (and standard deviations, SDs) were: Tc-99m-MDP, 58.2% (4. 8%); F-18-fluoride, 36.1% (5.7%); Cr-51-EDTA, 81.5% (4.5%). Plots of the re nal clearance of F-18-fluoride against urine volume showed that urine flow rates greater than 5 ml.min(-1) were necessary to ensure a constant renal c learance of F-18 and hence stable conditions for the evaluation of bone tra cer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of Tc-99m-MDP. For MDP, the evaluation of skeletal kinetics requi res data on protein binding so that calculations can be performed for free MDP. In the present study, protein binding of MDP was evaluated from the ra tio of total Tc-99m-MDP renal clearance to GFR based on the principle that free Tc-99m-MDP is a GFR tracer. Between 0 and 4 h after injection, the fra ctional protein binding of MDP increased linearly with time, changing from 21 +/-5% immediately after injection to 58 +/-5% at 4 h. Although red cell uptake of Tc-99m-MDP was negligible, for F-18-fluoride around 30% of circul ating tracer was transported in red cells. In view of the data showing the rapid transport of F-18-fluoride across the red cell membrane, bone kinetic data for F-18 are more accurately reported as whole-blood clearance rather than plasma clearance. ((C) 2001 Lippincott Williams & Wilkins).