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

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Abstract
We report a study of the renal and whole-blood kinetics of 18F-fluoride and 99mTc-methylene diphosphonate (99mTc-MDP) and their effect on the evaluation 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 intravenous injection of 18F-fluoride (1 MBq), 99mTc-MDP (1 MBq), 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA) (3 MBq) and 125I-human serum albumin (125I-HSA) (0.25 MBq), multiple blood samples and urine collections were taken between 0 and 4 h after injection. 51Cr-EDTA data were used to evaluate the glomerular filtration rate (GFR) and the completeness of each timed urine collection. 125I-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: 99mTc-MDP, 58.2% (4.8%); 18F-fluoride, 36.1% (5.7%); 51Cr-EDTA, 81.5% (4.5%). Plots of the renal clearance of 18F-fluoride against urine volume showed that urine flow rates greater than 5 ml·min−1 were necessary to ensure a constant renal clearance of 18F and hence stable conditions for the evaluation of bone tracer kinetics. In contrast, a low urine flow rate had no effect on the renal kinetics of 99mTc-MDP. For MDP, the evaluation of skeletal kinetics requires 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 ratio of total 99mTc-MDP renal clearance to GFR based on the principle that free 99mTc-MDP is a GFR tracer. Between 0 and 4 h after injection, the fractional 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 99mTc-MDP was negligible, for 18F-fluoride around 30% of circulating tracer was transported in red cells. In view of the data showing the rapid transport of 18F-fluoride across the red cell membrane, bone kinetic data for 18F are more accurately reported as whole-blood clearance rather than plasma clearance.