Validation of ultrafiltration as a method of measuring free 99mTc-MDP

Quantitative studies of the kinetics of (99m)Tc-methylene diphosphonate ((99m)Tc-MDP) in metastatic and metabolic bone disease require the measurement of free tracer in plasma to derive the input function. Several methods of measuring free (99m)Tc-MDP have been described including ultrafiltration, precipitation using trichloroacetic acid, and a direct in vivo measurement based on the assumption that free MDP is cleared through the kidneys by glomerular filtration. The aim of this study was to validate ultrafiltration as a convenient and accurate method of measuring the free fraction of (99m)Tc-MDP by comparing it with the glomerular filtration rate (GFR) method. A second aim was to measure the percentage of free (99m)Tc-MDP in a cross-section of patients using ultrafiltration to determine the interpatient variability and, therefore, whether individual measurements are required for bone kinetic studies.

In study 1, 10 volunteers (7 women, 3 men; mean age, 37 y; range, 26-55 y) were injected with 3 MBq (99m)Tc-MDP and 3 MBq (51)Cr-ethylenediaminetetraacetic acid, and multiple blood and urine samples were taken between 0 and 4 h. Plasma samples were spun in 5-, 10-, and 30-kDa filters and counted in a gamma-counter. In study 2, 51 randomly selected patients (26 women, 25 men; mean age, 66 y; range, 31-87 y) attending our department for a routine bone scan were injected with 600 MBq (99m)Tc-MDP, and 4 blood samples were taken between 0 and 4 h and spun in 10-kDa filters.

In study 1, the mean percentages (+/-SD) of free (99m)Tc-MDP at 5 min and 4 h after injection measured using the 10-kDa filters were 83.1% +/- 3.4% and 44.0% +/- 10.0%. The mean ratios (+/-SEM) of the free (99m)Tc-MDP in ultrafiltrate compared with the GFR method for the 5-, 10-, and 30-kDa filters were 0.894 +/- 0.010, 0.943 +/- 0.009, and 0.987 +/- 0.010. In study 2, the mean percentages (+/-SD) of free (99m)Tc-MDP at 15 min and 4 h were 75.3% +/- 8.0% and 48.8% +/- 9.5%, with a precision error of 2.3%. The percentages of free MDP at 150 min and 4 h were significantly correlated with GFR but not with serum albumin.

Ultrafiltration provides an accurate method of evaluating free (99m)Tc-MDP in plasma for bone kinetic studies. The results from both the healthy volunteers in study 1 and the patients in study 2 show that protein binding varied with time and showed significant differences between individuals that were partly dependent on GFR. It is thus necessary to measure individual protein binding values for bone kinetic studies.