Validation of a blood-sampling method for the measurement of Tc-99m-methylene diphosphonate skeletal plasma clearance

Quantitative studies of bone using Tc-99m-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating Tc-99m-MDP kinetics involves taking multiple blood samples and measuring total clearance (K-total) from the area under the plasma curve (AUC) and deriving bone clearance (K-bone) by subtracting glomerular filtration rate (GFR) from K-total. However, the accuracy of the AUC method is uncertain because of assumptions that the terminal exponential is reached by 2 h and that the rate constant k(4), representing the backflow of tracer from bone to plasma, is negligibly small. The aim of this study was to validate the accuracy of the AUC method by comparing K-bone values obtained by that method with those obtained by gamma-camera imaging. Methods: Seventy-one patients were injected with 600 MBq of Tc-99m-MDP. For the first 22 patients, whole-body images were acquired at 15 min and at 1, 2, 3, and 4 h after injection, whereas the remaining 49 were imaged at 15 min and at 1 and 3 h. Two-minute static images of the thighs were acquired immediately before each whole-body scan. Multiple blood samples were taken between 5 min and 4 h, and free 99mTc-MDP was measured using ultrafiltration. Two gamma-camera methods were used to evaluate Kbone: the Patlak plot method and the Brenner method, which is based on measuring soft-tissue uptake in the thighs. The soft-tissue data were also used to measure k4. Results: The soft-tissue data gave a k4 value of 0.0003 min(-1) (95% confidence interval, 0-0.0008 min(-1)). The mean (+/- SD) Tc-99m-MDP K-bone was 56.0 +/- 32.4 mL-min(-1) with the AUC method, 49.5 +/- 32.1 mL-min(-1) with the Patlak method, and 42.8 +/- 32.0 mL-min(-1) with the Brenner method. Correcting the AUC values of K-total by factors of 0.95 and 0.90 gave K-bone values in agreement with the Patlak and Brenner methods, respectively. Conclusion: Values of k4 are too small to affect values of K-bone measured using the AUC method. Correcting K-total by factors in the range of 0.90-0.95 corrects for the error in the terminal exponential and brings K-bone values measured using the AUC method into agreement with the gamma-camera results