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Validation of a Blood-Sampling Method for the Measurement of ^99mTc-Methylene Diphosphonate Skeletal Plasma Clearance

School of Medicine, King's College London, London, United Kingdom

Correspondence: For correspondence or reprints contact: Amelia E.B. Moore, PhD, Department of Nuclear Medicine, Guy's Hospital, St. Thomas St., London SE1 9RT, United Kingdom. E-mail: amelia.moore{at}kcl.ac.uk

Quantitative studies of bone using ^99mTc-methylene diphosphonate (MDP) reflect bone remodeling. The simplest method of evaluating ^99mTc-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 k₄, 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 -camera imaging. Methods: Seventy-one patients were injected with 600 MBq of ^99mTc-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 -camera methods were used to evaluate K_bone: 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) ^99mTc-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 -camera results.

Key Words: bone plasma clearance • ^99mTc-methylene diphosphonate

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				A. E.B. Moore, G. M. Blake, and I. Fogelman Quantitative Measurements of Bone Remodeling Using 99mTc-Methylene Diphosphonate Bone Scans and Blood Sampling J. Nucl. Med., March 1, 2008; 49(3): 375 - 382. [Abstract] [Full Text] [PDF]