A direct in vivo measurement of Tc-99m-methylene diphosphonate protein binding

G M Blake, A E B Moore, S J Park-Holohan, I Fogelman

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10 Citations (Scopus)

Abstract

Quantitative studies of the kinetics of Tc-99m-methylene diphosphonate (Tc-99m-MDP) in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free Tc-99m-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total Tc-99m-MDP and Cr-51-ethylenediaminetetraacetic acid (Cr-51-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free Tc-99m-MDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the whole-skeleton plasma clearance of Tc-99m-MDP (K-bone). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of Cr-51-EDTA. The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663 (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological half-life of free Tc-99m-MDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free Tc-99m-MDP (K-total = GFR+K-bone), such that a larger value of K-total was associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and K-bone. A strong inverse relationship was found between K-total and the plasma concentration of free Tc-99m-MDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow re-equilibration of bound MDP in the circulation. The results confirm that the fraction of free Tc-99m-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K-bone amongst other factors. (C) 2003 Lippincott Williams Wilkins).
Original languageEnglish
Pages (from-to)829 - 835
Number of pages7
JournalNuclear Medicine Communications
Volume24
Issue number7
DOIs
Publication statusPublished - 2003

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