title: A direct in vivo measurement of 99mTc-methylene diphosphonate protein binding.
abstract: Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-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 99mTc-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTc-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 99mTc-MDP (K(bone)). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-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 99mTc-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 99mTc-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 99mTc-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 99mTc-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K(bone) amongst other factors.
authors.affiliation: Department of Nuclear Medicine, Guy's Hospital, London, UK. glen.blake@kcl.ac.uk
authors.forename: G M
authors.initials: GM
authors.lastname: Blake
authors.forename: A E B
authors.initials: AE
authors.lastname: Moore
authors.forename: S J
authors.initials: SJ
authors.lastname: Park-Holohan
authors.forename: I
authors.initials: I
authors.lastname: Fogelman
mesh_terms: D000368:Aged; D002860:Chromium Radioisotopes / Q000097:blood / Q000493:pharmacokinetics; D003947:Diagnostic Techniques, Radioisotope; D004492:Edetic Acid / Q000097:blood* / Q000493:pharmacokinetics*; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000517:prevention & control; D011485:Protein Binding; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000097:blood / Q000493:pharmacokinetics; D013669:Technetium Tc 99m Medronate / Q000031:analogs & derivatives* / Q000097:blood* / Q000493:pharmacokinetics*
chemical_list: D002860:Chromium Radioisotopes; D019275:Radiopharmaceuticals; C024226:technetium Tc 99m hydroxymethylene diphosphonate; D004492:Edetic Acid; D013669:Technetium Tc 99m Medronate