Abstract
Purpose
Although polyphosphonates (PPs) were introduced as bone imaging agents in nuclear medicine in the early 1970s, the mechanisms involved in their uptake still remain unclear. Suggested mechanisms range from mineral adsorption with disputed binding to the organic phase, over incorporation into the mineralisation process to a combination of both mechanisms. Thus, our investigations aimed to: (1) evaluate adsorption parameters of 99mTc-MDP, 153Sm-EDTMP and 18F-fluoride on mineralising osteoblast cultures, (2) correlate the radiotracer binding measured in the cell cultures with binding values from our previously presented mineral model and (3) compare binding with cell number.
Methods
Primary osteoblasts were obtained by sequential digestion of foetal mice calvariae. The cells were incubated with 0.3 μmol of radiolabelled PPs or 25 MBq 18F-fluoride for 120 min. Gamma signals from labelled samples were detected with a Millennium Hawkeye SPECT camera or with a dedicated Advance full-ring PET scanner and the binding percentages were calculated.
Results
From days 8 to 15 of culture, the percent binding of all evaluated tracers increased significantly, whereas the protein concentration showed insignificant changes. Additional comparisons of the binding values with our recently published pre-vivo model revealed remarkable agreement, suggesting solely bone-forming minerals to be responsible for radiotracer binding.
Conclusion
This study provides evidence that binding of the evaluated radiotracers is not associated with osteoblast numbers but only with the concentration of bone-forming minerals. The presented correlations substantiate our recently presented pre-vivo model for the evaluation of bone-seekers: mechanisms associated with the uptake of bone-seekers are irreversible and mineral-associated processes.
References
Subramanian G, McAfee JG, Rosenstreich M, Coco M. Indium-113m-labeled polyfunctional phosphonates as bone-imaging agents. J Nucl Med 1975;16:1080–4
Francis MD, Ferguson DL, Tofe AJ, Bevan JA, Michaels SE. Comparative evaluation of three diphosphonates: in vitro adsorption (C-14 labeled) and in vivo osteogenic uptake (Tc-99m complexed). J Nucl Med 1980;21:1185–9
Kanishi D. 99mTc-MDP accumulation mechanisms in bone. Oral Surg Oral Med Oral Pathol 1993;75:239–46
Schwartz Z, Shani J, Soskolne WA, Touma H, Amir D, Sela J. Uptake and biodistribution of technetium-99m-MD32P during rat tibial bone repair. J Nucl Med 1993;34:104–8
Horiuchi-Suzuki K, Konno A, Ueda M, Fukuda Y, Nishio S, Hashimoto K, et al. Skeletal affinity of Tc(V)-DMS is bone cell mediated and pH dependent. Eur J Nucl Med Mol Imaging 2004;31:388–8
Wang H, Gerbaudo VH, Hobbs LW, Spector M. Quantitation of osteoblast-like cell mineralisation on tissue culture polystyrene and Ti-6Al-4V alloy disks by Tc-99m-MDP labelling and imaging in vitro. Bone 2005;36:84–92
Mitterhauser M, Tögel S, Wadsak W, Mien L-K, Eidherr H, Wiesner K, et al. Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with [111In], [99mTc], [153Sm] and [188Re] on bone compartments: a new model for the pre vivo-evaluation of bone seekers? Bone 2004;34:835–44
Füger B, Mitterhauser M, Wadsak W, Ofluoglu S, Traub T, Karanikas G, et al. Bone lesion detection with carrier added Tc-99m EDTMP in comparison to Tc-99m DPD. Nucl Med Commun 2004;25:361–5
Mitterhauser M, Toegel S, Wadsak W, Mien LK, Eidherr H, Kletter K, et al. Binding studies of [18F]-fluoride and polyphosphonates radiolabelled with [99mTc], [111In], [153Sm] and [188Re] on bone compartments: verification of the pre-vivo model? Bone 2005;37:404–12
Marsh ME, Munne AM, Vogel JJ, Cui Y, Franceschi RT. Mineralization of bone-like extracellular matrix in the absence of functional osteoblasts. J Bone Miner Res 1995;10:1635–43
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Toegel, S., Hoffmann, O., Wadsak, W. et al. Uptake of bone-seekers is solely associated with mineralisation! A study with 99mTc-MDP, 153Sm-EDTMP and 18F-fluoride on osteoblasts. Eur J Nucl Med Mol Imaging 33, 491–494 (2006). https://doi.org/10.1007/s00259-005-0026-x
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00259-005-0026-x