title: Uptake of bone-seekers is solely associated with mineralisation! A study with 99mTc-MDP, 153Sm-EDTMP and 18F-fluoride on osteoblasts.
abstract: OBJECTIVE
  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 (99m)Tc-MDP, (153)Sm-EDTMP and (18)F-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 mumol of radiolabelled PPs or 25 MBq (18)F-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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Nuclear Medicine, Medical University of Vienna, AKH Wien, Waehringer Guertel 18-20, 1090 Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Toegel
authors.forename: Oskar
authors.initials: O
authors.lastname: Hoffmann
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Wadsak
authors.forename: Dagmar
authors.initials: D
authors.lastname: Ettlinger
authors.forename: Leonhard-Key
authors.initials: LK
authors.lastname: Mien
authors.forename: Karoline
authors.initials: K
authors.lastname: Wiesner
authors.forename: Joseph
authors.initials: J
authors.lastname: Nguemo
authors.forename: Helmut
authors.initials: H
authors.lastname: Viernstein
authors.forename: Kurt
authors.initials: K
authors.lastname: Kletter
authors.forename: Robert
authors.initials: R
authors.lastname: Dudczak
authors.forename: Markus
authors.initials: M
authors.lastname: Mitterhauser
mesh_terms: D000327:Adsorption; D000818:Animals; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000502:physiology*; D002113:Calcification, Physiologic / Q000502:physiology*; D002478:Cells, Cultured; D003198:Computer Simulation; D005462:Fluorine Radioisotopes / Q000493:pharmacokinetics*; D008657:Metabolic Clearance Rate; D051379:Mice; D008954:Models, Biological; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D009943:Organophosphorus Compounds / Q000493:pharmacokinetics*; D010006:Osteoblasts / Q000000981:diagnostic imaging* / Q000378:metabolism*; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals / Q000493:pharmacokinetics; D013669:Technetium Tc 99m Medronate / Q000493:pharmacokinetics*
chemical_list: D005462:Fluorine Radioisotopes; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D019275:Radiopharmaceuticals; C061972:samarium Sm-153 lexidronam; D013669:Technetium Tc 99m Medronate