Uptake of ethylenediamine tetramethylene phosphonic acid in normal bone after multiple applications. A non-human primate study.

Palliation of bone pain in patients with bone metastases has previously been evaluated using 153Sm (samarium) complexed to bone seeking ethylenediamine tetramethylene phosphonic acid (CAS 1429-50-1, EDTMP). Repeated application of the radioligand as needed was found progressively less effective. This study questions whether EDTMP exerts a blocking function, limiting access to bone or osseous tumours with successive administration. The pharmacokinetics and biodistribution of 153Sm-EDTMP in the normal experimental baboon (n = 6) during three successive applications (6 weekly) each with two different concentrations of EDTMP (0.7 and 1.4 mg/kg b.wt.) were investigated using bone scintigraphy. 153Sm-EDTMP (111 MBq) was injected in each case and monitored for 5 h. Curves of tracer kinetics and bone to background uptake were obtained, also blood and cumulative urine curves. Comparisons were statistically assessed in each group between successive applications and between EDTMP concentrations. Partial blocking with the low EDTMP concentration reached statistical significance after the third application. The first application of the high EDTMP concentration yielded lower uptake in the bone than did low EDTMP pointing to blocking by the high concentration, but not seen with repeated applications. Continual application of high concentration EDTMP could lead to a reduced level of calcium in serum and increased parathyroid hormone levels which might trigger osteoblastic activity and bone remodelling. This would partially affect the blocking which was thus more obvious at the low EDTMP concentration.
AuthorsI C Dormehl, W K Louw, F H Schneeweiss, R Milner, G Schmitt, U Carl, S A Croft
JournalArzneimittel-Forschung (Arzneimittelforschung) Vol. 48 Issue 4 Pg. 408-14 (Apr 1998) ISSN: 0004-4172 [Print] Germany
PMID9608885 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Ligands
  • Organometallic Compounds
  • Organophosphorus Compounds
  • Radioisotopes
  • Samarium
  • samarium Sm-153 lexidronam
  • Animals
  • Bone and Bones (metabolism)
  • Chromatography, Thin Layer
  • Half-Life
  • Ligands
  • Male
  • Organometallic Compounds (metabolism, pharmacokinetics)
  • Organophosphorus Compounds (metabolism, pharmacokinetics)
  • Papio
  • Radioisotopes
  • Samarium (pharmacokinetics)
  • Tissue Distribution

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