UPTAKE OF ETHYLENEDIAMINE TETRAMETHYLENE PHOSPHONIC ACID IN NORMAL BONE AFTER MULTIPLE APPLICATIONS - A NONHUMAN PRIMATE STUDY

Palliation of bone pain in patients with bone metastases has previousl y been evaluated using Sm-153 (samarium) complexed to bone seeking eth ylenediamine tetramethylene phosphonic acid (CAS 1429-50-1, EDTMP). Re peated application of the radioligand as needed was found regressively less effective. This study questions whether EDTMP exerts a blocking function, limiting access to bone or osseous tumours with successive a dministration. The pharmacokinetics and biodistribution of Sm-153-EDTM P in the normal experimental baboon (n = 6) during three successive ap plications (6 weekly) each with two different concentrations of EDTMP (0.7 and 1.4 mg/kg b.wt.) were investigated using bone scintigraphy. S m-153-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 statistical ly assessed in each group between successive applications and between EDTMP concentrations. Partial blocking with the low EDTMP concentratio n reached statistical significance after the third application. The fi rst application of the high EDTMP concentration yielded lower uptake i n the bone than did low EDTMP pointing to blocking by the high concent ration, 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 affec t the blocking which was thus more obvious at the low EDTMP concentrat ion.