Biospeciation, by potentiometry and computer simulation, of Sm-EDTMP, a bone tumor palliative agent.

Abstract

153Sm-EDTMP (ethylenediaminetetra(methylenephosphonic) acid) is of considerable interest as a bone therapeutic radiopharmaceutical but its properties in solution are not yet well characterized. The protonation constants of EDTMP and the formation constants of the complexes of Sm-EDTMP have accordingly been measured potentiometrically by glass electrode titrations at 25 degrees C in 0.15 M NaCl. Six protonation constants (log beta 011 = 9.638, log beta 012 = 17.330, log beta 013 = 23.597, 10g beta 014 = 28.636, log beta 015 = 31.501, log beta 016 = 32.624) and the formation constants of the [Sm(EDTMP)H-1]6-(log beta 11-1 = 4.865), [SmEDTMP]5-(log beta 110 = 12.018), [Sm(EDTMP)H]4- (log beta 111 = 17.892) and [Sm(EDTMP)H2]3- (log beta 112 = 23.437) complexes were determined. Computer simulations indicate that the [SmEDTMP]5- and the hydroxy [Sm(EDTMP)H-1]6- species are the major Sm(III) complexes formed in blood plasma, which explains the high degree of localization in the kidney and urine observed in biodistribution studies. Calcium ions are probably the major competitor for EDTMP in blood plasma. As the presence of secondary skeletal metastases results in a high rate of bone turnover, it is possible that the high concentration of calcium at these sites encourages localization of 153Sm-EDTMP.