- (153) Sm-amino Acid (carboxylic Acid) Complex Bone Uptake Mechanism

¹⁵³Sm-amino-phosphonates and ¹⁵³Sm-aminoacetic acids had been investigated to palliate bone cancer for many years. This paper probed into the skeletal uptake mechanism of ¹⁵³Sm, labeling with amino-acetic acids and amino-phosphonates, by studying factors that influenced the ¹⁵³Sm uptake. The whole route of ¹⁵³Sm-compounds transferred from pharmacy to inorganic phase of skeleton has been concerned. The protonation or stability constants of EDTMP, NTMP, HEDTMP, HEDP, MDP, Sm-EDTMP, Sm-NTMP, Sm-HEDTMP, Ca-HEDTMP, Mg-HEDTMP, Ni-HEDTMP and Zn-HEDTMP had been determined by potential titration, and the factors affected the preparation of Sm-coordination had been discussed. The stability constants of Ho-EDTMP and Lu-EDTMP had been computed by the free energies of Ho(Lu)-coordination and Zn-coordination. The chemical equilibrium model concerning with low weight molecules in blood has been established to analyze the essence that resulted in various bio-distribution. The studies results show that in despite of the difference of species and percentage of ¹⁵³Sm, provided as ¹⁵³Sm-EDTMP, in vivo and vitro, the major ¹⁵³Sm species existed as the form of Sm-EDTMP in vivo, when the concentrations of Sm and EDTMP were 4×10^-6 and 4×10^-7 mol/L respectively. The species and their percentages of ¹⁵³Sm were similar when the providers were ¹⁵³Sm-HEDTMP and ¹⁵³Sm-EDTMP, but there has a little ¹⁵³Sm-Citrate when the provider was ¹⁵³Sm-HEDTMP. When the provider was ¹⁵³Sm-NTMP, the ¹⁵³Sm species and their percentages were with marked distinction in vivo and in vitro, and the percentage of ¹⁵³Sm-Citrate was 25% in vivo. The percentage of ¹⁵³Sm-Citrate lowered to a neglectable level, after promoting the concentration of NTMP to 1.6×10^-4 mol/L The species of and their percentage of ¹⁷⁷Lu, provide as ¹⁷⁷Lu-EDTMP, ¹⁶⁶Ho, provide as ¹⁷⁷Lu-EDTMP were similar with ¹⁵³Sm, provided as ¹⁵³Sm-EDTMP in vitro and in vivo, and the principal species were ¹⁷⁷Lu-EDTMP and ¹⁶⁶Ho-EDTMP. Despite the percentage of ¹⁷⁷Lu-Citrate was 18%, when the concentrations of Lu and EDTMP was 4×10^-8 and 4×10^-7 mol/L respectively, the percentage of ¹⁷⁷Lu-Citrate was lower than 0.1% when the concentrations of Lu and EDTMP was 4×10^-8 and 4×10^-5 mol/L respectively. At physiological pH value, the nuclide species above were all with negative charge, so their affinity to protein and ester was neglectable and could be excreted through kidney. The principal components of ¹⁵³Sm were ¹⁵³Sm-Citrate in vivo after injection of ¹⁵³Sm-bisphophonate. Results above indicted the major factor that affected thebio-distribution of 153Sm-coordination was its stability in vivo. The adsorption behavior of 153Sm-EDTA, 153Sm-EDTMP and 153Sm3+ on HA has been discussed. The results show that Sm3+ can be adsorbed and the adsorption capacity was higher than 153Sm-coordination, and increased the [H+] or [Ca2+] will decrease the adsorption efficiency. The activity of I53Srn-EDTMP also could be adsorbed by HA, and increased the [H+] or [Ca2^] will improve its adsorption efficiency, but increased the [EDTMP] will reduce its adsorption efficiency. The activity adsorption efficiency of l53Sm-EDTA was lower than 153Sm-EDTMP, and increased the concentration of [H+] or [Ca2] can increased its adsorption efficiency slightly. Increased the [EDTA], the adsorption efficiency reduced slightly, but the increasing [PO43"j will enhance the adsorption efficiency remarkably. The activity adsorption efficiency of 153Sm-EDTA, 153Sm-NTA, 153Srn-HEDTA, 153Sm-DTPA was in inverse proportion with their stability constants at similar adsorption environment. So the activity of 153Sm-aminoacetic acids was adsorbed in the form of 153Sm3t and the activity of 1 Sm-aminophosphonates was adsorbed in the form of Sm-aminophosphonates, Computation indicated that Ca2* improved 153Sm-EDTA activity adsorption by facilitating the dissociation of 153Sm-EDTA and improved 153Sm-EDTMP activity adsorption by promoting the zeta potential of HA surface. The biological research sown that bio-distribution of 153Srn-EDTMP and the ratio of EDTMP to Sm was not correlative when the ratio between 5-300, and the bio-distribution of 153Sm-NTMP was strongly interrelated with the ratio of NTMP to Sm, the skeletal activity uptake increased with the concentration of [NTMP], and the non-target tissue activity uptake decreased with the concentration of [NTMP]. The skeletal activity uptake of 153Srn-DTPMP improved with purity of DTPMP. The bio-distributions of 153Srn-2-AEDP and 153Srn-ABDP showed the major activity was ingested by the non-target tissues. The QSAR of 153Srn-aminoacetic acids was: y = -5.21041ogK+123.0746, where, y was uptake ratio of activity by skelton (% ID) andlogKwas the stability constant of Sm-amino-acetic acids, and the QSAR of Sm-aminophosphonate was: yB = -0.014x(+34.7455, and yL=2.2884417/x2+0.001178xr 1.26801 where yBwasuptake ratio of activity by skelton( %ID -g"1), vl was uptake ratio by liver ( %ID ?g"1), Xi was molecular volume (A3) X2 was the ratio of the numbers of phosphonate and the superficial acreage of Sm-aminophosphonates (/1000 A ) .